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Balkan Medical Journal Jan 2017Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment option for both malignant and some benign hematological diseases. During the last... (Review)
Review
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment option for both malignant and some benign hematological diseases. During the last decade, many of the newer high-dose regimens in different intensity have been developed specifically for patients with hematologic malignancies and solid tumors. Today there are three main approaches used prior to allogeneic transplantation: Myeloablative (MA), Reduced Intensity Conditioning (RIC) and Non-MA (NMA) regimens. MA regimens cause irreversible cytopenia and there is a requirement for stem cell support. Patients who receive NMA regimen have minimal cytopenia and this type of regimen can be given without stem cell support. RIC regimens do not fit the criteria of MA and NMA: the cytopenia is reversible and the stem cell support is necessary. NMA/RIC for Allo-HSCT has opened a new era for treating elderly patients and those with comorbidities. The RIC conditioning was used for 40% of all Allo-HSCT and this trend continue to increase. In this paper, we will review these regimens in the setting of especially allogeneic HSCT and our aim is to describe the history, features and impact of these conditioning regimens on specific diseases.
Topics: Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Transplantation Conditioning; Transplantation, Homologous
PubMed: 28251017
DOI: 10.4274/balkanmedj.2017.0055 -
Scientific Reports Jul 2021In many stem cell transplant centres, BCNU, etoposide, cytarabine and melphalan (BEAM) high-dose chemotherapy (HDCT) has been replaced by the more economic and available...
In many stem cell transplant centres, BCNU, etoposide, cytarabine and melphalan (BEAM) high-dose chemotherapy (HDCT) has been replaced by the more economic and available bendamustine, etoposide, cytarabine, melphalan (BeEAM) regimen. However, there is a paucity of information on the efficacy and safety of BeEAM HDCT. We describe our experience with BeEAM HDCT in terms of safety, efficacy and cost-savings. We compare overall and progression-free survival to a cohort of patients previously transplanted at our institution with the older BEAM regimen. We performed a retrospective chart review of 41 lymphoma patients undergoing BeEAM HDCT at the Royal University Hospital in Saskatoon, Saskatchewan between 2015 and 2019 to elicit regimen safety in the first 100 days post-transplant. Furthermore, we calculated overall and progression-free survival and constructed corresponding Kaplan-Meier curves, comparing the results to a historical cohort of BEAM patients (n = 86). Finally, we conducted an economic analysis using the financials available at our centre's pharmacy. With regards to BeEAM HDCT, we report a 100-day transplant-related mortality of 2.4%. Additionally, we report acceptable rates of typhlitis (27%), grade III-IV mucositis (4.9%) and grade III-IV nephrotoxicity (2.4%). In terms of overall and progression-free survival, we found no statistical difference between BeEAM and BEAM (p = 0.296; 0.762, respectively). Finally, our economic analysis revealed a net savings of $21,200 CAD per transplant when BeEAM is used in replacement of BEAM. The acceptable safety profile of BeEAM and its comparable efficacy to BEAM are encouraging for the perseverance of this cost-effective HDCT regimen.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Neoplasms; Outcome Assessment, Health Care; Podophyllotoxin; Transplantation Conditioning
PubMed: 34234243
DOI: 10.1038/s41598-021-93516-x -
Cells Apr 2024Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been... (Review)
Review
Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25-57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia.
Topics: Humans; Leukemia, Myeloid, Acute; Transplantation, Homologous; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Graft vs Host Disease
PubMed: 38727291
DOI: 10.3390/cells13090755 -
Biology of Blood and Marrow... Mar 2019The search for the optimal conditioning regimen before allogeneic hematopoietic stem cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic...
The search for the optimal conditioning regimen before allogeneic hematopoietic stem cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) has been ongoing for decades. In this issue, Solh et al present an original analysis evaluating the impact of conditioning intensity on different disease risk index (DRI) groups of patients with AML and MDS. An impressive difference was observed in outcomes between reduced-intensity conditioning and myeloablative conditioning (MAC) regimens in the low/intermediate-risk disease groups, supporting the use of MAC in this population. Further prospective trials in this population are encouraged.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Myeloablative Agonists; Myelodysplastic Syndromes; Risk Assessment; Transplantation Conditioning; Transplantation, Homologous
PubMed: 30562588
DOI: 10.1016/j.bbmt.2018.12.067 -
Biology of Blood and Marrow... Sep 2014
Topics: Genes, T-Cell Receptor; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Transplantation Conditioning; Transplantation, Homologous
PubMed: 25016196
DOI: 10.1016/j.bbmt.2014.07.002 -
Biology of Blood and Marrow... Apr 2017Sustained donor engraftment after allogeneic hematopoietic cell transplantation (HCT) converts to healthy donor hemoglobin synthesis and halts disease symptoms in...
Current Results and Future Research Priorities in Late Effects after Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease and Thalassemia: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after...
Sustained donor engraftment after allogeneic hematopoietic cell transplantation (HCT) converts to healthy donor hemoglobin synthesis and halts disease symptoms in patients with sickle cell disease and thalassemia major. A disease-free survival probability that exceeds 90% has been reported when HCT using an HLA-matched sibling donor is performed in young patients with low-risk disease or treatment-related risk factors. Alternate donor HCT and HCT in adults is performed infrequently because of a higher risk profile. Transplant-specific risks include conditioning regimen-related toxicity, graft-versus-host disease, graft rejection with marrow aplasia or disease recurrence, and infections associated with immunosuppression and delayed immune reconstitution. The magnitude of risk depends on patient age, clinical status of the underlying disease (eg, organ injury from vasculopathy and iron overload), donor source, and intensity of the conditioning regimen. These risks are commonly monitored and reported in the short term. Documenting very late outcomes is important, but these data are rarely reported because of challenges imposed by patient drop-out and insufficient resources. This report summarizes long-term follow-up results after HCT for hemoglobin disorders, identifies gaps in knowledge, and discusses opportunities for future investigations. This consensus summary will be followed by a second article detailing comprehensive long-term follow-up recommendations to aid in maintaining health in these individuals and identifying late complication risks that could facilitate interventions to improve outcomes.
Topics: Anemia, Sickle Cell; Child; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Risk Factors; Thalassemia; Time Factors; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous
PubMed: 28065838
DOI: 10.1016/j.bbmt.2017.01.009 -
Biology of Blood and Marrow... Dec 2012Haploidentical hematopoietic stem cell transplant (HSCT) provides an opportunity for nearly all patients to benefit from HSCT. We conducted a trial of haploidentical T...
Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial.
Haploidentical hematopoietic stem cell transplant (HSCT) provides an opportunity for nearly all patients to benefit from HSCT. We conducted a trial of haploidentical T cell replete allografting using a busulfan-based myeloablative preparative regimen, peripheral blood stem cells (PBSCs) as the graft source, and posttransplantation cyclophosphamide (Cy). Eligibility was limited to patients at high risk of relapse after nonmyeloablative haploidentical bone marrow transplant (BMT). Twenty patients were enrolled in the study (11 with relapsed/refractory disease and 9 who underwent transplantation while in remission and considered standard risk). Donor engraftment occurred in all 20 patients with full donor T cell and myeloid chimerism by day +30. The cumulative incidence of grades II-IV and III-IV acute graft-versus-host disease (aGVHD) was 30% and 10%, respectively. The cumulative incidence of chronic GVHD (cGVHD) was 35%. Nonrelapse mortality (NRM) at 100 days and 1 year was 10% for all patients and 0% for standard-risk patients. With a median follow-up of 20 months, the estimated 1-year overall survival (OS) and disease-free survival (DFS) was 69% and 50%, respectively, for all patients, and 88% and 67% for standard-risk patients. Myeloablative haploidentical HSCT is associated with excellent rates of engraftment, GVHD, NRM, and DFS, and is a valid option in patients with high-risk malignancies who lack timely access to a conventional donor.
Topics: Adult; Disease-Free Survival; Graft vs Host Disease; Haplotypes; Hematologic Neoplasms; Humans; Middle Aged; Peripheral Blood Stem Cell Transplantation; Prospective Studies; T-Lymphocytes; Transplantation Chimera; Transplantation Conditioning
PubMed: 22863841
DOI: 10.1016/j.bbmt.2012.06.019 -
Biology of Blood and Marrow... Feb 2016This report describes hematopoietic cell transplantation (HCT) activity and outcome in Australia and New Zealand during the years 2005 to 2013. In 2013, 1018 autologous,... (Review)
Review
This report describes hematopoietic cell transplantation (HCT) activity and outcome in Australia and New Zealand during the years 2005 to 2013. In 2013, 1018 autologous, 221 allogeneic with related donors, and 264 allogeneic with unrelated donors HCT were performed in 40 centers in Australia, with corresponding figures of 147, 39, and 47 in 6 centers in New Zealand. Annual numbers of HCT in 2013 increased, compared to 2005, by 25% in Australia and by 52% in New Zealand. The majority of both allogeneic and autologous HCT used peripheral blood as the stem cell source for all years studied. Major indications for transplantation were acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), plasma cell disorders, and non-Hodgkin lymphoma (NHL). Overall survival probabilities at 5 years after transplantation for adult (16+) allogeneic first HCT recipients were 54.2% for ALL, 46.0% for AML, 48.4% for myelodysplastic syndromes, and 58.6% for NHL. Consistent patterns over time include a steady increase in HCT, particularly for older recipients, relatively constant numbers of allografts using cord blood, and a recent increase in the number of allografts with 2 or more HLA-mismatched related donors.
Topics: Adolescent; Adult; Aged; Australia; Child; Child, Preschool; Hematopoietic Stem Cell Transplantation; History, 21st Century; Humans; Infant; Middle Aged; New Zealand; Transplantation Conditioning; Young Adult
PubMed: 26385524
DOI: 10.1016/j.bbmt.2015.09.009 -
Biology of Blood and Marrow... Aug 2011As success of reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) relies primarily on graft-versus-leukemia (GVL) activity, increased... (Comparative Study)
Comparative Study
Use of matched unrelated donors compared with matched related donors is associated with lower relapse and superior progression-free survival after reduced-intensity conditioning hematopoietic stem cell transplantation.
As success of reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) relies primarily on graft-versus-leukemia (GVL) activity, increased minor HLA disparity in unrelated compared to related donors could have a significant impact on transplant outcomes. To assess whether use of unrelated donors (URD) engenders more potent GVL in RIC HSCT compared to matched related donors (MRD), we retrospectively studied 433 consecutive T-replete 6/6 HLA matched URD (n = 246) and MRD (n = 187) RIC HSCT for hematologic malignancies at our institution. Diseases included: acute myelogenous leukemia (AML) (127), non-Hodgkin lymphoma (NHL) (71), chronic lymphocytic leukemia (CLL) (68), myelodysplastic syndrome (MDS) (64), Hodgkin disease (HD) (40), chronic myeloid leukemia (CML) (25), multiple myeloma (MM) (23), myeloproliferative disorder (MPD) (12), acute lymphoblastic leukemia (ALL) (7), and other leukemia (1). All received uniform fludarabine and intravenous busulfan conditioning, and GVHD prophylaxis with tacrolimus/mini-methroxate (mini-MTX) or tacrolimus/sirolimus ± mini-MTX. Unrelated donors were younger compared to MRD (median donor age: 33 years versus 52 years, P < .0001), and provided larger CD34(+) products (median CD34(+) cells infused: 8.7 × 10(6)/kg versus 7.5 × 10(6)/kg, P = .002). Distribution of diseases, disease risk, prior transplant, and cytomegalovirus (CMV) status was similar in both cohorts. Cumulative incidence of grade II-IV acute GVHD (at day +180), 2-year chronic GVHD, and 2-year nonrelapse mortality (NRM) were 20% versus 16%, 55% versus 50%, and 8% versus 6% in URD and MRD, respectively (P = NS). Cumulative incidence of relapse at 2 years was lower in URD, 52% versus 65% (P = .005). With median follow-up of 26.5 and 35.8 months, 2-year progression-free survival (PFS) was significantly better in unrelated donor transplants, 39.5% for URD, and 29% for MRD (P = .01). Overall survival (OS) at 2 years were 56% for URD versus 50% for MRD (P = .53). In multivariable analysis, URD was associated with a lower risk of relapse (hazard ratio [HR] 0.67, P = .002) and superior PFS (HR 0.69, P = .002). These results suggest that URD is associated with greater GVL activity than MRD, and could have practice changing impact on future donor selection in RIC HSCT.
Topics: Adolescent; Adult; Aged; Cohort Studies; Disease-Free Survival; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Recurrence; Retrospective Studies; Tissue Donors; Transplantation Conditioning; Transplantation, Autologous; Unrelated Donors; Young Adult
PubMed: 21193054
DOI: 10.1016/j.bbmt.2010.12.702 -
Turkish Journal of Haematology :... Aug 2018The evidence-based literature on healthcare is currently expanding exponentially. The opportunities provided by the advancement in artificial intelligence (AI) tools... (Review)
Review
The evidence-based literature on healthcare is currently expanding exponentially. The opportunities provided by the advancement in artificial intelligence (AI) tools such as machine learning are appealing in tackling many of the current healthcare challenges. Thus, AI integration is expanding in most fields of healthcare, including the field of hematology. This study aims to review the current applications of AI in the field of hematopoietic cell transplantation (HCT). A literature search was done involving the following databases: Ovid MEDLINE, including In-Process and other non-indexed citations, and Google Scholar. The abstracts of the following professional societies were also screened: American Society of Hematology, American Society for Blood and Marrow Transplantation, and European Society for Blood and Marrow Transplantation. The literature review showed that the integration of AI in the field of HCT has grown remarkably in the last decade and offers promising avenues in diagnosis and prognosis in HCT populations targeting both pre- and post-transplant challenges. Studies of AI integration in HCT have many limitations that include poorly tested algorithms, lack of generalizability, and limited use of different AI tools. Machine learning techniques in HCT are an intense area of research that needs much development and extensive support from hematology and HCT societies and organizations globally as we believe that this will be the future practice paradigm.
Topics: Artificial Intelligence; Hematopoietic Stem Cell Transplantation; Humans; Transplantation Conditioning
PubMed: 29880463
DOI: 10.4274/tjh.2018.0123