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      History of hematopoietic cell transplantation: challenges and progress

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      Author(s): ,
      Publication date (Electronic):
      Journal: Haematologica
      Publisher: Fondazione Ferrata Storti

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          Abstract

          After more than 60 years of research in allogeneic hematopoietic cell transplantation (HCT), this therapy has advanced from one that was declared dead in the 1960s to a standard treatment of otherwise fatal malignant and non-malignant blood diseases. To date, close to 1.5 million hematopoietic cell transplants have been performed in more than 1,500 transplantation centers worldwide. This review will highlight the enormous efforts by numerous investigators throughout the world who have brought the experimental field of HCT to clinical reality, examine ongoing challenges, and provide insights for the future.

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          Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia

          Jae H. Park, Isabelle Rivière, Mithat Gonen … (2018)
          BACKGROUND CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients. METHODS We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19–28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics. RESULTS A total of 53 adults received 19–28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden. CONCLUSIONS In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19–28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, [Related object:] NCT01044069.)
          Article 0 comments Cited 807 times – based on 0 reviews     Review now
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            Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT.

            Mohamed Sorror, Michael Maris, Rainer Storb … (2005)
            We previously reported that the Charlson Comorbidity Index (CCI) was useful for predicting outcomes in patients undergoing allogeneic hematopoietic cell transplantation (HCT). However, the sample size of patients with scores of 1 or more, captured by the CCI, did not exceed 35%. Further, some comorbidities were rarely found among patients who underwent HCT. Therefore, the current study was designed to (1) better define previously identified comorbidities using pretransplant laboratory data, (2) investigate additional HCT-related comorbidities, and (3) establish comorbidity scores that were suited for HCT. Data were collected from 1055 patients, and then randomly divided into training and validation sets. Weights were assigned to individual comorbidities according to their prognostic significance in Cox proportional hazard models. The new index was then validated. The new index proved to be more sensitive than the CCI since it captured 62% of patients with scores more than 0 compared with 12%, respectively. Further, the new index showed better survival prediction than the CCI (likelihood ratio of 23.7 versus 7.1 and c statistics of 0.661 versus 0.561, respectively, P < .001). In conclusion, the new simple index provided valid and reliable scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival. This index will be useful for clinical trials and patient counseling before HCT.
            Article 0 comments Cited 342 times – based on 0 reviews     Review now
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              Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1.

              J. H. Brown, T S Jardetzky, J C Gorga … (1993)
              The three-dimensional structure of the class II histocompatibility glycoprotein HLA-DR1 from human B-cell membranes has been determined by X-ray crystallography and is similar to that of class I HLA. Peptides are bound in an extended conformation that projects from both ends of an 'open-ended' antigen-binding groove. A prominent non-polar pocket into which an 'anchoring' peptide side chain fits is near one end of the binding groove. A dimer of the class II alpha beta heterodimers is seen in the crystal forms of HLA-DR1, suggesting class II HLA dimerization as a mechanism for initiating the cytoplasmic signalling events in T-cell activation.
              Article 0 comments Cited 299 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Haematologica
                Journal ID (iso-abbrev): Haematologica
                Journal ID (publisher-id): HAEMA
                Title: Haematologica
                Publisher: Fondazione Ferrata Storti
                ISSN (Print): 0390-6078
                ISSN (Electronic): 1592-8721
                Publication date (Electronic): 01 December 2020
                Publication date Collection: 01 December 2020
                Volume: 105
                Issue: 12
                Electronic Location Identifier: 245688
                Affiliations
                Fred Hutchinson Cancer Research Center and the University of Washington , Seattle, WA, USA
                Author notes
                Article
                DOI: 10.3324/haematol.2019.245688
                PMC ID: 7716373
                PubMed ID: 33054108
                SO-VID: 8bd26702-8383-458b-884f-03e49031380d
                Copyright © Copyright© 2020 Ferrata Storti Foundation
                License:

                This article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

                History
                Date received : 30 July 2020
                Date accepted : 25 September 2020
                Date revision received : 09 October 2020
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 182, Pages: 14
                Funding
                Support funding: This work was supported by NIH grants P01 CA078902, P30 CA015704 from the National Cancer Institute and P01 HL122173 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, which had no involvement in the study design; the collection, analysis and interpretation of data; the writing of the report; nor in the decision to submit the article for publication.
                Categories
                Subject: Centenary Review Article

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