HLA-haploidentical hematopoietic stem cell transplantation is now one of the most commonly employed alternative donor techniques, with most centers applying T-cell–replete strategies such as that developed by the Baltimore group using high-dose posttransplant cyclophosphamide. A similar high-dose regimen of cyclophosphamide in conjunction with transplantation was given to 90 patients with scleroderma and resulted in a 6% treatment-related mortality, with four of the five deaths during the peritransplantation period attributable to cardiac complications.35 These data suggest that high-dose cyclophosphamide may be too toxic for some patients with severe scleroderma, particularly in the presence of heart disease. Manufacture of autologous CD34+ selected grafts in the NIAID-sponsored HALT-MS and SCOT multicenter clinical trials for autoimmune diseases. Daikeler T, Tichelli A, Passweg J. and S.R.M. It reflects how participants compare with one another on the basis of a hierarchy of ordered outcomes: death, event-free survival (survival without respiratory, renal, or cardiac failure), FVC, the score on the Disability Index of the Health Assessment Questionnaire (HAQ-DI; range, 0 to 3, with higher scores indicating more disability), and the modified Rodnan skin score (Section S1 of Methods in the Supplementary Appendix). has received grant support from an American Cancer Society Institutional Research Grant. Learn about the types of stem cells and stem cell therapies available for uses in cancer treatment, bone marrow transplantation, and spinal cord injury, as well as research. 27. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. However, there are certain clinical scenarios in which a MUD or an HLA-mismatched unrelated donor (MMUD) is preferred. This article was selected by the Blood and Hematology 2019 American Society of Hematology Education Program editors for concurrent submission to Blood and Hematology 2019. Arthritis Rheumatol 2016;68:2361-2371. Thank you for submitting a comment on this article. Lisa Marie Thompson, Pharm.D., Maria Estela Ceja, Pharm.D., BCOP, Sonal Patel Yang, Pharm.D., BCPS, Stem cell transplantation for treatment of sickle cell disease: Bone marrow versus cord blood transplants, American Journal of Health-System Pharmacy, Volume 69, Issue 15, 1 August 2012, Pages 1295–1302, https://doi.org/10.2146/ajhp110308. Stat Med 1999;18:1341-1354. After an event of respiratory, renal, or cardiac failure occurred (i.e., event-free survival was not achieved), clinic visits ended but telephone contacts continued to month 54. S3 in the Supplementary Appendix). The prognosis of patients with hypoplastic myelodysplastic syndrome (hMDS) after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. Register, Oxford University Press is a department of the University of Oxford. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. Our early clinical data suggest that second HSCT is associated with a 4-year OS of 40%; however, longer survival was demonstrated when the second donor had a distinct haplotype mismatch from the initial HSCT donor.71  Our practice is to try DLI first, especially for early relapses, which could potentially be related to insufficient graft dose or incomplete immune reconstitution and reserve second HSCT for cases for DLI failure. Categorical data analysis using the SAS system. Besides genomic loss of mismatched HLA alleles, downregulation of HLA class II molecules and upregulation of inhibitory T-cell ligands are likely important mechanisms of posttransplant relapse after haplo-HSCT.72  More work needs to be done to better understand the biology underlying graft-versus-tumor effects and posttransplant relapse and represents the next frontier. Understanding the impact of donor age on outcomes in haplo-HSCT is difficult, not only because of the correlation between donor and recipient age, but also because of the correlation of recipient age and donor relationship inherent to haploidentical related donors; that is, older recipients are more likely to have children or sibling donors, whereas younger recipients are more likely to have sibling or parent donors. Safety end points included treatment-related death, death from any cause, treatment-related toxic effects, infections, and hematologic engraftment. As these patients often require numerous platelet transfusions, platelet refractoriness may be encountered and practice options are discussed. P=0.01 for the comparison between treatment groups (Wilcoxon signed-rank test). Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Baseline characteristics reflected severe scleroderma: the mean modified Rodnan skin score was 30, the mean DLco was 53% of the predicted value, and 97% of the participants had pulmonary involvement (Table 1, and Table S3 in the Supplementary Appendix). 30. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. The patient discussed above received 1 cycle of high-dose cytarabine consolidation that was uncomplicated. The approach for patients who relapse after haplo-HSCT is challenging, and there are no clear guidelines. During salvage chemotherapy, we inquired regarding the availability of second-degree relatives. Other toxic effects were consistent with those in studies of transplantation in other diseases. At 13 months after HSCT, he developed systemic relapse, with BM biopsy revealing 63% myeloblasts with 49% recipient DNA. 36. van Bekkum DW. † For the global rank composite score (GRCS), P values are based on the Wilcoxon signed-rank test. Fisher’s exact test was used for dichotomous events, including death and event-free survival at 54 and 48 months; the Mantel–Haenszel chi-square test was used for stratified analysis. The stem cell transplant process begins with conditioning or preparative regimens, tailored to optimize stem cell harvesting. allogeneic stem cell transplant, myelofibrosis, idiopathic, chronic, allogeneic hematopoietic stem cell transplant Abstract Allogeneic hematopoietic stem cell transplantation (SCT) is the only curative option for patients with primary myelofibrosis (PMF), but information on its net advantage over conventional therapies is lacking. Although survival outcomes, including relapse, after haplo-HSCT and HLA-matched HSCT appear to occur at similar rates, it is important to recognize that a distinct immune mechanism with significant clinical implications, called “HLA loss,” occurs in 30% of acute myeloid leukemia (AML) relapses after haplo-HSCT.16-18  The present article discusses a complicated case of one patient with AML to review what we have learned in the last decade of research and describes the authors’ personal approach to haplo-HSCT with PTCy. ‡ Deaths after 54 months were not counted in the primary end-point analyses. Organ failure refers to respiratory, renal, or cardiac failure. Thus, clinical investigation of new desensitization platforms for patients with the highest levels of DSA (positive for either flow cross-match or complement dependent cytotoxicity) is warranted. As such, for patients with MRD in whom additional pretransplantation therapy is not pursued, we prefer allografting with PBSCTs and/or for early cessation of immunosuppression, which was associated with less relapse in a small study of BM allografts.62  In addition, a clinical trial using maintenance therapies (eg, enasidenib, ivosidenib, idelalisib, gilteritinib, blinatumomab, venetoclax, and APR-246) or prophylactic posttransplantation immunotherapy (donor lymphocyte or natural killer cell infusion) to prevent relapse should be considered in these high-risk patients. When a transplant is successful, the donor stem cells can replace stem cells in the bone marrow. P=0.06 for sex, 0.39 for smoking status, and 0.06 for previous use of cyclophosphamide. Further molecular studies confirmed HLA loss.17  The patient underwent salvage chemotherapy with mitoxantrone, etoposide, and cytarabine and achieved a second CR with MRD negativity by flow cytometry. ; Jones, J.M. His pretransplant BM showed CR without MRD. Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T cells and restoring the CD4+CD25+ immune regulatory network. Scales are more fully detailed in Section S1 of Methods in the Supplementary Appendix.21,22. Noninfectious fevers occur in 80% to 90% of haplo-PBSCT recipients between days 0 and 6 after transplantation. You could not be signed in. Original Article from The New England Journal of Medicine — Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma Although the global rank composite score has not been used in studies of scleroderma, similar approaches have gained acceptance in trials of other diseases.25-29 The global rank composite score is not a clinical measure but rather an analytic approach that compares every participant in a study with every other participant on the basis of a predefined hierarchy of outcomes — in this case, outcomes specific for severe scleroderma.1,4,9,12 Objective components (death, event-free survival, and FVC) were scored at a higher priority than more subjective measures (HAQ-DI score and modified Rodnan skin score). Low accrual prompted amendments, first to broaden entry criteria, then, ultimately, to reduce the sample size by changing the primary end point to the global rank composite score. Please check for further notifications by email. Clin Immunol 2004;113:285-298. * The participant had had an event of respiratory, renal, or cardiac failure before death. When using BM grafts, higher nucleated cell graft dose has been associated with improved progression-free survival and OS in haplo-HSCT with PTCy.52  Thus, at centers with less experienced harvesters, there may be an advantage to using PBSCT, which typically has less potential for yielding low-dose grafts. By continuing you agree to the use of cookies. Tashkin DP, Elashoff R, Clements PJ, et al. With the assumption that transplant recipients would have worse early outcomes but could fare better long-term than participants in the comparison group, the global rank composite score is intentionally constructed to treat early and late deaths (or events of organ failure) as equal, irrespective of timing. Our dedicated information section provides allows you to learn more about MDPI.

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