scholarly journals Immune reconstitution after T-cell replete HLA haploidentical hematopoietic stem cell transplantation using high-dose post-transplant cyclophosphamide

2021 ◽  
Vol 61 (1) ◽  
pp. 1-9
Author(s):  
Yoshinobu Maeda
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Immune Reconstitution ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Post Transplant

Case Report: Haploidentical Stem Cell Transplantation In a 78 Year-Old Patient

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5468-5468
Author(s):  
Thiago Xavier Carneiro ◽  
André Domingues Pereira ◽  
Theodora Karnakis ◽  
Celso Arrais Rodrigues
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract An older chronologic age has been a consistent predictor of poor outcomes in hematopoietic stem cell transplantation (HSCT), mainly due to non-relapse mortality (NRM). Therefore, non-curative treatment strategies are commonly adopted for these patients. However, mortality and treatment toxicity has decreased as a result of improved supportive measures, such as reduced intensity conditioning regimens and optimized infection management. T-cell replete haploidentical HSCT emerged as a feasible alternative for leukemia patients without substantial differences in outcomes when compared to fully matched related donor. We report an old adult woman treated with haploidentical HSCT. A 78 year-old female patient presented with anemia, leukocytosis, thrombocytopenia and blasts in the peripheral blood. Diagnosis of acute myelogenous leukemia was established. Conventional cytogenetic demonstrated chromosome eight trisomy, and FISH was negative for other common MDS/AML cytogenetic abnormalities. FLT3-ITD and NPM1 mutations were negative. Her medical history was negative except for heavy smoking. Considering the patients advanced age, the first attending physician chose not to administer intensive treatment and started on decitabine 20 mg/m2 for 5 days. She was refractory to the first-line treatment with persistent cytopenias and blasts in the peripheral blood four weeks after treatment was started. Comprehensive geriatric assessment was performed. She was considered independent for Basic Activities of Daily Living (ADL score 6) and Instrumental Activities of Daily Living (IADL score 27), without cognitive impairment in mini-mental state examination (MMSE score 30), at risk of malnutrition in mini nutritional assessment (MNA 9). As she was considered fit, we decided to perform high-dose chemotherapy with idarubicin and cytarabine, but, once more, the disease was refractory. A rescue regimen was attempted with high-dose cytarabine and mitoxantrone, again, with no response. After discussing pros and cons with the patient and the family, we decided to start Another regimen consisting of topotecan and high dose cytarabine immediately followed by allogeneic hematopoietic stem cell transplantation (HSCT). At day 14, she had 3% blasts in the BM aspirate a T-cell replete haploidentical HSCT using her 52 year-old son as donor and mobilized peripheral blood as stem cell source was performed. Conditioning regimen consisted of fludarabine, cyclophosphamide, TBI 2Gy and post-transplant cyclophosphamide. Graft versus host disease (GVHD) prophylaxis consisted of mycophenolate mofetil and cyclosporine. She had neutrophil engraftment with complete donor chimerism at day+15 and platelet engraftment at day+17. At day+48, she had mild (stage II) skin acute GVHD resolved with topical steroids. Cyclosporine was withdrawn at day+ 93. Due to high relapse risk, the patient was started on monthly post-transplant azacitidine 36 mg/m2. At day+100 the patient remained in complete remission, complete donor chimerism in peripheral blood and bone marrow. Functionality was preserved (ADL score 6 and IADL score 24), presented discrete cognitive impairment (MMSE 28) and malnoutrition (MNA 5). She is now at day+182, doing well and performing again all usual daily activities. To the best of our knowledge, this is the oldest patient treated with haploidentical HSCT. Post transplant cyclophosphamide as T cell depletion strategy in haploidentical HSCT is well tolerated and widely available, being therefore an excellent alternative for patients without conventional donors who require immediate transplant. Older adults with hematologic malignancies are a heterogeneous group and decisions based on chronological age alone are clearly inappropriate. Recently, geriatric assessment proved to be an important prognostic tool in acute leukemia and may be useful in HSCT. In experienced centers, haploidentical HSCT in older adults may be a safe procedure and more accurate pre-transplantation risk stratification tools should be developed. Figure 1 Timeline of main events during hematopoietic stem cell transplant. Figure 1. Timeline of main events during hematopoietic stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

scholarly journals IMMUNITY TO INFECTIONS AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION

2016 ◽  
Vol 8 ◽  
pp. 2016057 ◽  
Author(s):  
Franco Aversa ◽  
Lucia Prezioso ◽  
Ilenia Manfra ◽  
Federica Galaverna ◽  
Angelica Spolzino ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Post Transplant

The advantage of using a Human Leukocyte Antigen (HLA)-mismatched related donor is that almost every patient who does not have a HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT) has at least one family member with whom shares one haplotype (haploidentical) and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD). Advances in graft processing and in pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor. Indeed, the haplo-HSCT  has spread to centers worldwide even though some centers have preferred an approach based on T cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs), others have focused on new strategies for GvHD prevention, such as G-CSF priming of bone marrow and robust post-transplant immune suppression or post-transplant cyclophosphamide (PTCY). Today, the graft can be a megadose of T-cell depleted PBPCs or standard dose of unmanipulated bone marrow and/or PBPCs.  Although haplo-HSCT modalities are based mainly on high intensity conditioning regimens, recently introduced reduced intensity regimens (RIC)   showed promise in decreasing early transplant-related mortality (TRM), and extending the opportunity of HSCT to an elderly population with more comorbidities. Infections are still mostly responsible for toxicity and non-relapse mortality due to prolonged immunosuppression related, or not, to GVHD. Future challenges lie in determining the safest preparative conditioning regimen, minimizing GvHD and promoting rapid and more robust immune reconstitution.

scholarly journals Immune reconstitution following hematopoietic stem cell transplantation, monitoring parameters and new methods of its assessment

2002 ◽  
Vol 55 (7-8) ◽  
pp. 293-298 ◽  
Author(s):  
Svetlana Vojvodic
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Immune Reconstitution ◽  
Hematopoietic Stem ◽  
Thymic Function ◽  
New Methods

Introduction Despite engraftment and function of graft after hematopoietic stem cell transplantation severe immune suppression is a characteristic of early posttransplant period. Primary parameters contributing to posttransplant immunoincompetence include: lack of sustained transfer of donor antigen specific immunity, recapitulation of immunological ontogeny effect of graft-versus-host disease (GvHD) and its therapy and reduction of the recipient's thymic function. Normal immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT) Immune reconstitution following allogeneic HSCT depends on the age of recipient initial pathology, degree of HLA and minor histocompatibility antigen mismatches, T-cell depletion and use of anti-T-cell antibodies for conditioning and prevention of GvHD, posttransplant complications such as acute and chronic GvHD, relapse of disease and infectious status of the donor and recipient prior to transplantation. Tests for studying immune reconstitution following allogeneic transplantation most often used are cutaneous tests of delayed hypersensitivity, phenotyping of blood mononuclear cells and investigation of their functions, production of antibodies (IgG, IgM and IgA) and cytokines such as IL-2, TGF-a, TNF-a or IL-10, study of TCR, mixed leukocyte reaction toward allogeneic cells CD4/CD8 ratio and others. New tools for assessment of immune reconstitution after HSCT New methods and techniques for monitoring immune reconstitution are as follows: ELISPOT assay quantifies secretion of cytokines by T lymphocytes, analysis of the T-cell receptor (chain diversity during immune reconstitution by IMMUNOSCOPE/SPECTRATYPING method, and TREC technology that detects recent thymic emigrants in peripheral blood. Conclusion Usage of above-mentioned contemporary techniques makes it possible to assess and monitor the dynamics of immune reconstitution especially reconstitution of T-cell diversity, thymic function and antigen-specific T-cell response following HSCT.

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