scholarly journals Post-Transplant Cyclophosphamide (PTCy) Is Associated with Improved Clinical Outcomes in HLA-Mismatched Unrelated Donor (MMUD) Hematopoietic Stem Cell Transplantation (HCT). The University of Miami Experience

2021 ◽  
Vol 27 (3) ◽  
pp. S238-S239
Author(s):  
Antonio M Jimenez Jimenez ◽  
Muhammad Husnain ◽  
Deukwoo Kwon ◽  
Lazaros J. Lekakis ◽  
Denise Pereira ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Clinical Outcomes ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
The University

Desensitization for Mismatched Hematopoietic Stem Cell Transplantation (HSCT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1955-1955 ◽  
Author(s):  
Douglas Edward Gladstone ◽  
Andrea Zachary ◽  
Ephraim J. Fuchs ◽  
Leo Luznik ◽  
Yvette L. Kasamon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hla Antigens ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Specific Antibodies ◽  
Post Transplant

Abstract Abstract 1955 Introduction: Sensitization to donor HLA antigens is associated with an increased risk of engraftment failure in HLA mismatched hematopoietic stem cell transplantation (HSCT). However, the use of partially mismatched donors is increasing since, at best, only 30% of patients have an HLA identical sibling donor available for transplantation, and many are unable to find a matched unrelated donor in a timely fashion. A non-myeloablative, T cell replete regimen for HSCT that utilizes post-transplant high dose, cyclophosphamide for graft-versus-host-disease (GVHD) prophylaxis was pioneered at Johns Hopkins and has permitted transplantation of over 200 patients with HLA-haploidentical related donors. The use of HLA haplo-identical donors greatly increases the numbers of potential donors for most HSCT candidates. Review of the evaluations of 148 consecutive candidates for haplotransplantation revealed that 95% had at least one haplo-identical donor with an average of 2.7 donors/patient. However donor specific HLA antibody (DSHA) was observed in 10.8% of patients. We report here, successful desensitization of (DHSA) to levels safe for HSCT in six broadly sensitized patients who had poor-risk hematologic malignancies and for whom there were no other donors for whom HLA specific antibodies were not an issue. Methods: The desensitization protocol was modified from that developed for renal transplant patients at the Johns Hopkins University Comprehensive Transplant Center and included alternate day, single volume plasmapheresis (PP) with low dose, 100mg/kg, anti-CMV hyper immune immunoglobulin (IVIg) under immunosuppression with tacrolimus and mycophenolate mofetil. Varying numbers of PP/IVIg treatments were scheduled prior to the non-myeloablative conditioning regimen according to each patient's DHSA level. PP/IVIg was stopped during conditioning. All but one patient received one additional PP/IVIg at transplant day −1. HLA antibodies were assessed by solid phase immunoassays using panels of pooled HLA antigens, HLA phenotypes, and single HLA antigens in microbead suspension array immunoassays (GenProbe Lifecodes Inc., San Diego, CA; One Lambda, Inc., Canoga Park, CA) Results and conclusions: All six patients prior to desensitization had DHSA at levels sufficient to yield positive flow cytometric crossmatch (FCXM) tests defined as 12K molecules of equivalent soluble fluorochromes (MESFs). The donor specific antibodies were reduced to levels well below a positive FXCM in all six patients by the end of the PP/IVIG treatments and before transplantation through an average of 4.2 PP/IVIg treatments. The average reduction in the donor specific antibody strength was 71.5% (range: 52–91%). In three patients, the DHSA levels were reduced to negative by time of transplant. A fourth patient was transplanted with a DHSA level just below that consistent with a positive FCXM, but by three months post-transplant had completely eliminated the DHSA. Two patients received one additional post-transplant PP/IVIg, resulting in stable DSA levels well below a +FCXM. Sufficient post-transplant follow-up of more than four months was available for four patients of which 3 received grafts from haploidentical donors and 1 from an HLA-mismatched unrelated donor. All four of these fully engrafted with no acute GVHD episodes. These results demonstrate that desensitization can extend the opportunity for HSCT to sensitized patients with no other donor options. Disclosures: Luznik: Otsuka Pharmaceuticals: Research Funding.

scholarly journals Molecular Monitoring in Acute Myeloid Leukemia Patients Undergoing Matched Unrelated Donor: Hematopoietic Stem Cell Transplantation

2020 ◽  
Author(s):  
Irina Panovska-Stavridis
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Acute Myeloid

Minimal residual disease (MRD) in acute myeloid leukemia (AML) is a complex, multi-modality assessment and much as its clinical implications at different points are extensively studied, it remains even now a challenging area. It is the disease biology that governs the modality of MRD assessment; in patients harboring specific molecular targets, high sensitivity techniques can be applied. In AML patients undergoing allogenic hematopoietic stem cell transplantation (alloHSCT), relapse in considered as leading cause for treatment failure. In post-transplant setting, regular MRD status assessment enables to identify patients at risk of impending relapse when early therapeutic intervention may be beneficent. We analyzed data of AML patients who underwent matched unrelated donor (MUD) HSCT since the introduction of this procedure in the Republic of North Macedonia. Chimeric fusion transcripts were identified in three patients; two of them positive for RUNX-RUNX1T1 transcript and one for CBFB-MYH11. One patient harbored mutation in the transcription factor CCAAT/enhancer binding protein α (CEBPA). Post-transplant MRD kinetics was measured by quantitative polymerase chain or multiplex fluorescent-PCR every three months after the transplantation during the first two years after the transplant. MRD negativity was achieved in three patients by the sixth month of HSCT, who were pre-transplant MRD positive. They sustained hematological and molecular remission for 19, 9 and 7 months, respectively. The forth patient died due to transplant-related complication. Our experience suggests, when molecularly-defined AML patients undergo HSCT, regular MRD monitoring helps predict impending relapse and direct future treatment strategies.

scholarly journals Haploidentical Hematopoietic Stem-Cell Transplantation in Adults

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Salem Alshemmari ◽  
Reem Ameen ◽  
Javid Gaziev
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
T Cell Depletion ◽  
Hematopoietic Stem

Haploidentical hematopoietic stem-cell transplantation is an alternative transplant strategy for patients without an HLA-matched donor. Still, only half of patients who might benefit from transplantation are able to find an HLA-matched related or unrelated donor. Haploidentical donor is readily available for many patients in need of immediate stem-cell transplantation. Historical experience with haploidentical stem-cell transplantation has been characterised by a high rejection rate, graft-versus-host disease, and transplant-related mortality. Important advances have been made in this field during the last 20 years. Many drawbacks of haploidentical transplants such as graft failure and significant GVHD have been overcome due to the development of new extensive T cell depletion methods with mega dose stem-cell administration. However, prolonged immune deficiency and an increased relapse rate remain unresolved problems of T cell depletion. New approaches such as partial ex vivo or in vivo alloreactive T cell depletion and posttransplant cell therapy will allow to improve immune reconstitution in haploidentical transplants. Results of unmanipulated stem-cell transplantation with using ATG and combined immunosuppression in mismatched/haploidentical transplant setting are promising. This paper focuses on recent advances in haploidentical hematopoietic stem-cell transplantation for hematologic malignancies.

scholarly journals Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation

Microbiome ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Anna Cäcilia Ingham ◽  
Katrine Kielsen ◽  
Malene Skovsted Cilieborg ◽  
Ole Lund ◽  
Susan Holmes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Side Effects ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Clinical Outcomes ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Immune Reconstitution ◽  
Immune Markers ◽  
Hematopoietic Stem

Abstract Background Increasing evidence reveals the importance of the microbiome in health and disease and inseparable host-microbial dependencies. Host-microbe interactions are highly relevant in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), i.e., a replacement of the cellular components of the patients’ immune system with that of a foreign donor. HSCT is employed as curative immunotherapy for a number of non-malignant and malignant hematologic conditions, including cancers such as acute lymphoblastic leukemia. The procedure can be accompanied by severe side effects such as infections, acute graft-versus-host disease (aGvHD), and death. Here, we performed a longitudinal analysis of immunological markers, immune reconstitution and gut microbiota composition in relation to clinical outcomes in children undergoing HSCT. Such an analysis could reveal biomarkers, e.g., at the time point prior to HSCT, that in the future could be used to predict which patients are of high risk in relation to side effects and clinical outcomes and guide treatment strategies accordingly. Results In two multivariate analyses (sparse partial least squares regression and canonical correspondence analysis), we identified three consistent clusters: (1) high concentrations of the antimicrobial peptide human beta-defensin 2 (hBD2) prior to the transplantation in patients with high abundances of Lactobacillaceae, who later developed moderate or severe aGvHD and exhibited high mortality. (2) Rapid reconstitution of NK and B cells in patients with high abundances of obligate anaerobes such as Ruminococcaceae, who developed no or mild aGvHD and exhibited low mortality. (3) High inflammation, indicated by high levels of C-reactive protein, in patients with high abundances of facultative anaerobic bacteria such as Enterobacteriaceae. Furthermore, we observed that antibiotic treatment influenced the bacterial community state. Conclusions We identify multivariate associations between specific microbial taxa, host immune markers, immune cell reconstitution, and clinical outcomes in relation to HSCT. Our findings encourage further investigations into establishing longitudinal surveillance of the intestinal microbiome and relevant immune markers, such as hBD2, in HSCT patients. Profiling of the microbiome may prove useful as a prognostic tool that could help identify patients at risk of poor immune reconstitution and adverse outcomes, such as aGvHD and death, upon HSCT, providing actionable information in guiding precision medicine.

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