Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy

DeFilipp, Zachariah; Advani, Anjali S.; Bachanová, Veronika; Cassaday, Ryan D.; DeAngelo, Daniel J.; Kebriaei, Partow; Rowe, Jacob M.; Seftel, Matthew D.; Stock, Wendy; Tallman, Martin S.; Fanning, Suzanne R.; Inamoto, Yoshihiro; Kansagra, Ankit; Johnston, Laura; Nagler, Arnon; Sauter, Craig S.; Savani, Bipin N.; Perales, Miguel Angel; Carpenter, Paul A.; Larson, Richard A.; Weisdorf, Daniel J.

doi:10.1016/j.bbmt.2019.08.014

Cited by 80 publications

(36 citation statements)

References 121 publications

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“…Presently, some researchers demonstrated that 3-year OS was 83% in patients who did not undergo SCT in first remission (ASH 2019), however, the current recommendation is the pursue allo-SCT for Ph + ALL (57)(58)(59). A consensus of North American experts also indicates that allo-SCT is an alternative method either for Ph+ ALL with negative pre-transplant MRD or for cases with positive pre-transplant MRD (7).…”

Section: Discussionmentioning

confidence: 99%

Different Effects of Pre-transplantation Measurable Residual Disease on Outcomes According to Transplant Modality in Patients With Philadelphia Chromosome Positive ALL

Fan

et al. 2020

Front. Oncol.

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Background: This study compared the effects of pre-transplantation measurable residual disease (pre-MRD) on outcomes in Philadelphia chromosome (Ph)-positive ALL patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical SCT (haplo-SCT). Methods: A retrospective study (n = 202) was performed. MRD was detected by RT-PCR and multiparameter flow cytometry. Results: In the total patient group, patients with positive pre-MRD had a higher 4-year cumulative incidence of relapse (CIR) than that in patients with negative pre-MRD (26.1% vs. 12.1%, P = 0.009); however, the cumulative incidence of non-relapse mortality (NRM) (7.4% vs. 15.9%, P = 0.148), probability of leukemia-free survival (LFS) (66.3% vs. 71.4%, P = 0.480), and overall survival (OS) (68.8% vs. 76.5%, P = 0.322) were comparable. In the MSDT group, patients with positive pre-MRD had increased 4-year CIR (56.4% vs. 13.8%, P < 0.001) and decreased 4-year LFS (35.9% vs. 71.0%, P = 0.024) and OS (35.9% vs. 77.6%, P = 0.011) compared with those with negative pre-MRD. In haplo-SCT settings, the 4-year CIR (14.8% vs. 10.7%, P = 0.297), NRM (7.3% vs. 16.3%, P = 0.187) and the 4-year probability of OS (77.7% vs. 72.3%, P = 0.804) and LFS (80.5% vs. 75.7%, P = 0.660) were comparable between pre-MRD positive and negative groups. In subgroup patients with positive pre-MRD, haplo-SCT had a lower 4-year CIR (14.8% vs. 56.4%, P = 0.021) and a higher 4-year LFS (77.7% vs. 35.9%, P = 0.036) and OS (80.5% vs. 35.9%, P = 0.027) than those of MSDT. Multivariate analysis showed that haplo-SCT was associated with lower CIR (HR, 0.288; P = 0.031), superior LFS (HR, 0.283; P = 0.019) and OS (HR, 0.252; P = 0.013) in cases with a positive pre-MRD subgroup. Li et al. Pre-MRD on Ph + ALL Outcomes Conclusions: Our results indicate that the effects of positive pre-MRD on the outcomes of patients with Ph-positive ALL are different according to transplant modality. For Ph-positive cases with positive pre-MRD, haplo-SCT might have strong graft-vs.-leukemia (GVL) effects.

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Section: Discussionmentioning

confidence: 99%

Different Effects of Pre-transplantation Measurable Residual Disease on Outcomes According to Transplant Modality in Patients With Philadelphia Chromosome Positive ALL

Fan

et al. 2020

Front. Oncol.

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“…In acute lymphocytic leukemia (ALL), the necessity of TBI has also been challenged in comparison to a BU IV-based chemotherapy. The MD Anderson group demonstrated a similar outcome to a TBI-based myeloablative (MA) alloHCT for ALL, albeit with different relapse and toxicity profiles [75,76]. However a recent randomized trial in pediatric patients with ALL demonstrated that TBI plus etoposide conditioning resulted in an improved overall survival (OS) and lower relapse risk [77].…”

Section: Methods To Minimize the Dose Of Tbimentioning

confidence: 99%

Total Body Irradiation for Hematopoietic Stem Cell Transplantation: What Can We Agree on?

Sabloff

Tisseverasinghe²,

Babadağli

et al. 2021

Current Oncology

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Total body irradiation (TBI), used as part of the conditioning regimen prior to allogeneic and autologous hematopoietic cell transplantation, is the delivery of a relatively homogeneous dose of radiation to the entire body. TBI has a dual role, being cytotoxic and immunosuppressive. This allows it to eliminate disease and create “space” in the marrow while also impairing the immune system from rejecting the foreign donor cells being transplanted. Advantages that TBI may have over chemotherapy alone are that it may achieve greater tumour cytotoxicity and better tissue penetration than chemotherapy as its delivery is independent of vascular supply and physiologic barriers such as renal and hepatic function. Therefore, the so-called “sanctuary” sites such as the central nervous system (CNS), testes, and orbits or other sites with limited blood supply are not off-limits to radiation. Nevertheless, TBI is hampered by challenging logistics of administration, coordination between hematology and radiation oncology departments, increased rates of acute treatment-related morbidity and mortality along with late toxicity to other tissues. Newer technologies and a better understanding of the biology and physics of TBI has allowed the field to develop novel delivery systems which may help to deliver radiation more safely while maintaining its efficacy. However, continued research and collaboration are needed to determine the best approaches for the use of TBI in the future.

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“…The transplantation of hematopoietic stem and progenitor cells (HSPC) from human bone marrow (BM), adult mobilized peripheral blood (MPB) or umbilical cord blood (CB) has for more than 50 years been employed as an effective treatment for a variety of blood disorders and malignancies ( Juric et al, 2016 ; Takami, 2018 ; DeFilipp et al, 2019 ). An important approach to assess their potency and predict the likelihood of robust engraftment is to determine the number and quality of lineage-specific progenitor cells and multipotent stem cells among the cells to be transplanted.…”

Section: Automated Classification and Quantitation Of Colonies Of Blomentioning

confidence: 99%

Automation, Monitoring, and Standardization of Cell Product Manufacturing

Doulgkeroglou

Nubila

Nießing

et al. 2020

Front. Bioeng. Biotechnol.

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Although regenerative medicine products are at the forefront of scientific research, technological innovation, and clinical translation, their reproducibility and large-scale production are compromised by automation, monitoring, and standardization issues. To overcome these limitations, new technologies at software (e.g., algorithms and artificial intelligence models, combined with imaging software and machine learning techniques) and hardware (e.g., automated liquid handling, automated cell expansion bioreactor systems, automated colony-forming unit counting and characterization units, and scalable cell culture plates) level are under intense investigation. Automation, monitoring and standardization should be considered at the early stages of the developmental cycle of cell products to deliver more robust and effective therapies and treatment plans to the bedside, reducing healthcare expenditure and improving services and patient care.

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Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy

Cited by 80 publications

References 121 publications

Different Effects of Pre-transplantation Measurable Residual Disease on Outcomes According to Transplant Modality in Patients With Philadelphia Chromosome Positive ALL

Different Effects of Pre-transplantation Measurable Residual Disease on Outcomes According to Transplant Modality in Patients With Philadelphia Chromosome Positive ALL

Total Body Irradiation for Hematopoietic Stem Cell Transplantation: What Can We Agree on?

Automation, Monitoring, and Standardization of Cell Product Manufacturing

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