Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for Patients with Hematologic Malignancies

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation （allo-PBSCT）, 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2, The acute graft-versus host disease （aGVHD） was prevented by cyclosporin A and shortterm MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox （CD25 MAb） at dosage of 1 rag/ kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil （MMF）. Transfusion of the donor cells： The median of the transfused nucleated cells was 5.38×10^8/kg and that of the CD34^＋ cells was 7.8×10^6/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got Ⅱ°-Ⅳ° aGVHD and the incidence was 17.5 %. Fourteen patients got cGVHD and the incidence was 53.8 % in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality （TRM） was 17.5 %and 2 patients relapsed （5.0 %）. It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.

CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS FOLLOWING ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

Objective： To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis （CMV-IP） after allogeneic peripheral blood stem cell transplantation （allo-PBSCT）. Methods： 43 patients who received allo-PBSCT were allocated to either a Gancyclovir（GCV）-prophylaxis group （n=19） or a non-GCV prophylaxis group （n=24）. A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results： 9 patients in non-GCV prophylaxis group developed late CMV-IP （P〈0.05）. Graft-versus-host-disease （GVHD） may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP. The most common adverse event of GCV was neutropenia, but was reversible. Conclusion： CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.

Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma

Day 100 prognostic factors post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) to predict clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients have not been studied. Thus, we retrospectively examined if day 100 absolute monocyte/lymphocyte prognostic score (AMLPS-100) affects clinical outcomes by landmark analysis from day 100 post-APBHSCT in DLBCL. Only DLBCL patients in complete remission at day 100 post-APBHSCT were evaluated. From 2000 to 2007, 134 consecutive DLBCL patients are qualified for the study. Patients with a day 100 absolute monocyte count (AMC-100) ≥ 630 cells/μL and day 100 absolute lymphocyte count (ALC-100) ≤ 1000 cells/μL experienced inferior overall survival (OS) and progression free survival (PFS). On multivariate analysis, the AMC-100 and ALC-100 remained independent predictors of OS and PFS. Combining both values into the AMLPS-100, the 5-year OS rates for low, intermediate, and high AMLPS-100 risk groups were 94% (95% CI, 83.0% - 98.1%), 70% (95% CI, 58.6% - 80.1%), and 13% (95% CI, 3.4% - 40.5%), respectively;and the 5-year PFS rates were 87% (95% CI, 74.0% - 94.1%), 68% (95% CI, 56.0% - 77.8%), and 13% (95% CI, 3.4% - 40.5%), respectively. The AMLPS-100 is a simple biomarker score that can stratify clinical outcomes from day 100 post-APBHSCT in DLBCL patients.

Clinical Utility of Molecular Diagnosis of Blood Stream Infections in Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Hematologic Malignancies

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.

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center

Anaplastic large-cell lymphoma(ALCL) is characterized by frequently presenting adverse factors at diagnosis.Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients.However,few compared these approaches with conventional chemotherapy to validate their superiority.Here,we report a study comparing the efficacy of peripheral blood stem cell transplantation(PBSCT) and conventional chemotherapy on ALCL.A total of 64 patients with primary systemic ALCL were studied retrospectively.The median follow-up period was 51 months(range,1-167 months).For 48 patients undergoing conventional chemotherapy only,the 4-year event-free survival(EFS) and overall survival(OS) rates were 70.7% and 88.3%,respectively.Altogether,16 patients underwent PBSCT,including 11 at first remission(CR1/PR1),3 at second remission,and 2 with disease progression during first-line chemotherapy.The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%,respectively.Compared with conventional chemotherapy,PBSCT did not show superiority either in EFS(P = 0.240) or in OS(P = 0.580) when applied at first remission.Univariate analysis showed that patients with B symptoms(P = 0.001),stage III/IV disease(P = 0.008),bulky disease(P = 0.075),negative anaplastic lymphoma kinase(ALK) expression(P = 0.059),and age ≤ 60 years(P = 0.054) had lower EFS.Furthermore,PBSCT significantly improved EFS in patients with B symptoms(100% vs.50.8%,P = 0.027) or bulky disease(100% vs.52.8%,P = 0.045) when applied as an up-front strategy.Based on these results,we conclude that,for patients with specific adverse factors such as B symptoms and bulky disease,PBSCT was superior to conventional chemotherapy in terms of EFS.

TSR:A User-friendly R Shiny Application for Assessment of Optimal Blood Product Selection in ABO-incompatible Hematopoietic Stem Cell Transplantation

Objective:Patients undergoing hematopoietic stem cell transplant(HSCT)need frequent transfusions,until their red blood cells(RBCs)and platelets start to recover.The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process.To date,there is no user-friendly tool to choose the right blood product for transfusion treatment,despite the number of guidelines and expert advice on the subject.Methods:R/shiny is a powerful programming language for clinical data analysis and visualization.It can create interactive web applications that work in real-time.The web application named TSR was built using R programming,simplifying blood transfusion practice for ABO-incompatible HSCT witha one-click solution.Results:The TSR is divided into four main tabs.The home tab provides an overview of the application,while RBC,plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category.Unlike traditional methods that rely on treatment guidelines and specialist consensus,TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters,providing an innovative approach to improve transfusion support.Conclusion:The present study highlights that the TSR enables real-time analysis,and promotes transfusion practice byoffering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT.TSR has the potential to become a widely-utilized tool for transfusion services,providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.

How old is too old? In vivo engraftment of human peripheral blood stem cells cryopreserved for up to 18 years-implications for clinical transplantation and stability programs

BACKGROUND Peripheral blood stem cells(PBSC)are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant.Long term cryopreservation is commonly defined as five years or longer,and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft.Clinical programs,stem cell banks,and regulatory and accrediting agencies interested in product stability would benefit from such data.Thus,we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2 Rγnull(NSG)mice.AIM To investigate the in vivo engraftment potential of long-term cryopreserved PBSC units.METHODS PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University Health.These units were thawed in the Cellular Therapy Laboratory using clinical standards of practice,and the pre-freeze and post-thaw characteristics of the units were compared.Progenitor function was assessed using standard colony-forming assays.CD34-selected cells were transplanted into immunodeficient mice to assess stem cell function.RESULTS Ten PBSC units with mean of 17 years in cryopreservation(range 13.6-18.3 years)demonstrated a mean total cell recovery of 88%±12%(range 68%-110%)and post-thaw viability of 69%±17%(range 34%-86%).BFU-E growth was shown in 9 of 10 units and CFU-GM growth in 7 of 10 units post-thaw.Immunodeficient mice were transplanted with CD34-selected cells from four randomly chosen PBSC units.All mice demonstrated long-term engraftment at 12 wk with mean34%±24%human CD45+cells,and differentiation with presence of human CD19+,CD3+and CD33+cells.Harvested bone marrow from all mice demonstrated growth of erythroid and myeloid colonies.CONCLUSION We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice,signifying likely successful clinical transplantation of PBSC following long-term cryopreservation.

The safety of autologous peripheral blood stem cell transplantation by intracoronory infusionin in patients with acute myocardial infarction

Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with AMI, but the safety of intracoronory infusion of autologous peripheral blood stem-cell(PBSCs) in patients with AMI is unknown. For this reason, we observe the feasibility and safety of PBSCs transplantation by intracoronory infusion in such patients.Method Fourty one patients with AMI were allocated to receive Granulocyte Colony-Stimulating Factor (G-CSF:Filgrastim,300 μg) with the dose of 300 μg-600 μg/day to mobilize the stem cell, and the duration of applying G-CSF was 5 days . On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then the suspend liquid was infused into the infarct related artery (IRA)by occluding the over the wire balloon and infusing artery through balloon center lumen. In the process of the intracoronary infusion of PBSCs, the complications should be observed, which were arrhythmias including of bradycardia, sinus arrest or atrial ventricular block, premature ventricular beats ,ventricular tachycardia, ventricular fibrillation; and hypotention, etc. Results There were total 10 cases with complications during the intracoronary infusion of PBSCs. The incidence of complications was 24.4%(10/41), including bradycardia is 2.4 %(1/41), sinus arrest or atrial ventricular block is 4.9%(2/41), ventricular fibrillation is 2.4 %( 1/41), hypotention is14.6 % (6 /41).Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.

The Safety of Autologous Peripheral Blood Stem Cell Transplantation by Intracoronory Infusion in Patients with Acute Myocardial Infarction

Objectives Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with acute myocardial infarction (AMI) , but the safety of intracoronory infusion of autologous peripheral blood stem-cell (PBSCs) in patients with AMI is unknown. For this reason, we observe the feasibility and safety of PBSCs transplantation by intracoronory infusion in such patients. Methods 41 patients with AMI were allocated to receive granulocyte colony-stimulating factor (G- CSF: Filgrastim,300μg) with the dose of 300μg~ 600μg/day to mobilize the stem cell, and the duration of applying G-CSF was 5 days. On the sixth day, PBSCs were separated by Baxter CS 3000 blood cel 1 separator into suspend liquid 57 ml. Then the suspend liquid was infused into the infarct related artery (IRA) by occluding the over the wire balloon and infusing artery through balloon center lumen. In the process of the intracoronary infusion of PBSCs, the complications should be observed, which were arrhythmias including of bradycardia, sinus arrest or atrial ventricular block, premature ve. ntricular beats ,ven~icular tachycardia, ventricular fibrillation; and hypotention, etc. Results There were total 10 cases with complications during the intracoronary infusion of PBSCs. The incidence of complications was 24.4% (10/41), including bradyca- rdia was 2.4 % (1/41), sinus arrest or atrial ventri- cular block was 4.0% (2/41), ventricular fibrillation was 2.4 % (1/41), hypotention was 14.6 % (6/41). Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.

Optimal stem cell source for allogeneic stem cell transplantation for hematological malignancies

Hematopoietic stem cell transplant(HSCT) is a standard treatment for many hematological malignancies.Three different sources of stem cells, namely bone marrow(BM), peripheral blood stem cells(PBSC) and cord blood(CB) can be used for HSCT, and each has its own advantages and disadvantages. Randomized controlled trials(RCTs) suggest that there is no significant survival advantage of PBSC over BM in Human Leukocyte Antigen-matched sibling transplant for adult patients with hematological malignancies. PBSC transplant probably results in lower risk of relapse and hence better disease-free survival, especially in patients with high risk disease at the expense of higher risks of both severe acute and chronic graft-versus-host disease(GVHD).In the unrelated donor setting, the only RCT available suggests that PBSC and BM result in comparable overall and disease-free survivals in patients with hematological malignancies; and PBSC transplant results in lower risk of graft failure and higher risk of chronic GVHD.High level evidence is not available for CB in comparison to BM or PBSC. The risks and benefits of different sources of stem cells likely change with different conditioning regimen, strategies for prophylaxis and treatment of GVHD and manipulation of grafts. The recent success and rapid advance of double CB transplant and haploidentical BM and PBSC transplants further complicate the selection of stem cell source. Optimal selection requires careful weighing of the risks and benefits of different stem cell source for each individual recipient and donor. Detailed counseling of patient and donor regarding risks and benefits in the specific context of the patient and transplant method is essential for informed decision making.

Transplantation of mobilized peripheral blood mononuclear cells for peripheral arterial occlusive disease of the lower extremity

Objectives To assess the clinical efficacy,safety,and feasibility of autologous transplantation of mobilized peripheral blood mononuclear cells(PBMNCs)for patients with peripheral arterial occlusive disease(PAOD)of the lower extremity.Methods A total of 152 patients with PAOD of the lower extremity were enrolled into this non-controlled observational study from November 2003 to March 2006.All patients received subcutaneous injections of recombinant human granulocyte colony-stimulating factor(G-CSF,450-600μg/day)for 5 days in order to mobilize stem/progenitor cells;their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs.Patients were followed up for at least 12 weeks.Results At 12 weeks,primary manifestations,including lower limb pain and coldness,were significantly improved in 137(90.1%)of the patients;limb ulcers improved or healed in 46(86.8%)of the 53 patients,while 25 of the 48(47.9%)patients with limb gangrene remained steady or improved.Ankle-brachial index(ABI)improved in 33(22%)of the cases,and TcPO_(2) increased in 45(30%)of the cases.Angiography before treatment,and at 12 weeks after treatment,was performed in 10 of the patients and showed formation of new collateral vessels.No severe adverse effects or complications specifically related to cell transplantation were observed.Conclusion Autologous transplantation of G-CSF-mobilized PBMNCs might be a safe and effective treatment for lower limb ischemic disorder.

Allogeneic hematopoietic stem cell transplantation in a 3-year-old boy with congenital pyruvate kinase deficiency: A case report

BACKGROUND The understanding regarding genetic variation,pathophysiology,and complications associated with pyruvate kinase deficiency(PKD)in red blood cells has been explained largely,and supportive treatment is currently the main management strategy.Etiotropic managements,including transplantation and genome editing,supplying for substitute dugs of the pyruvate kinase,are all under research.CASE SUMMARY We herein report a 3-year-old boy with severe transfusion-dependent PKD cured by unrelated identical peripheral blood stem cell transplantation(PBSCT).Hemoglobin was corrected to a normal level by gene correction after PBSCT,with no complication related to the transplantation.CONCLUSION Hematopoietic stem cell transplantation could be a substitute for transfusiondependent PKD.

Skin Disinfection with 2% Chlorine Gluconate-Adine in Autologous Peripheral Hematopoietic Stem Cell Transplantation Patients

Background: Autologous peripheral blood hematopoietic stem cell transplantation is widely used in the treatment of malignant lymphoma. Patients are prone to infection during the transplantation immune deficiency period. There has been a lot of clinical research into how to better manage this period of vulnerability. Objective: This study aims to investigate the efficacy of 2% chlorhexidine gluconate (CHG) for skin disinfection in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) and observe any adverse reactions. Methods: A total of 106 patients receiving autologous hematopoietic stem cell transplantation from November 2019 to December 2020 in our district were selected as the control group. From January 2021 to January 2022, 106 patients with autologous hematopoietic stem cells were included in the experimental group. The control group used the immersion bath method. The experimental group was treated with an improved scrub bath method (including 3M 2% chlorhexidine gluconate medical sanitary wipes to wipe the whole skin once). Results: The bacteria-carrying rate of the improved method (37.74%) was significantly better than that of the traditional soaking method (72.64%), and the difference was statistically significant (P Conclusion: The improved bath/wipe method has a significant positive effect on skin disinfection for patients undergoing HSCT.

Allogeneic peripheral blood stem cell transplantation for leukemia

Objective To observe engraftment kinetics, the incidence and severity of graft-versus-host disease (GVHD), and clinical outcome on 40 recipients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT).Methods From June 1997 to May 1999, forty leukemia patients with a median age of 35 years underwent allo-PBSCT. PBSC were mobilized with G-CSF at a dose of 5 μg/kg s.c. every 12 hours for 5 days. A median of 7.7 (2.0 - 16.8) × 106 CD34+ cells/kg was infused into the recipients. Busulfancyclophosphamide (BU-CY) was used as the conditioning regimen. All patients received cyclosporine A and either methotrexate ( n = 34) or methylprednisolone ( n = 6) for GVHD prophylaxis.Results Engraftment of neutrophils and platelets was achieved at a median of 13 days (9- 28 days) and 12 days (7- 60 days) respectively. Patients receiving ≥4×106 CD34+ cells/kg or given G-CSF post transplant had significantly accelerated neutrophil and platelet engraftment. Acute GVHD occurred in 17 of 40 patients (42.5％), with grade Ⅱ-Ⅳ acute GVHD in 10 patients (25％). Chronic GVHD developed in 21 (9 extensive, 12 limited) out of 30 evaluable patients (21/30, 70％) with a median follow up of 380 days (180-900 days). Transplant related mortality was 17.5％ end the relapse rate was 10％. The probability of leukemia free survival at 3 years was 72.5％.Conclusion Allo-PBSCT can provide rapid hematopoietic reconstitution without an increased incidence of acute GVHD, but may be associated with a high risk of chronic GVHD.

Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies

Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatmentrelated toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental preclinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase Ⅱ trials that will be summarized in this review.

Autologous peripheral blood stem cell transplantation in the patients with hematologic malignancies and solid tumors

Objective To evaluate the long-term therapeutic effects of autologous peripheral blood stem cell transplantation (auto-PBSCT) on the treatment of hematological and solid tumors.Methods Fifty-one patients were recruited in this auto-PBSCT study, in which several potentially important parameters were studied including the optimal time for stem cell collection, the dose of stem cell reinfusion, the time of hematopoietic reconstitution, the disease free survival (DFS) and overall survival (OS), complications related to transplantation, and maintenance chemotherapy after auto-PBSCT.Results After APBSCT, 3-year and 5-year survival rates of NHL were 83.3%; those of AML were 74.7%; those of MM were 37.9% and 19%; those of ALL were 40% and 0% respectively. Hematopoietic reconstitution was greatly promoted by granulocyte colony stimulating factor (G-CSF). The mean time for patients' neutrophil to recover up to >0.5×109/L after APBSCT was 11.14 days in the group of the patients receiving G-CSF in contrast to 17.6 days in the group receiving no G-CSF. The most common complications of transplantation were fever, liver dysfunction and hypokalaemia, which were curable. No death was due to transplantation related complications.Conclusion Comparing with conventional chemotherapy, our study suggests that auto-PBSCT is a very important therapeutic option that can significantly improve the prognosis in the patients with hematological and solid tumors, especially in the patients with AML and NHL.

Efficacy and Safety of Unmanipulated Haploidentical Related Donor AIIogeneic Peripheral Blood Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Background： Studies of haploidentical-related donor （HRD） stem cell transplantation using a combination of peripheral blood stem cells （PBSCs） and bone marrow as the graft have reported encouraging results for patients with hematological diseases. However, few studies specifically reported transplantation of only PBSCs from HRDs among patients with relapsed or refractory acute myeloid leukemia （AML）. Here, the long-term outcomes and side effects of unmanipulated HRD PBSC transplantation （HRD-PBSCT） for relapsed/refractory AML were analyzed. Methods： We performed a retrospective analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT from HRDs （n = 36）. Results： Thirty-one （86.1%） patients in the HRD-PBSCT group achieved platelet recovery. The cumulative incidence of acute graft-versus-host disease （aGVHD） in the HRD-PBSCT group was 40.00%, and the cumulative incidence of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD-PBSCT group had recurrent disease at a median of 183 days after transplantation （range： 10-1700 days）, reaching cumulative incidences of relapse of 50.28% at 5 years. On multivariate analysis, donor age and patient age 〉40 years were independent risk factors for inferior disease-free survival or overall survival （P 〈 0.05）. The results of the present study demonstrate rapid and complete neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT under myeloablative conditioning when no matched sibling donor is available. Conclusions： Our results support the feasibility, effectiveness, and tolerability of PBSCs as a graft source in unmanipulated HRD transplantation under myeloablative conditioning in patients with leukemia.

Impact of Human Leukocyte Antigen Loci and Haplotypes on Intestinal Acute Graft-versus-host Disease after Human Leukocyte Antigen-matched Sibling Peripheral Blood Stem Cell Transplantation

Background： Acute graft-versus-host disease （aGVHD） is a common and severe complication of allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Some studies have found that the presence of certain specific human leukocyte antigen （HLA） loci could affect the occurrence of aGVHD. Meanwhile, the impact of HLA haplotypes on aGVHD has been rarely studied. This study aimed to investigate the effects of HLA loci and haplotypes on intestinal aGVHD. Methods： Totally, 345 consecutive patients undergoing first HLA-matched sibling peripheral blood stem cell transplantation （PBSCT） from February 2004 to June 2013 at Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were enrolled in this study. HLA loci and haplotypes of recipients with frequency over 5% were searched and their effects on intestinal aGVHD were investigated. Other important factors including donor age, recipient age, donor-recipient sex combinations, and conditioning regimens were also evaluated using logistic regression. Pure upper gastrointestinal tract aGVHD without diarrhea was excluded because the histological proof was unavailable. The follow-up end-point was 6 months after HSCT. Results： The cumulative incidence of intestinal aGVH D was 19.4%, with 18.0% of the patients classified as classic aGVH D and 1.4% as persistent, recurrent, or late aGVH D. Multivariate analysis showed that HLA-A31 locus （odds ratio [OR] 2.893, 95% confidence interval [CI] [1.054, 7.935], P = 0.039）, H LA B40-DR 15 （OR 3.133, 95% CI [1.250, 7.857], P = 0.015）, and HLA B46-DR9 haplotypes （OR 2,580, 95% CI l1.070, 6.220], P- 0.035）, fizmale donor for male recipient （OR 2.434, 95% （27 [1.319, 4.493], P = 0.004） were risk factors tbr intestinal aGVHD. Conclusion： The presence of certain HLA loci and haplotypes may influence the occurrence of intestinal aGVHD in PBSCT with HLA-identical sibling donors.