Adult cord blood transplant results in comparable overall survival and improved GRFS vs matched related transplant

Sharma, Prashant; Purev, Enkhtsetseg; Haverkos, Bradley M.; Pollyea, Daniel A.; Cherry, Evan; Kamdar, Manali; Mark, Tomer M.; Forsberg, Peter; Sherbenou, Daniel W.; Hammes, Andrew; Rabinovitch, Rachel; Smith, Clayton A.; Gutman, Jonathan A.

doi:10.1182/bloodadvances.2020001554

Cited by 42 publications

(38 citation statements)

References 35 publications

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“…Double unit cord blood transplantation (dCBT) can be efficacious in adults with high-risk hematologic malignancies with comparable progression-free survival (PFS) to that of adult donor transplantation in many series. [1][2][3][4] However, dCBT after high-intensity or nonmyeloablative (NMA) conditioning has limitations. High-intensity regimens are toxic and have been associated with excessive transplant-related mortality (TRM).…”

Section: Introductionmentioning

confidence: 99%

High progression-free survival after intermediate intensity double unit cord blood transplantation in adults

et al. 2020

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Cord blood transplantation (CBT) after high intensity or nonmyeloablative conditioning has limitations. We investigated cyclosporine-A/mycophenolate mofetil–based intermediate intensity (cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, thiotepa 10 mg/kg, total body irradiation 400 cGy) unmanipulated double-unit CBT (dCBT) with prioritization of unit quality and CD34+ cell dose in graft selection. Ninety adults (median age, 47 years [range, 21-63]; median hematopoietic cell transplantation comorbidity index, 2 [range, 0-8]; 61 [68%] acute leukemia) received double-unit grafts (median CD34+ cell dose, 1.3 × 105/kg per unit [range, 0.2-8.3]; median donor-recipient human leukocyte antigen (HLA) match, 5/8 [range 3-7/8]). The cumulative incidences of sustained CB engraftment, day 180 grade III-IV acute, and 3-year chronic graft-versus-host disease were 99%, 24%, and 7%, respectively. Three-year transplant-related mortality (TRM) and relapse incidences were 15% and 9%, respectively. Three-year overall survival (OS) is 82%, and progression-free survival (PFS) is 76%. Younger age and higher engrafting unit CD34+ cell dose both improved TRM and OS, although neither impacted PFS. Engrafting unit-recipient HLA match was not associated with any outcome with a 3-year PFS of 79% in 39 patients engrafting with 3-4/8 HLA-matched units. In 52 remission acute leukemia patients, there was no association between minimal residual disease (MRD) and 3-year PFS: MRD negative of 88% vs MRD positive of 77% (P = .375). Intermediate intensity dCBT is associated with high PFS. Use of highly HLA mismatched and unmanipulated grafts permits wide application of this therapy, and the low relapse rates support robust graft-versus-leukemia effects even in patients with MRD.

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Section: Introductionmentioning

confidence: 99%

High progression-free survival after intermediate intensity double unit cord blood transplantation in adults

et al. 2020

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“…Similarly, a comparison of unrelated HLA-mismatched UCBT to matched unrelated adult donors transplants in paediatric patients demonstrated recipients of the UCBT experienced delayed engraftment but less acute and chronic GVHD with a similar relapse rate, OS and LFS (Rocha et al, 2001). Similar OS and significantly improved cGvHD and relapse-free survival were reported for adult patients with different malignant conditions after UCBT compared with matched sibling PBSC in a single-centre study in Colorado (Sharma et al, 2020).…”

Section: Use Of Ucbmentioning

confidence: 65%

BSHI guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

Little

Akbarzad‐Yousefi

Anand

et al. 2021

Int J Immunogenetics

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“…GVHD frequency and intensity can be decreased when using T cells obtained from UCB, as these have reduced reactivity due to lower activation of the NF-κB pathway, resulting in decreased production of several pro-inflammatory cytokines ( 56 , 57 ). In the context of hematopoietic stem cell transplantation (SCT) for treatment of hematological malignancies, UCB transplantation has indeed shown better results than matched unrelated donors and similar results as compared to matched related donor transplantation with regard to GVHD incidence, late complications and overall survival ( 58 – 60 ). CAR T cells derived from UCB have already been used, showing the feasibility of the approach, as well as efficacy, as UCB-derived CAR T cells were able to recognize and kill target cells ( 61 ).…”

Section: Allogeneic Car T Cellsmentioning

confidence: 99%

Allogeneic CAR T Cells: An Alternative to Overcome Challenges of CAR T Cell Therapy in Glioblastoma

2021

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Chimeric antigen receptor (CAR) T cell therapy has emerged as one of the major breakthroughs in cancer immunotherapy in the last decade. Outstanding results in hematological malignancies and encouraging pre-clinical anti-tumor activity against a wide range of solid tumors have made CAR T cells one of the most promising fields for cancer therapies. CAR T cell therapy is currently being investigated in solid tumors including glioblastoma (GBM), a tumor for which survival has only modestly improved over the past decades. CAR T cells targeting EGFRvIII, Her2, or IL-13Rα2 have been tested in GBM, but the first clinical trials have shown modest results, potentially due to GBM heterogeneity and to the presence of an immunosuppressive microenvironment. Until now, the use of autologous T cells to manufacture CAR products has been the norm, but this approach has several disadvantages regarding production time, cost, manufacturing delay and dependence on functional fitness of patient T cells, often reduced by the disease or previous therapies. Universal “off-the-shelf,” or allogeneic, CAR T cells is an alternative that can potentially overcome these issues, and allow for multiple modifications and CAR combinations to target multiple tumor antigens and avoid tumor escape. Advances in genome editing tools, especially via CRISPR/Cas9, might allow overcoming the two main limitations of allogeneic CAR T cells product, i.e., graft-vs.-host disease and host allorejection. Here, we will discuss how allogeneic CAR T cells could allow for multivalent approaches and alteration of the tumor microenvironment, potentially allowing the development of next generation therapies for the treatment of patients with GBM.

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Adult cord blood transplant results in comparable overall survival and improved GRFS vs matched related transplant

Cited by 42 publications

References 35 publications

High progression-free survival after intermediate intensity double unit cord blood transplantation in adults

High progression-free survival after intermediate intensity double unit cord blood transplantation in adults

BSHI guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

Allogeneic CAR T Cells: An Alternative to Overcome Challenges of CAR T Cell Therapy in Glioblastoma

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