-
Annals of Hematology Apr 2021A head-to-head comparison of outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning (RIC) and... (Comparative Study)
Comparative Study
Comparison of myeloablative and reduced intensity conditioning unrelated donor allogeneic peripheral blood stem cell transplant outcomes for AML using thymoglobulin for GVHD prophylaxis.
A head-to-head comparison of outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) regimens using thymoglobulin for GVHD prophylaxis is limited. We evaluated outcomes of 122 AML patients who received either busulfan (Bu)/fludarabine (Flu)/low-dose total body irradiation (TBI) as RIC (n = 64, 52%) or Bu/Flu as MAC (n = 58, 48%), and thymoglobulin 4.5 mg/kg total dose between day - 3 to - 1 for GVHD prophylaxis. Grades III-IV acute GVHD (aGVHD) was lower with Bu/Flu/TBI compared with Bu/Flu (6.2% vs 26.1%, p = 0.009). At 1 year, Bu/Flu/TBI was associated with similar chronic GVHD (41.2% vs 44.8%, p = 0.75), OS (61.9% vs 56.9%, p = 0.69), relapse rate (29.9% vs 20.7%, p = 0.24), relapse-free survival (52.8% vs 50%, p = 0.80), non-relapse mortality (17.4% vs 29.3%, p = 0.41), and GVHD-free relapse-free survival (24.2% vs 27.5%, p = 0.80) compared with Bu/Flu. Multivariable analysis did not reveal any difference in outcomes between both regimens. In summary, thymoglobulin at 4.5 mg/kg did not have any adverse impact on survival when used with RIC regimen. Both Bu/Flu/TBI and Bu/Flu conditioning regimens yielded similar survival.
Topics: Aged; Allografts; Antilymphocyte Serum; Busulfan; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Infections; Leukemia, Myeloid, Acute; Lymphocyte Depletion; Male; Middle Aged; Mycophenolic Acid; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Progression-Free Survival; Retrospective Studies; T-Lymphocytes; Tacrolimus; Transplantation Conditioning; Treatment Outcome; Unrelated Donors; Vidarabine; Whole-Body Irradiation
PubMed: 33594448
DOI: 10.1007/s00277-021-04445-8 -
Experimental Hematology Jan 2022Exposure of young C57BL/6 (B6) mice to two courses of busulfan (BSF) injections or two rounds of sublethal total-body irradiation (TBI) induced significant damage to the...
Exposure of young C57BL/6 (B6) mice to two courses of busulfan (BSF) injections or two rounds of sublethal total-body irradiation (TBI) induced significant damage to the function of hematopoietic stem and progenitor cells (HSPCs). Fifteen weeks after treatment, BSF- and TBI-treated mice had reduced white blood cells without significant change in red blood cells or platelets, indicating that BSF and TBI hematotoxicity was chronic, with leukocytes being the major targets. Hematopoietic damage induced by BSF or TBI persisted long term. Residual adverse effects were reflected by significantly decreased CD45R B cells and reduced recovery of total bone marrow cells, especially HSPCs carrying markers for KSL (KitSca-1Lin) cells, multipotent progenitor (MPP) cells (KSLCD34CD135), myeloid progenitor (MP) cells (KitSca-1Lin), and common lymphoid progenitor (CLP) cells 62 wk posttreatment. Transplantation of bone marrow (BM) cells from BSF and TBI donors at 49 weeks after treatment into lethally irradiated hosts resulted in decreased engraftment of CD45R B cells in blood and reduced reconstitution of BM HSPCs including KSL cells, short-term hematopoietic stem cells (KSLCD34CD135), MPP cells, and MP cell subsets. TBI donor had better reconstitution of CLP cells in recipients posttransplantation than did BSF donor, suggesting an impact of TBI and BSF on B cells at different development stages. In summary, BSF and TBI exposure produced long-lasting adverse effects on hematopoiesis with pronounced effects on mature B cells, immature ST-HSCs, and hematopoietic progenitor cells. Our results may have implications for therapy of human diseases.
Topics: Animals; Bone Marrow Cells; Bone Marrow Transplantation; Busulfan; Female; Hematopoiesis; Hematopoietic Stem Cells; Mice; Mice, Inbred C57BL; Myeloablative Agonists; Whole-Body Irradiation
PubMed: 34763024
DOI: 10.1016/j.exphem.2021.11.001 -
Revista Da Associacao Medica Brasileira... Oct 2016Sickle-cell diseases are the most common inherited hemoglobinopathies worldwide. Improvement in survival has been seen in the last decades with the introduction of...
Sickle-cell diseases are the most common inherited hemoglobinopathies worldwide. Improvement in survival has been seen in the last decades with the introduction of careful screening and prevention of complications and the introduction of hydroxyurea. Stem-cell transplantation is currently the only curative option for these patients and has been indicated for patients with neurological events, repeated vaso-occlusive crisis, any organ damage or presence of red blood cell antibodies. Related bone-marrow or cord-blood transplant has shown an overall survival of more than 90% with a disease-free survival of 90% in 1,000 patients transplanted in the last decades. The use of unrelated donors unfortunately has not shown the same good results, but better typing methods and improved support may improve the outcome with this source of stem cells in the future. In Brazil, only recently stem cell transplant from related donors has been included in the procedures performed in the public health system. The use of related bone marrow or cord blood and a myeloablative conditioning regimen are considered standard of care for patients with sickle-cell diseases. Transplants with non-myeloablative regimens, unrelated donors or haploidentical donors should be performed only in controlled clinical trials.
Topics: Anemia, Sickle Cell; Bone Marrow Transplantation; Brazil; Cord Blood Stem Cell Transplantation; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Myeloablative Agonists; National Health Programs; Severity of Illness Index; Transplantation Conditioning; Transplantation, Homologous
PubMed: 27982320
DOI: 10.1590/1806-9282.62.suppl1.16 -
Romanian Journal of Ophthalmology 2021Globe salvage marks the treatment success of retinoblastoma. To evaluate four treatment strategies in group D and group E retinoblastoma. Retrospective case series in...
Globe salvage marks the treatment success of retinoblastoma. To evaluate four treatment strategies in group D and group E retinoblastoma. Retrospective case series in a tertiary hospital. 81 patients with Group D and Group E retinoblastoma. Participants were divided into four sets. In set I, eyes received primary intravenous chemotherapy (IVC), cryotherapy (CT), laser therapy (LT) and Intravitreal Chemotherapy with Melphalan (IViC). In set II, primary IVC was combined with second line IVC, CT, LT and IVT-M. Set III eyes received primary IVC and Intra-arterial chemotherapy (IAC), CT, LT and IViC. Set IV eyes received IAC, CT, LT and IViC. Treatment failure was defined as inadequate response during or after IVC or IAC. globe salvage and enucleation rates. 52 eyes were included in group D and 29 in group E. In group D, globe salvage was obtained in 8 out of 11 eyes in Set I, 13 out of 19 eyes in set II, 5 out 6 eyes in set III, and 13 out of 16 eyes in set IV. In group E, enucleation was performed in 17 eyes. Global salvage was obtained in 0 out of 2 eyes in set I, 2 out of 3 eyes in set II, 3 out of 5 in set III, and in 1 out of 2 eyes in set IV. IVC with adjuvant IAC, LT, CT and IViC has shown favorable results as a treatment method for group D and group E retinoblastoma.
Topics: Adult; Combined Modality Therapy; Cryotherapy; Eye Enucleation; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Male; Melphalan; Myeloablative Agonists; Neoplasm Staging; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Salvage Therapy; Treatment Outcome
PubMed: 33817429
DOI: 10.22336/rjo.2021.5 -
American Journal of Hematology Sep 2022
HLA-matched related donor hematopoietic stem cell transplantation is a suitable treatment in adolescents and adults with sickle cell disease: Comparison of myeloablative and non-myeloablative approaches.
Topics: Adolescent; Adult; Anemia, Sickle Cell; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Myeloablative Agonists; Transplantation Conditioning
PubMed: 35802796
DOI: 10.1002/ajh.26656 -
Journal For Immunotherapy of Cancer May 2021Adoptive cell therapy with T cells genetically engineered to express a chimeric antigen receptor (CAR-T) or tumor-infiltrating T lymphocytes (TIL) demonstrates... (Comparative Study)
Comparative Study
BACKGROUND
Adoptive cell therapy with T cells genetically engineered to express a chimeric antigen receptor (CAR-T) or tumor-infiltrating T lymphocytes (TIL) demonstrates impressive clinical results in patients with cancer. Lymphodepleting preconditioning prior to cell infusion is an integral part of all adoptive T cell therapies. However, to date, there is no standardization and no data comparing different non-myeloablative (NMA) regimens.
METHODS
In this study, we compared NMA therapies with different doses of cyclophosphamide or total body irradiation (TBI) in combination with fludarabine and evaluated bone marrow suppression and recovery, cytokine serum levels, clinical response and adverse events.
RESULTS
We demonstrate that a cumulative dose of 120 mg/kg cyclophosphamide and 125 mg/m fludarabine (120Cy/125Flu) and 60Cy/125Flu preconditioning were equally efficient in achieving deep lymphopenia and neutropenia in patients with metastatic melanoma, whereas absolute lymphocyte counts (ALCs) and absolute neutrophil counts were significantly higher following 200 cGyTBI/75Flu-induced NMA. Thrombocytopenia was most profound in 120Cy/125Flu patients. 30Cy/75Flu-induced preconditioning in patients with acute lymphoblastic leukemia resulted in a minor ALC decrease, had no impact on platelet counts and did not yield deep neutropenia. Following cell infusion, 120Cy/125Flu patients with objective tumor response had significantly higher ALC and significant lower inflammatory indexes, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Receiver-operating characteristics curve analysis 7 days after cell infusion was performed to determine the cut-offs, which distinguish between responding and non-responding patients in the 120Cy/125Flu cohort. NLR≤1.79 and PLR≤32.7 were associated with clinical response and overall survival. Cytokine serum levels did not associate with clinical response in patients with TIL. Patients in the 120Cy/125Flu cohort developed significantly more acute NMA-related adverse events, including thrombocytopenia, febrile neutropenia and cardiotoxicity, and stayed significantly longer in hospital compared with the 60Cy/125Flu and TBI/75Flu cohorts.
CONCLUSIONS
Bone marrow depletion and recovery were equally affected by 120Cy/125Flu and 60Cy/125Flu preconditioning; however, toxicity and consequently duration of hospitalization were significantly lower in the 60Cy/125Flu cohort. Patients in the 30Cy/75Flu and TBI/75Flu groups rarely developed NMA-induced adverse events; however, both regimens were not efficient in achieving deep bone marrow suppression. Among the regimens, 60Cy/125Flu preconditioning seems to achieve maximum effect with minimum toxicity.
Topics: Adult; Clinical Trials, Phase II as Topic; Cyclophosphamide; Cytokines; Female; Humans; Immunotherapy, Adoptive; Length of Stay; Lymphocyte Depletion; Male; Melanoma; Middle Aged; Myeloablative Agonists; Receptors, Chimeric Antigen; Recovery of Function; Skin Neoplasms; T-Lymphocytes; Time Factors; Transplantation Conditioning; Treatment Outcome; Vidarabine; Whole-Body Irradiation
PubMed: 33990415
DOI: 10.1136/jitc-2020-001743 -
Biology of Blood and Marrow... Apr 2014Haploidentical hematopoietic stem cell transplantation (HSCT) offers the benefits of rapid and nearly universal donor availability and has been accepted worldwide as an... (Review)
Review
Haploidentical hematopoietic stem cell transplantation (HSCT) offers the benefits of rapid and nearly universal donor availability and has been accepted worldwide as an alternative treatment for patients with hematologic malignancies who do not have a completely HLA-matched sibling or who require urgent transplantation. Unfortunately, serious infections and leukemia relapse resulting from slow immune reconstitution remain the 2 most frequent causes of mortality in patients undergoing haploidentical HSCT, particularly in those receiving extensively T cell-depleted megadose CD34(+) allografts. This review summarizes advances in immune recovery after haploidentical HSCT, focusing on the immune subsets likely to have the greatest impact on clinical outcomes. The progress made in accelerating immune reconstitution using different strategies after haploidentical HSCT is also discussed. It is our belief that a predictive immune subset-guided strategy to improve immune recovery might represent a future clinical direction.
Topics: Graft Survival; HLA Antigens; Haplotypes; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Lymphocyte Depletion; Myeloablative Agonists; T-Lymphocytes; Transplantation Conditioning; Transplantation Tolerance; Transplantation, Homologous; Treatment Outcome
PubMed: 24315844
DOI: 10.1016/j.bbmt.2013.11.028 -
Biology of Blood and Marrow... Aug 2015Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much...
Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells.
Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/μL of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting.
Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Cohort Studies; Cyclophosphamide; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Sirolimus; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Young Adult
PubMed: 26001696
DOI: 10.1016/j.bbmt.2015.04.025 -
Experimental and Clinical... Feb 2019The only known curative therapy for primary myelofibrosis is allogeneic hematopoietic stem cell transplant.
OBJECTIVES
The only known curative therapy for primary myelofibrosis is allogeneic hematopoietic stem cell transplant.
MATERIALS AND METHODS
We retrospectively evaluated 11 transplant procedures involving 10 patients (5 men and 5 women) diagnosed with primary myelofibrosis between 2005 and 2014.
RESULTS
The median age at the time of transplant was 60.5 years (range, 22-62 years). Stem cell sources were unrelated (n=1) and related (n=11) peripheral blood stem cells. Conditioning regimen was myeloablative for 8 and reduced intensity for 3 transplants. The median number of infused CD34+ cells was 6.8 × 106 cells/kg (range, 3.2-10.4 × 106 cells/kg). Neutrophil and platelet engraftment occurred at median of 22 days (range, 12-31 days) and 19.5 days (range, 13-56 days). Acute and chronic graft-versus-host disease was seen in 4 of 11 allografts. Relapse and nonrelapse mortality rates were 20%. Six patients (60%) were still alive without disease after median follow-up of 68.5 months (range, 17-120 months). Median progression-free survival and overall survival were 61 months (range, 2-120 months) and 65 months (range, 2-120 months).
CONCLUSIONS
Our results suggest that allogeneic hematopoietic stem cell transplant may provide a curative treatment for primary myelofibrosis patients. A myeloablative regimen seems to be effective and safe, especially for younger primary myelofibrosis patients.
Topics: Acute Disease; Adult; Allogeneic Cells; Antigens, CD34; Chronic Disease; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Myeloablative Agonists; Primary Myelofibrosis; Progression-Free Survival; Recurrence; Retrospective Studies; Risk Factors; Time Factors; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Young Adult
PubMed: 27855592
DOI: 10.6002/ect.2016.0007 -
Biology of Blood and Marrow... Oct 2014Two parallel phase II trials in adults with hematologic malignancies demonstrated comparable survival after reduced-intensity conditioning and transplantation of either... (Review)
Review
Two parallel phase II trials in adults with hematologic malignancies demonstrated comparable survival after reduced-intensity conditioning and transplantation of either 2 HLA-mismatched umbilical cord blood (UCB) units or bone marrow from HLA-haploidentical relatives. Donor choice is often subject to physician practice and institutional preference. Despite clear preliminary evidence of equipoise between HLA-haploidentical related donor and double unrelated donor UCB transplantation, the actual prospect of being randomized between these 2 very different donor sources is daunting to patients and their treating physicians alike. Under these circumstances, it is challenging to conduct a phase III randomized trial in which patients are assigned to the UCB or haploidentical bone marrow arms. Therefore, we aimed to provide an evidence-based review and recommendations for selecting donors for adults without an HLA-matched sibling or an HLA-matched adult unrelated donor.
Topics: Bone Marrow Transplantation; Cord Blood Stem Cell Transplantation; Decision Trees; Gene Expression; HLA Antigens; Haplotypes; Hematologic Neoplasms; Histocompatibility Testing; Humans; Myeloablative Agonists; Randomized Controlled Trials as Topic; Recurrence; Siblings; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Unrelated Donors
PubMed: 24862638
DOI: 10.1016/j.bbmt.2014.05.015