scholarly journals Haploidentical Stem Cell Transplantation: A Gateway to Infrequent Availability of HLA-Matched Related Donors

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Hafiz Muhammad Aslam ◽  
Shumaila Muhammad Iqbal ◽  
Hira Shaikh ◽  
Faizan A. Faizee ◽  
Ambreen A. Merchant ◽  
...  

Haploidentical stem cell transplantation provides a plausible alternative for the patients when a fully matched donor is unavailable. Historically, the decision of considering haploidentical transplant has remained elusive; however, with the recent advances, the consideration of haploidentical grafts as a treatment option has become more apparent for both allografting for diseases and engraftment failure. We are reporting here an anecdotal case of a successful haploidentical engraftment in a patient with the prior graft failure of an HLA-matched related donor. Since the patient was severely alloimmunized, desensitization protocol was utilized before the haploidentical transplant, and the patient after 8 months of her second allogeneic transplantation is doing great with successful engraftment, no relapse, and no graft-versus-host disease (GVHD). Numerous reports pertinent to haploidentical graft have shown favorable outcomes in the graft placement, a decline in the rate of GVHD, and an improvement in the morbidity and mortality in affected individuals. Based on the current reports, haploidentical transplantation might be more feasible and has meaningful implications in the situations where matched donors are infrequent.

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao-Hua Luo ◽  
Ying-Jun Chang ◽  
Xiao-Jun Huang

Cytomegalovirus (CMV) infection and delayed immune reconstitution (IR) remain serious obstacles for successful haploidentical stem cell transplantation (haplo-SCT). CMV-specific IR varied according to whether patients received manipulated/unmanipulated grafts or myeloablative/reduced intensity conditioning. CMV infection commonly occurs following impaired IR of T cell and its subsets. Here, we discuss the factors that influence IR based on currently available evidence. Adoptive transfer of donor T cells to improve CMV-specific IR is discussed. One should choose grafts from CMV-positive donors for transplant into CMV-positive recipients (D+/R+) because this will result in better IR than would grafts from CMV-negative donors (D−/R+). Stem cell source and donor age are other important factors. Posttransplant complications, including graft-versus-host disease and CMV infection, as well as their associated treatments, should also be considered. The effects of varying degrees of HLA disparity and conditioning regimens are more controversial. As many of these factors and strategies are considered in the setting of haplo-SCT, it is anticipated that haplo-SCT will continue to advance, further expanding our understanding of IR and CMV infection.


Immunotherapy ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 635-640
Author(s):  
Konstantinos Gkirkas ◽  
Maria Stamouli ◽  
Angeliki Karagiannidou ◽  
Spyros Chondropoulos ◽  
Panagiotis Tsirigotis

Background: Relapse is a significant cause of treatment failure after allogeneic stem cell transplantation. In many cases relapse occurs when leukemic cells escape from immune surveillance. Methods & results: In the setting of haploidentical transplantation, immune escape is usually the result of the loss of the mismatched haplotype from leukemic cells, while downregulation of HLA-expression has been postulated as a significant cause of immune escape after transplantation with the use of HLA-matched donors. We observed that patients with acute leukemia who relapse at the time of active graft-versus-host-disease, usually develop extramedullary leukemia while they remain free of leukemia in peripheral blood and bone marrow. Conclusion: Our observation points toward a novel mechanism of immune escape which is microenvironment-specific.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1419-1419 ◽  
Author(s):  
Kai Hübel ◽  
Olaf Weingart ◽  
Frauke Naumann ◽  
Julia Bohlius ◽  
Keith Wheatley ◽  
...  

Abstract Abstract 1419 Poster Board I-442 For more than 20 years high dose chemotherapy followed by allogeneic stem cell transplantation (SCT) has been considered as a reasonable approach for the treatment of patients with AML. Moreover, during the last decade new scientific and technical developments results in major changes of clinical practice of transplantation. Enhanced donor availabilities and new strategies, e.g. dose-reduced conditioning, now make allogeneic stem cell transplantation available to patients who do not have a related donor or would not tolerate high-dose chemotherapy due to age or comorbidities. Usually, the decision to start the work-up process for allogeneic transplantation in AML patients is based on the availability of a donor, the assignment to the cytogenetic risk group, and the response to induction therapy, as well as patient factors. However, there would be greater confidence in defining who should, or should not, receive an allograft if the available recommendations given in guidelines are consistent and similar. In this analysis, a comprehensive systematic literature search for best available evidence from controlled clinical trials was performed in the bibliographic databases MEDLINE, EMBASE and Cochrane Central. In addition, the websites of major organizations in Europe and the US (European Group for Blood and Marrow Transplantation, EBMT; European Society for Medical Oncology, ESMO; British Committee for Standards in Hematology, BCSH; American Society for Blood and Marrow Transplantation, ASBMT; National Comprehensive Cancer Network, NCCN) were screened and the specific databases of the National Guideline Clearinghouse and the Guideline International Network Database were also searched to identify the latest recommendations and guidelines. The following points were selected for systematic comparison of the best available evidence: Factors for risk assessment and categorization of AML, donor categories for allogeneic SCT (sibling donors / matched unrelated donors), allogeneic transplantation in first CR, allogeneic transplantation in relapse/progressive disease or second CR, and allogeneic transplants with reduced intensity conditioning regimen. Several interesting findings emerge from this analysis: 1) For patients with relapse or refractory disease donor availability should be explored and discussed, though this is not based on reliable evidence from randomized studies; 2) Patients in CR1 with intermediate or high risk disease who have a matched related donor available should receive allogeneic stem cell transplantation (intermediate risk; ASBMT: reasonable, NCCN: option); 3) For patients who lack a family donor the recommendations are not consistent; 4) Allogeneic transplantation with reduced conditioning in AML patients is feasible, but the superiority over standard therapeutic regimens has not been proven yet. In summary, current guidelines differ in critical points in the recommendation for allogeneic stem cell transplantation. Furthermore, it is likely that only well-defined subgroups of AML patients will benefit from stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4529-4529
Author(s):  
Yamin Tan ◽  
Huarui Fu ◽  
Yi Luo ◽  
Xiujin Ye ◽  
Li Li ◽  
...  

Abstract Abstract 4529 Engraftment failure is a rare but life-threatening complication of hematopoietic stem cell transplantation. The treatment of this condition is often challenging. We firstly reported haploidentical donor stem cells transplantation resulted in hematological reconstitution and long-time disease-free survival in a patient who developed engraftment failure after unrelated donor allogeneic stem cell transplantation and failure rescue treatment by re-infusion of autologous “back-up” stem cells. The 39-years-old male patient with acute myeloid leukemia(AML)-M2a achieved complete remission (CR) after one course of induction chemotherapy. He entered a lasting CR with 7 courses post-remission consolidation therapy and decided to receive unrelated donor allogeniec stem cell transplantation. In case of engraftment failure after allo-HSCT, autologous “back-up” cells were harvested after the last course chemotherapy (IDA 15 mg on days 1–2, 10 mg on day 3, Ara-c 300 mg on days 1–3, 200 mg on day 4), and mobilized with G-CSF 5 mg/kg/day for 5 days. The “back-up” cells consisting of 9.94×106/kg CD34+ cells were cryopreservated in liquid nitrogen. Fifteen months after de novo AML, the patient received a myeloablative conditioning regimen of busulfan and cyclophosphamide (busulfan 3.2 mg/kg/day on days -7 to -4, and cyclophosphamide 60 mg/kg/day on days -3 to -2), and an infusion of unrelated allogeneic peripheral stem cells from the Chinese Marrow Donor Program with a HLA-Cw allele mismatch on day 0. The graft contained 11.07×108/kg nucleated cells and 6.35×106/kg CD34+ cells. Pancytopenia was continuously observed during 28 days after transplantation and short tandem repeat-polymerase chain reaction (STR-PCR) analysis showed no donor chimera. As a rescue attempt for graft failure, cryopreservated autologous cells were re-infused on day +28. Unfortunately, pancytopenia was still continuously observed during 23 days after re-infused of “back-up” cells(51 days after unrelated transplantation), and bone marrow examination revealed severe bone marrow hypoplasia. On day +57 and +58 after unrelated transplantation, bone marrow cells containing 2.1×106/kg CD34+ stem cells and peripheral blood cells containing 2.81×106/kg CD34+ stem cells from a haploidentical donor sister (HLA matched in 5/10 alleles by high-resolution genotyping) were infused respectively after reduced-intensity conditioning with fludarabine and ATG (fludarabine 30mg/m2/d on day -5 to -1, ATG 100mg/d on day -4 to -1). Absolute neutrophil count >0.5×109/L was documented on day 12 after haploidentical transplantation. He achieved platelets count >20×109/L on day 28 after haploidentical transplantation. Twenty-nine days after haploidentical transplantation, bone marrow examination showed reconstitution and STR-PCR analysis indicated complete donor chimera. No grades III -IV aGVHD, extensive chronic GVHD, and severe infection after transplantation were observed. Recurrent bone marrow aspiration examinations showed the patient had been in CR. The patient remained alive during a 18-month follow-up after haploidentical transplantation. Our experience suggests that combined haploidentical donor BM and PBSC transplantation after Flu- and ATG-based conditioning could provide an effective therapeutic strategy for engraftment failure after unrelated allo-HSCT in adult patients. Considering the accessibility of haploidentical donors, haploidentical transplantation has the potential to act as a first-line choice for salvage therapy. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4159-4159
Author(s):  
Yi Luo ◽  
Yamin Tan ◽  
Xiaoyu Lai ◽  
Weiyan Zheng ◽  
Jimin Shi ◽  
...  

Abstract Abstract 4159 Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for hematologic malignancies. In clinical trials, a HLA-matched donor can only be found for about 50% to 60% of patients referred for HSCT which greatly limit the application of this important procedure. Haploidentical HSCT would increase the availability of donors for nearly 100% of patients. However, haploidentical HSCT may be associated with high risks of complications, such as graft rejection, severe GVHD and infection etc. Although great progress have been achieved in haploidentical HSCT based on advanced technologies and novel drugs, no study has simultaneously compared the outcomes of haploidentical, unrelated and HLA-matched related donor HSCT. Materials and Methods: In this study, 225 patients with hematologic malignancies received allo-HSCT from diffent donor sources in our center (69 with haploidentical donors, 62 with HLA-matched related donors and 94 with unrelated donors). The clinical outcomes of haploidentical HSCT cohort, unrelated donor HSCT cohort and HLA-matched related donor HSCT cohort were compared. In HLA-matched sibling and unrelated donor transplantation cohorts, patients received a same conditioning regimen consisting of intravenous busulfan 3.2 mg/kg/d on days –7 to –4, intravenous cyclophosphamide 60 mg/kg/d on days –3 to –2, and 250 mg/m2 of Me-CCNU orally on day -1. For haploidentical HSCT, conditioning regimen consisted of Ara-C (4 g/m2/d) on day -10 and -9, Bu (9.6mg/kg) on day -8, -7 and -6, Cy (1.8 g/m2/d) on day -5 and -4, Me-CCNU (250 mg/kg) on day -3, and ATG (2.5 mg/kg/d) on day -5 to -2. GVHD prophylaxis consisted of cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate while ATG (1.5 mg/kg/d) for three or four days, were added in HLA-matched or mismatched unrelated HSCT. Results: The patients receiving haploidentical HSCT experienced grades III-IV aGVHD more frequently than those receiving unrelated donor HSCT and related matched donor HSCT (24.4% vs 12% vs 2.6% respectively, p<0.05). However the incidence of cGVHD was comparable (17.8% in the haploidentical cohort vs 37.3% in the unrelated donor cohort vs 25.6% in the related matched donor cohort, p>0.05). The transplantation-related mortality (TRM) at d100 were 17.4%, 8.5% and 1.6% in the haploidentical, unrelated and related matched transplantation cohorts respectively (p<0.05). The 3-year relapse incidence were 10.1%, 15.9%, 17.7% in the haploidentical, unrelated and relate matched transplantation cohorts respectively (p>0.05). The 3- year overall survival (OS) was comparable in three cohorts (64.2±6.4% in the haploidentical cohort vs 67.5±5.3% in the unrelated donor cohort vs 77.5±5.8% in the related matched cohort, p>0.05). Conclusion: Although a higher incidence of aGVHD and TRM was observed in the haploidentical transplantation cohort, the incidences of cGVHD and relapse were comparable in the haploidentical, unrelated and related matched transplantation cohorts. Ultimately the patients receiving haploidentical transplantation achieved comparable OS with those receiving unrelated donor transplantation. An HLA-matched HSCT is commonly the preferred transplantation and donors from HLA-matched related siblings are usually the first choice. Haploidentical stem cell transplantation is relatively safe and efficient for patients who do not have HLA matched donors. Disclosures: No relevant conflicts of interest to declare.


2008 ◽  
Vol 83 (8) ◽  
pp. 630-634 ◽  
Author(s):  
Naoko Murashige ◽  
Masahiro Kami ◽  
Shin-ichiro Mori ◽  
Yuta Katayama ◽  
Kazuhiko Kobayashi ◽  
...  

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