As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements...As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.展开更多
Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes.Though remissioninduction is an important first step in the management of AML,additiona...Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes.Though remissioninduction is an important first step in the management of AML,additional treatment strategies are essential to ensure long-term disease-free survival.Recent pivotal advances in understanding the genetics and molecular biology of AML have allowed for a risk-adapted approach in its management based on relapse-risk.Allogeneic hematopoietic cell transplantation(allo-HCT)represents an effective therapeutic strategy in AML providing the possibility of cure with potent graft-versus-leukemia reactions,with a demonstrable survival advantage in younger patients with intermediate-or poor-risk cytogenetics.Herein we review the published data regarding the role of allo-HCT in adults with AML.We searched MEDLINE/PubMed and EMBASE/Ovid.In addition,we searched reference lists of relevant articles,conference proceedings and ongoing trial databases.We discuss the role of allo-HCT in AML patients stratified by cytogenetic-and molecular-risk in first complete remission,as well as allo-HCT as an option in relapsed/refractory AML.Besides the conventional sibling and unrelated donor allografts,we review the available data and recent advances for alternative donor sources such as haploidentical grafts and umbilical cord blood.We also discuss conditioning regimens,including reduced intensity conditioning which has broadened the applicability of allo-HCT.Finally we explore recent advances and future possibilities and directions of allo-HCT in AML.Practical therapeutic recommendations have been made where possible based on available data and expert opinion.展开更多
Relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic ...Relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine(DAC) for treating patients with acute lymphoblastic leukemia(ALL) who relapsed after allogeneic hematopoietic stem cell transplantation(allo-HSCT). We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission(CR), 1 achieved a partial remission(PR), and 1 had no response(NR) after treatment at the latest follow-up(LFU), the median survival was 11.2 months(range, 3.8–34, 7 months). The 1-and 2-year overall survival(OS) rates were 50%(6/12) and 25%(3/12), respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL(57.1% vs. 20%). No aggravated flares of graft-versus-host disease(GVHD) were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.展开更多
Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentiall...Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.展开更多
Determination of minimal residual disease (MRD) remains crucial for the follow-up after therapy in chronic lymphocytic leukemia (CLL) patients. Chimerism was assessed by short tandem repeat (STR)-PCR and single nucleo...Determination of minimal residual disease (MRD) remains crucial for the follow-up after therapy in chronic lymphocytic leukemia (CLL) patients. Chimerism was assessed by short tandem repeat (STR)-PCR and single nucleotide polymorphisms (SNP)-PCR, and MRD by a multicolor flow cytometric approach in 12 consecutive patients with CLL after they received allogeneic stem cell transplantation (SCT). Overall, 11 patients achieved MRD flow negativity [10 had full donor chimerism (FDC) and one had mixed chimerism (MC)]. Only one patient remained with MRD flow positivity and displayed MC. Fifty-six samples were concomitantly studied by both chimerism and MRD flow. A significant correlation was observed between MRD flow data and chimerism in both PB and BM by using a mixed effect linear regression (p < 0.001). Flow cytometry approach of MRD can be easily combined with chimerism during the follow-up post-allogeneic SCT. Both techniques appeared complementary for guiding post-transplant immunomodulation.展开更多
Blood stream infections (BSIs) are a serious problem in patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation (ASCT). We evaluated the clinical utility of molecular diagno...Blood stream infections (BSIs) are a serious problem in patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation (ASCT). We evaluated the clinical utility of molecular diagnosis for the management of BSIs in such patients. We prospectively performed a polymerase chain reaction (PCR) analysis of microbial DNA in blood samples from 10 consecutive patients with hematological malignancies at least once a week for one month after ASCT. In total, 51 and 54 samples were analyzed by bacterial and fungal PCR assays, respectively. Bacteria were detected in 24 samples from 8 patients by PCR, but in only 2 samples from one patient by blood culture. Notably, the bacteria detected in at least half of the 24 samples were considered to have originated from the oral cavity. Fungi were detected in 5 samples from 3 patients by PCR, but not by blood culture. Most cases with positive PCR results were manageable with empirical antimicrobial therapy without disclosure of DNA data. Our DNA analyses did not directly contribute to management of BSIs, but did provide valuable microbiological evidence for the patients. Additionally, oral management appears to require a critical re-evaluation to reduce the occurrence of BSIs in ASCT recipients.展开更多
Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitiv...Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation(alloHSCT) with reduced intensity conditioning(RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors. According to data from experimental animal models and preliminary clinical trials, a graft-versus-tumor(GvT) effect may also be observed in the treatment of some solid tumors(e.g., renal cell cancer, colorectal cancer, etc.) after allo-HSCT with RIC. The use of RIC regimens offers an opportunity of achieving full-donor engraftment with GvT effect, as well as, a reduced transplant-related mortality. Current literature suggests that allo-HSCT with RIC might become a choice for elderly and medically fragile patients with refractory metastatic solid tumors.展开更多
AIM To examine the optimal absolute lymphocyte count(ALC) cut-off utilizing receiver operator characteristics(ROC) in addition to graft characteristics associated with early ALC recovery.METHODS Patients who received ...AIM To examine the optimal absolute lymphocyte count(ALC) cut-off utilizing receiver operator characteristics(ROC) in addition to graft characteristics associated with early ALC recovery.METHODS Patients who received T-cell replete peripheral hematopoietic cell transplantation(HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes. RESULTS A total of 72 patients met the inclusion criteria andwere analyzed. Optimal ALC cut-off was established to be on day 14(D14) with ALC > 0.3 × 10~9/L. At 2 years, cumulative incidence of relapse was 16.9% vs 46.9%(P = 0.025) for early and delayed lymphocyte recovery cohorts, respectively. Chronic graft vs host disease was more prevalent in the early lymphocyte recovery(ELR) group at 70% vs 27%, respectively(P = 0.0006). On multivariable analysis for relapse, ELR retained its prognostic significance with HR = 0.27(0.05-0.94, P = 0.038).CONCLUSION ELR is an independent predictor for relapse in patients receiving allogeneic HCT for acute leukemia. ELR was influenced by graft characteristics particularly CD34 count.展开更多
Objective: To evaluate the significance of two-color interphase fluorescence in situ hybridization (FISH) using X and Y centromere probe in the engraftment estimation and minimal residual disease (MRD) monitoring afte...Objective: To evaluate the significance of two-color interphase fluorescence in situ hybridization (FISH) using X and Y centromere probe in the engraftment estimation and minimal residual disease (MRD) monitoring after allogeneic stem cell transplantation (alloSCT). Methods: Samples from 12 cases patients in different periods after alloSCT were detected by interphase FISH. Results: All of the 12 patients were proved to obtain engraftment 22-35 days after alloSCT. While traditional karyotype showed as 100%XX or 100%XY invariably, FISH showed different percentages of donor original sex chromosome. Conclusion: Two-color interphase FISH is a more sensitive and simple test for engraftment evaluation and MRD monitoring post SCT, though, it can not entirely replace traditional karyotype analysis and gene detection by RT-PCR.展开更多
· Porphyria cutanea tarda(PCT) with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these.Amniot...· Porphyria cutanea tarda(PCT) with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these.Amniotic membrane grafting had been performed in their patient suffering from porphyria eye disease, but necrosis developed in the grafts. Nevertheless, in our patient, allogeneic corneoscleral limbus transplantation prevented necrosis from development at corneoscleral limbus. So we considered that the allogeneic corneoscleral limbus transplantation might be an option to repair the necrosis in porphyria eye disease with avoiding sunlight and using artificial tear drops.展开更多
Stem cell-derived tissues and organs have the potential to change modern clinical science.However,rejection of allogeneic grafts by the host’s immune system is an issue which needs to be addressed before embryonic st...Stem cell-derived tissues and organs have the potential to change modern clinical science.However,rejection of allogeneic grafts by the host’s immune system is an issue which needs to be addressed before embryonic stem cell-derived cells or tissues can be used as medicines. Mismatches in human leukocyte classⅠantigens and minor histocompatibility antigens are the central factors that are responsible for various graft-versus-host diseases.Traditional strategies usually involve suppressing the whole immune systems with drugs.There are many side effects associated with these methods.Here,we discuss an emerging strategy for manipulating the central immune tolerance by naturally"introducing"donor antigens to a host so a recipient can acquire tolerance specifically to the donor cells or tissues.This strategy has two distinct stages.The first stage restores the thymic function of adult patients with sex steroid inhibitory drugs (LHRH-A),keratinocyte growth factor(KGF),interleukin 7 (IL-7)and FMS-like tyrosine kinase 3(FLT3).The second stage introduces hematopoietic stem cells and their downstream progenitors to the restored thymus by direct injection.Hematopoietic stem cells are used to introduce donor antigens because they have priority access to the thymus.We also review several clinical cases to explain this new strategy.展开更多
Objective:To discuss effect of FK506 nanospheres used at different time on the regcneration of allogeneic nerve after transplant.Methods:Single emulsion-solvent evaporation method(0/W) was adopted to prepare the FK506...Objective:To discuss effect of FK506 nanospheres used at different time on the regcneration of allogeneic nerve after transplant.Methods:Single emulsion-solvent evaporation method(0/W) was adopted to prepare the FK506 nanospheres and the tibial nerve of rats after allogeneic transplantation.FK506 nanospheres were used in group A after operation immediately,in group B in 24 h after operation,and in group C in 3 d after operation while FK506 nanospheres were not used in group D:in the 4th,8th and 12th week after operation respectively,general observation of transplanted nerves,histological examination,image analysis of myelinated fibers,wetweight determination of musculi triceps surae,retrogradely labeling of neurons by the fluorescein and electrophysiological comparison of bilateral tibial nerve were carried out.Results:FK506nanospheres can be degraded and absorbed quickly.The neural regenerations in group A and B were similar,which were both much belter than those in group C and D.The difference was statistically significant and so was the difference between group C and D.Conclusions:Drug release rate of FK506 nanospheres is accordant with the regeneration law of damaged nerves and the local application can promote the regenerations of nerves.The effect would be better if the drug is used in earlier period(within 24 h).展开更多
A new method for filling bone cavity with a graft of frozen-decalcified-defatted-driedallogeneic (FDDDA) cancellous bone was described.This method was used for the treatment of cavi-ties after the enucleation of jaw c...A new method for filling bone cavity with a graft of frozen-decalcified-defatted-driedallogeneic (FDDDA) cancellous bone was described.This method was used for the treatment of cavi-ties after the enucleation of jaw cysts in 10 patients from December 1985 to February 1990.Thewounds of 9 patients healed by first intension,but wound infection occurred in one case postopera-tively.The 9 patients,besides the patient who suffered from wound infection,were followed up for5 to 56 months,with an average of 41.1 months.Evidence of recurrence with jaw cyst.was not ob-served.展开更多
We reported 14 leukemia patients transplantedwith allogeneic peripheral blood stem cells (Allo-PBSCT)of HLA identical sibling, AML 5, ALL 4, CML 5. Therewere 12 patients in their early stage of leukemia, 2 in latestag...We reported 14 leukemia patients transplantedwith allogeneic peripheral blood stem cells (Allo-PBSCT)of HLA identical sibling, AML 5, ALL 4, CML 5. Therewere 12 patients in their early stage of leukemia, 2 in latestage. They were 32 (25-42) years old, 10 male and 4female. After conditioned with CTX and fTBI, G/GM-CSF mobilized donor’s peripheral blood mononuclearcells (MNC) 4.80 (2-46-8.43) × 108/kg and CD34+ cells3.96 (1.01-10.08) × 106 /kg were infused respectively. CSAand MTX used as GVHD prophylaxis. After Allo-PBSCT,WBC rose to 1.0 × 109 /L on day + 17 (+12 - +26) andplatelet rose to 50 x 109/L on day +27 (+19 - +35)respectively- The blood products support, the antibioticsused, and total environment protection durationdecreased. Acute GVHD presented in 7 patients (50.0o/o).Four patients died in acute GVHD and infection on daysof +73, +41 +57 and +49. The disease free survival daysafter Allo-PBSCT in the 10 patients was +137 (+91 -+240) days. It is suggested that Allo-PBSCT probably hassome advantage than that of Allo-BMT.展开更多
In order to rapidly identify the presence of hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation (AHCT) for leukemia, we developed a technique for amplifying human hypervariable minis...In order to rapidly identify the presence of hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation (AHCT) for leukemia, we developed a technique for amplifying human hypervariable minisatellite DNA by polymerase chain reaction (PCR) combined with digoxigenin-labeled locus-specific oligonucleotide hybridization. DNA fingerprinting by this technique was used as a specific genetic marker to determine the success rate of engraftment after AHCT in 7 patients with leukemia. Six of them gained evidence of engraftment. The results show that the minisatellite DNA fingerprinting is of high individual specificity and is valuable in confirming engraftment after AHCT, especially when the patient and the donor are HLA identical and of the same sex, and have the same ABO-Rh blood grouping. The advantages of this technique are that there is no contamination by radioisotopes, and its use is not restricted by the half ulife. It is simple and highly sensitive. Engraftment of donor’s hematopoietic cells can be determined as early as 15 d post-transplantation using 100 ng DNA of the patient. We conclude that this technique is highly specific and sensitive, and can rapidly provide in formation about the origin of the hematopoietic cells, thus being of value in guiding early therapeutic intervention in AHCT.展开更多
BACKGROUND Granulocytic sarcoma(GS)is a rare malignant tumor,and relapse is even rarer in the breast and dorsal spine following allogeneic hematopoietic stem cell transplantation.Currently,a standard treatment regimen...BACKGROUND Granulocytic sarcoma(GS)is a rare malignant tumor,and relapse is even rarer in the breast and dorsal spine following allogeneic hematopoietic stem cell transplantation.Currently,a standard treatment regimen is not available.CASE SUMMARY A rare case of GS of the right breast and dorsal spine after complete remission of acute myelogenous leukemia is reported here.A 55-year-old female patient presented with a palpable,growing,painless lump as well as worsening dorsal compressive myelopathy.She had a history of acute myelomonocytic leukemia(AML M4)and achieved complete remission after chemotherapy following allogeneic hematopoietic stem cell transplantation.Imaging examinations showed the breast lump and C7-T1 epidural masses suspected of malignancy.Histologic results were compatible with GS in both the right breast and dorsal spine,which were considered extramedullary relapse of the AML treated 4 years earlier.CONCLUSION A rare case of GS relapse following allogeneic hematopoietic stem cell transplantation and guidelines for treatment are discussed.展开更多
BACKGROUND Patients with paroxysmal nocturnal hemoglobinuria(PNH)have a clonal population of blood cells deficient in glycosylphosphatidylinositol-anchored(GPIanchored)proteins,most of the time resulting from a mutati...BACKGROUND Patients with paroxysmal nocturnal hemoglobinuria(PNH)have a clonal population of blood cells deficient in glycosylphosphatidylinositol-anchored(GPIanchored)proteins,most of the time resulting from a mutation in the X-linked gene PIGA.We report a patient with PNH resulting from a rare biallelic PIGT mutation on chromosome 20.CASE SUMMARY A 47-year-old man was referred to our hospital for febrile pancytopenia.The patient reported a history of recurrent urticaria and arthralgia and he presented during 3 mo recurrent acute dermo-hypodermitis and aseptic meningitidis.Based on clinical cases published with PIGT-PNH,with clinically typical PNH and autoinflammatory symptoms,we treated our patients with repeated infusions of eculizumab to decrease autoinflammatory symptoms and then we performed an allogeneic stem cell transplantation(allo-SCT)with a mismatched unrelated donor.Our patient experienced no acute Graft vs Host disease(GvHD)and a moderate chronic GvHD and is now considered cured at 24 mo after allo-SCT.CONCLUSION This case report suggests that allo-SCT should be considered to cure PIGT-PNH patients.展开更多
AIM:To evaluate the midterm outcomes of penetrating keratoplasty(PK)following allogeneic cultivated limbal epithelial transplantation(CLET)for bilateral total limbal stem cell deficiency(LSCD).METHODS:Ten patients(10 ...AIM:To evaluate the midterm outcomes of penetrating keratoplasty(PK)following allogeneic cultivated limbal epithelial transplantation(CLET)for bilateral total limbal stem cell deficiency(LSCD).METHODS:Ten patients(10 eyes)with bilateral LSCD were enrolled in this prospective noncomparative case series study.Each participant underwent PK approximately 6 mo after a CLET.Topical tacrolimus,topical and systemic steroids,and oral ciclosporin were administered postoperatively.Best-corrected visual acuity(BCVA),intraocular pressure(IOP),ocular surface grading scores(OSS),corneal graft epithelial rehabilitation,persistent epithelial defect(PED),immunological rejection,and graft survival rate were assessed.RESULTS:The time interval between PK and allogeneic CLET was 6.90±1.29(6-10)mo.BCVA improved from 2.46±0.32 log MAR preoperatively to 0.77±0.55 log MAR post-PK(P<0.001).Kaplan-Meier analysis of mean graft survival revealed graft survival rates of 100%at 12 and 24 mo and 80.0%at 36 mo.PEDs appeared in 5 eyes at different periods post-PK,and graft rejection occurred in 4 eyes.The total OSS decreased from 12.4±4.4 before allogeneic CLET to 1.4±1.51 after PK.CONCLUSION:A sequential therapy design of PK following allogeneic CLET can maintain a stable ocular surface with improved BCVA despite the relatively high graft rejection rate.展开更多
Objective This study aimed to compare the anti-tumor effects of cytokine-induced killer (CIK) cellsinduced by autologous cytokines in patients with breast cancer and those of allogeneic CIK cells fromhealthy adults.Me...Objective This study aimed to compare the anti-tumor effects of cytokine-induced killer (CIK) cellsinduced by autologous cytokines in patients with breast cancer and those of allogeneic CIK cells fromhealthy adults.Methods We used conventional methods to induce CIK cells originating from two peripheral bloodmononuclear cell types (from patients with breast cancer and healthy adults). Killing activity was detectedusing an LDH assay, immunophenotypic changes were analyzed by flow cytometry, and the IFN-γ level ofculture supernatants was detected by ELISA.Results The results showed that the proliferative capacity of the allogeneic CIK cells was significantlyhigher than that of the autologous CIK cells. Compared with autologous CIK cells, the allogeneic CIK cellshad significantly enhanced anti-tumor activity against SKBR-3 cells (P < 0.01) and IFN-γ secretion (P <0.05);moreover, they increased the ratio of CD3+ CD56+ cells and CD3+ CD8+ cells (P < 0.05).Conclusion Healthy adult-derived induced CIK cells exhibited a stronger anti-tumor effect than inducedCIK cells derived from patients with breast cancer. The results of this study could provide experimentalevidence for the clinical application of CIK cells.展开更多
AIM To examine the outcome and prognostic factors for high risk patients with acute lymphoblastic leukemia/lymphoma(ALL/LBL) who underwent allogeneic hematopoietic stem cell transplantation(HCT) at our center during t...AIM To examine the outcome and prognostic factors for high risk patients with acute lymphoblastic leukemia/lymphoma(ALL/LBL) who underwent allogeneic hematopoietic stem cell transplantation(HCT) at our center during the period of2010-2017 METHODS After due institutional review board approval, patients with high risk ALL/LBL post HCT were identified and included. All records were retrospectively collected. Time to event analysis was calculated from the date of HCT until event of interest or last follow up with Kaplan-Meir means. Cox regression model was used for multivariable analysis calculation.RESULTS A total of 69 patients were enrolled and examined with a median age of 21(14-61). After a median follow up of 15 mo(2-87.3), the 2-year cumulative incidence of relapse, cumulative incidence of non-relapse mortality, progression free survival and overall survival(OS) were 34.1%, 10.9%, 54.9% and 62.8%,respectively. In a multivariable analysis for OS; acute graft vs host disease(GVHD) and chronic GVHD were significant with corresponding hazard ratio 4.9(1.99-12; P = 0.0007) and 0.29(0.1-0.67; P = 0.0044), respectively.CONCLUSION Allogeneic-HCT for high risk ALL/LBL resulted in promising remissions particularly for patients with cGVHD.展开更多
基金Supported by the Scientific Research Project of the Sichuan Province Education Department,No. 16ZA0241the National Natural Science Foundation of China,No. 82060268the Guangxi Natural Science Foundation of China,No. 2020JJA140124。
文摘As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.
文摘Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes.Though remissioninduction is an important first step in the management of AML,additional treatment strategies are essential to ensure long-term disease-free survival.Recent pivotal advances in understanding the genetics and molecular biology of AML have allowed for a risk-adapted approach in its management based on relapse-risk.Allogeneic hematopoietic cell transplantation(allo-HCT)represents an effective therapeutic strategy in AML providing the possibility of cure with potent graft-versus-leukemia reactions,with a demonstrable survival advantage in younger patients with intermediate-or poor-risk cytogenetics.Herein we review the published data regarding the role of allo-HCT in adults with AML.We searched MEDLINE/PubMed and EMBASE/Ovid.In addition,we searched reference lists of relevant articles,conference proceedings and ongoing trial databases.We discuss the role of allo-HCT in AML patients stratified by cytogenetic-and molecular-risk in first complete remission,as well as allo-HCT as an option in relapsed/refractory AML.Besides the conventional sibling and unrelated donor allografts,we review the available data and recent advances for alternative donor sources such as haploidentical grafts and umbilical cord blood.We also discuss conditioning regimens,including reduced intensity conditioning which has broadened the applicability of allo-HCT.Finally we explore recent advances and future possibilities and directions of allo-HCT in AML.Practical therapeutic recommendations have been made where possible based on available data and expert opinion.
基金supported by grants from the National Natural Science Foundation of China(No.81300412 and No.81470333)
文摘Relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine(DAC) for treating patients with acute lymphoblastic leukemia(ALL) who relapsed after allogeneic hematopoietic stem cell transplantation(allo-HSCT). We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission(CR), 1 achieved a partial remission(PR), and 1 had no response(NR) after treatment at the latest follow-up(LFU), the median survival was 11.2 months(range, 3.8–34, 7 months). The 1-and 2-year overall survival(OS) rates were 50%(6/12) and 25%(3/12), respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL(57.1% vs. 20%). No aggravated flares of graft-versus-host disease(GVHD) were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.
文摘Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.
文摘Determination of minimal residual disease (MRD) remains crucial for the follow-up after therapy in chronic lymphocytic leukemia (CLL) patients. Chimerism was assessed by short tandem repeat (STR)-PCR and single nucleotide polymorphisms (SNP)-PCR, and MRD by a multicolor flow cytometric approach in 12 consecutive patients with CLL after they received allogeneic stem cell transplantation (SCT). Overall, 11 patients achieved MRD flow negativity [10 had full donor chimerism (FDC) and one had mixed chimerism (MC)]. Only one patient remained with MRD flow positivity and displayed MC. Fifty-six samples were concomitantly studied by both chimerism and MRD flow. A significant correlation was observed between MRD flow data and chimerism in both PB and BM by using a mixed effect linear regression (p < 0.001). Flow cytometry approach of MRD can be easily combined with chimerism during the follow-up post-allogeneic SCT. Both techniques appeared complementary for guiding post-transplant immunomodulation.
文摘Blood stream infections (BSIs) are a serious problem in patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation (ASCT). We evaluated the clinical utility of molecular diagnosis for the management of BSIs in such patients. We prospectively performed a polymerase chain reaction (PCR) analysis of microbial DNA in blood samples from 10 consecutive patients with hematological malignancies at least once a week for one month after ASCT. In total, 51 and 54 samples were analyzed by bacterial and fungal PCR assays, respectively. Bacteria were detected in 24 samples from 8 patients by PCR, but in only 2 samples from one patient by blood culture. Notably, the bacteria detected in at least half of the 24 samples were considered to have originated from the oral cavity. Fungi were detected in 5 samples from 3 patients by PCR, but not by blood culture. Most cases with positive PCR results were manageable with empirical antimicrobial therapy without disclosure of DNA data. Our DNA analyses did not directly contribute to management of BSIs, but did provide valuable microbiological evidence for the patients. Additionally, oral management appears to require a critical re-evaluation to reduce the occurrence of BSIs in ASCT recipients.
文摘Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation(alloHSCT) with reduced intensity conditioning(RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors. According to data from experimental animal models and preliminary clinical trials, a graft-versus-tumor(GvT) effect may also be observed in the treatment of some solid tumors(e.g., renal cell cancer, colorectal cancer, etc.) after allo-HSCT with RIC. The use of RIC regimens offers an opportunity of achieving full-donor engraftment with GvT effect, as well as, a reduced transplant-related mortality. Current literature suggests that allo-HSCT with RIC might become a choice for elderly and medically fragile patients with refractory metastatic solid tumors.
文摘AIM To examine the optimal absolute lymphocyte count(ALC) cut-off utilizing receiver operator characteristics(ROC) in addition to graft characteristics associated with early ALC recovery.METHODS Patients who received T-cell replete peripheral hematopoietic cell transplantation(HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes. RESULTS A total of 72 patients met the inclusion criteria andwere analyzed. Optimal ALC cut-off was established to be on day 14(D14) with ALC > 0.3 × 10~9/L. At 2 years, cumulative incidence of relapse was 16.9% vs 46.9%(P = 0.025) for early and delayed lymphocyte recovery cohorts, respectively. Chronic graft vs host disease was more prevalent in the early lymphocyte recovery(ELR) group at 70% vs 27%, respectively(P = 0.0006). On multivariable analysis for relapse, ELR retained its prognostic significance with HR = 0.27(0.05-0.94, P = 0.038).CONCLUSION ELR is an independent predictor for relapse in patients receiving allogeneic HCT for acute leukemia. ELR was influenced by graft characteristics particularly CD34 count.
文摘Objective: To evaluate the significance of two-color interphase fluorescence in situ hybridization (FISH) using X and Y centromere probe in the engraftment estimation and minimal residual disease (MRD) monitoring after allogeneic stem cell transplantation (alloSCT). Methods: Samples from 12 cases patients in different periods after alloSCT were detected by interphase FISH. Results: All of the 12 patients were proved to obtain engraftment 22-35 days after alloSCT. While traditional karyotype showed as 100%XX or 100%XY invariably, FISH showed different percentages of donor original sex chromosome. Conclusion: Two-color interphase FISH is a more sensitive and simple test for engraftment evaluation and MRD monitoring post SCT, though, it can not entirely replace traditional karyotype analysis and gene detection by RT-PCR.
文摘· Porphyria cutanea tarda(PCT) with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these.Amniotic membrane grafting had been performed in their patient suffering from porphyria eye disease, but necrosis developed in the grafts. Nevertheless, in our patient, allogeneic corneoscleral limbus transplantation prevented necrosis from development at corneoscleral limbus. So we considered that the allogeneic corneoscleral limbus transplantation might be an option to repair the necrosis in porphyria eye disease with avoiding sunlight and using artificial tear drops.
基金Supported by CHOC Children’s Foundation and CHOC Neuroscience Institute(to Li SC)NIH grant 1R21CA134391-01A1(to Zhong JF)
文摘Stem cell-derived tissues and organs have the potential to change modern clinical science.However,rejection of allogeneic grafts by the host’s immune system is an issue which needs to be addressed before embryonic stem cell-derived cells or tissues can be used as medicines. Mismatches in human leukocyte classⅠantigens and minor histocompatibility antigens are the central factors that are responsible for various graft-versus-host diseases.Traditional strategies usually involve suppressing the whole immune systems with drugs.There are many side effects associated with these methods.Here,we discuss an emerging strategy for manipulating the central immune tolerance by naturally"introducing"donor antigens to a host so a recipient can acquire tolerance specifically to the donor cells or tissues.This strategy has two distinct stages.The first stage restores the thymic function of adult patients with sex steroid inhibitory drugs (LHRH-A),keratinocyte growth factor(KGF),interleukin 7 (IL-7)and FMS-like tyrosine kinase 3(FLT3).The second stage introduces hematopoietic stem cells and their downstream progenitors to the restored thymus by direct injection.Hematopoietic stem cells are used to introduce donor antigens because they have priority access to the thymus.We also review several clinical cases to explain this new strategy.
文摘Objective:To discuss effect of FK506 nanospheres used at different time on the regcneration of allogeneic nerve after transplant.Methods:Single emulsion-solvent evaporation method(0/W) was adopted to prepare the FK506 nanospheres and the tibial nerve of rats after allogeneic transplantation.FK506 nanospheres were used in group A after operation immediately,in group B in 24 h after operation,and in group C in 3 d after operation while FK506 nanospheres were not used in group D:in the 4th,8th and 12th week after operation respectively,general observation of transplanted nerves,histological examination,image analysis of myelinated fibers,wetweight determination of musculi triceps surae,retrogradely labeling of neurons by the fluorescein and electrophysiological comparison of bilateral tibial nerve were carried out.Results:FK506nanospheres can be degraded and absorbed quickly.The neural regenerations in group A and B were similar,which were both much belter than those in group C and D.The difference was statistically significant and so was the difference between group C and D.Conclusions:Drug release rate of FK506 nanospheres is accordant with the regeneration law of damaged nerves and the local application can promote the regenerations of nerves.The effect would be better if the drug is used in earlier period(within 24 h).
文摘A new method for filling bone cavity with a graft of frozen-decalcified-defatted-driedallogeneic (FDDDA) cancellous bone was described.This method was used for the treatment of cavi-ties after the enucleation of jaw cysts in 10 patients from December 1985 to February 1990.Thewounds of 9 patients healed by first intension,but wound infection occurred in one case postopera-tively.The 9 patients,besides the patient who suffered from wound infection,were followed up for5 to 56 months,with an average of 41.1 months.Evidence of recurrence with jaw cyst.was not ob-served.
文摘We reported 14 leukemia patients transplantedwith allogeneic peripheral blood stem cells (Allo-PBSCT)of HLA identical sibling, AML 5, ALL 4, CML 5. Therewere 12 patients in their early stage of leukemia, 2 in latestage. They were 32 (25-42) years old, 10 male and 4female. After conditioned with CTX and fTBI, G/GM-CSF mobilized donor’s peripheral blood mononuclearcells (MNC) 4.80 (2-46-8.43) × 108/kg and CD34+ cells3.96 (1.01-10.08) × 106 /kg were infused respectively. CSAand MTX used as GVHD prophylaxis. After Allo-PBSCT,WBC rose to 1.0 × 109 /L on day + 17 (+12 - +26) andplatelet rose to 50 x 109/L on day +27 (+19 - +35)respectively- The blood products support, the antibioticsused, and total environment protection durationdecreased. Acute GVHD presented in 7 patients (50.0o/o).Four patients died in acute GVHD and infection on daysof +73, +41 +57 and +49. The disease free survival daysafter Allo-PBSCT in the 10 patients was +137 (+91 -+240) days. It is suggested that Allo-PBSCT probably hassome advantage than that of Allo-BMT.
文摘In order to rapidly identify the presence of hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation (AHCT) for leukemia, we developed a technique for amplifying human hypervariable minisatellite DNA by polymerase chain reaction (PCR) combined with digoxigenin-labeled locus-specific oligonucleotide hybridization. DNA fingerprinting by this technique was used as a specific genetic marker to determine the success rate of engraftment after AHCT in 7 patients with leukemia. Six of them gained evidence of engraftment. The results show that the minisatellite DNA fingerprinting is of high individual specificity and is valuable in confirming engraftment after AHCT, especially when the patient and the donor are HLA identical and of the same sex, and have the same ABO-Rh blood grouping. The advantages of this technique are that there is no contamination by radioisotopes, and its use is not restricted by the half ulife. It is simple and highly sensitive. Engraftment of donor’s hematopoietic cells can be determined as early as 15 d post-transplantation using 100 ng DNA of the patient. We conclude that this technique is highly specific and sensitive, and can rapidly provide in formation about the origin of the hematopoietic cells, thus being of value in guiding early therapeutic intervention in AHCT.
基金Supported by Youth Science Foundation of National Natural Science Foundation of China,No.81702598The Science Foundation of Guangdong Province,No.2017A030313803The Science and Technology Program of Guangzhou,No.201804010011
文摘BACKGROUND Granulocytic sarcoma(GS)is a rare malignant tumor,and relapse is even rarer in the breast and dorsal spine following allogeneic hematopoietic stem cell transplantation.Currently,a standard treatment regimen is not available.CASE SUMMARY A rare case of GS of the right breast and dorsal spine after complete remission of acute myelogenous leukemia is reported here.A 55-year-old female patient presented with a palpable,growing,painless lump as well as worsening dorsal compressive myelopathy.She had a history of acute myelomonocytic leukemia(AML M4)and achieved complete remission after chemotherapy following allogeneic hematopoietic stem cell transplantation.Imaging examinations showed the breast lump and C7-T1 epidural masses suspected of malignancy.Histologic results were compatible with GS in both the right breast and dorsal spine,which were considered extramedullary relapse of the AML treated 4 years earlier.CONCLUSION A rare case of GS relapse following allogeneic hematopoietic stem cell transplantation and guidelines for treatment are discussed.
文摘BACKGROUND Patients with paroxysmal nocturnal hemoglobinuria(PNH)have a clonal population of blood cells deficient in glycosylphosphatidylinositol-anchored(GPIanchored)proteins,most of the time resulting from a mutation in the X-linked gene PIGA.We report a patient with PNH resulting from a rare biallelic PIGT mutation on chromosome 20.CASE SUMMARY A 47-year-old man was referred to our hospital for febrile pancytopenia.The patient reported a history of recurrent urticaria and arthralgia and he presented during 3 mo recurrent acute dermo-hypodermitis and aseptic meningitidis.Based on clinical cases published with PIGT-PNH,with clinically typical PNH and autoinflammatory symptoms,we treated our patients with repeated infusions of eculizumab to decrease autoinflammatory symptoms and then we performed an allogeneic stem cell transplantation(allo-SCT)with a mismatched unrelated donor.Our patient experienced no acute Graft vs Host disease(GvHD)and a moderate chronic GvHD and is now considered cured at 24 mo after allo-SCT.CONCLUSION This case report suggests that allo-SCT should be considered to cure PIGT-PNH patients.
文摘AIM:To evaluate the midterm outcomes of penetrating keratoplasty(PK)following allogeneic cultivated limbal epithelial transplantation(CLET)for bilateral total limbal stem cell deficiency(LSCD).METHODS:Ten patients(10 eyes)with bilateral LSCD were enrolled in this prospective noncomparative case series study.Each participant underwent PK approximately 6 mo after a CLET.Topical tacrolimus,topical and systemic steroids,and oral ciclosporin were administered postoperatively.Best-corrected visual acuity(BCVA),intraocular pressure(IOP),ocular surface grading scores(OSS),corneal graft epithelial rehabilitation,persistent epithelial defect(PED),immunological rejection,and graft survival rate were assessed.RESULTS:The time interval between PK and allogeneic CLET was 6.90±1.29(6-10)mo.BCVA improved from 2.46±0.32 log MAR preoperatively to 0.77±0.55 log MAR post-PK(P<0.001).Kaplan-Meier analysis of mean graft survival revealed graft survival rates of 100%at 12 and 24 mo and 80.0%at 36 mo.PEDs appeared in 5 eyes at different periods post-PK,and graft rejection occurred in 4 eyes.The total OSS decreased from 12.4±4.4 before allogeneic CLET to 1.4±1.51 after PK.CONCLUSION:A sequential therapy design of PK following allogeneic CLET can maintain a stable ocular surface with improved BCVA despite the relatively high graft rejection rate.
基金Supported by a grant from the National Natural Sciences Foundation of Inner Mongolia(No.2012MS1102).
文摘Objective This study aimed to compare the anti-tumor effects of cytokine-induced killer (CIK) cellsinduced by autologous cytokines in patients with breast cancer and those of allogeneic CIK cells fromhealthy adults.Methods We used conventional methods to induce CIK cells originating from two peripheral bloodmononuclear cell types (from patients with breast cancer and healthy adults). Killing activity was detectedusing an LDH assay, immunophenotypic changes were analyzed by flow cytometry, and the IFN-γ level ofculture supernatants was detected by ELISA.Results The results showed that the proliferative capacity of the allogeneic CIK cells was significantlyhigher than that of the autologous CIK cells. Compared with autologous CIK cells, the allogeneic CIK cellshad significantly enhanced anti-tumor activity against SKBR-3 cells (P < 0.01) and IFN-γ secretion (P <0.05);moreover, they increased the ratio of CD3+ CD56+ cells and CD3+ CD8+ cells (P < 0.05).Conclusion Healthy adult-derived induced CIK cells exhibited a stronger anti-tumor effect than inducedCIK cells derived from patients with breast cancer. The results of this study could provide experimentalevidence for the clinical application of CIK cells.
文摘AIM To examine the outcome and prognostic factors for high risk patients with acute lymphoblastic leukemia/lymphoma(ALL/LBL) who underwent allogeneic hematopoietic stem cell transplantation(HCT) at our center during the period of2010-2017 METHODS After due institutional review board approval, patients with high risk ALL/LBL post HCT were identified and included. All records were retrospectively collected. Time to event analysis was calculated from the date of HCT until event of interest or last follow up with Kaplan-Meir means. Cox regression model was used for multivariable analysis calculation.RESULTS A total of 69 patients were enrolled and examined with a median age of 21(14-61). After a median follow up of 15 mo(2-87.3), the 2-year cumulative incidence of relapse, cumulative incidence of non-relapse mortality, progression free survival and overall survival(OS) were 34.1%, 10.9%, 54.9% and 62.8%,respectively. In a multivariable analysis for OS; acute graft vs host disease(GVHD) and chronic GVHD were significant with corresponding hazard ratio 4.9(1.99-12; P = 0.0007) and 0.29(0.1-0.67; P = 0.0044), respectively.CONCLUSION Allogeneic-HCT for high risk ALL/LBL resulted in promising remissions particularly for patients with cGVHD.
