Outcomes with CD34-Selected Stem Cell Boost for Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Shahzad, Moazzam; Siddiqui, Raheel S; Anwar, Iqra; Chaudhary, Sibgha Gull; Ali, Tayyaba; Naseem, Masooma; Ahmed, Tehniat Faraz; Ahmed, Zahoor; Khurana, Sharad; Ahmed, Nausheen; Balusu, Ramesh; Singh, Anurag K.; Hematti, Peiman; Callander, Natalie S.; Abhyankar, Sunil; McGuirk, Joseph P.; Mushtaq, Muhammad Umair

doi:10.1016/j.jtct.2021.07.012

Cited by 29 publications

(34 citation statements)

References 32 publications

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“…Several studies demonstrated that no deficit was found in the cells’ capacity to repopulate the marrow when stored CD34+ cells from donors whose recipients developed PGF were xenografted to mice ( 30 ). Moreover, donor-derived CD34+ cells boost is an emerging therapeutic option with promising response rates in patients with sPGF, as presented in this report and others ( 31 – 33 ). Taken together with these findings, these data suggests that the deficits in “seed” are acquired after transplantation.…”

Section: Discussionsupporting

confidence: 66%

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

et al. 2022

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Secondary poor graft function (sPGF) increases the risk of life-threatening complications after hematopoietic stem cell transplantation (HSCT). The incidence, clinical outcomes, and risk factors of sPGF have not been elucidated in haploidentical (haplo-) HSCT for acquired aplastic anemia (AA) patients. We retrospectively reviewed 423 consecutive AA patients who underwent haplo-HSCT between January 2006 and December 2020 and report a 3-year cumulative incidence of 4.62% (95% confidence interval [CI]: 3.92%-10.23%) of sPGF. While no primary PGF occurred. The median time to sPGF was 121 days (range 30-626 days) after transplantation. To clarify the risk factors for sPGF, 17 sPGF cases and 382 without PGF were further analyzed. Compared to patients without PGF, the 2-year overall survival was significantly poorer for sPGF patients (67.7% vs 90.8%, p =.002). Twelve sPGF patients were alive until the last follow-up, and 7 achieved transfusion independency. The multivariable analyses revealed that later neutrophil engraftment (OR 2.819, p=.049) and a history of refractory cytomegalovirus viremia (OR=7.038, p=.002) post-transplantation were associated with sPGF. There was weak evidence that a history of grade 3-4 acute graft-versus-host disease increased the risk of sPGF (p=.063). We advocated better post-transplantation strategies to balance the risk of immunosuppression and viral reactivation for haplo-HSCT in AA patients.

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Section: Discussionsupporting

confidence: 66%

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

et al. 2022

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“…In contrast to Miller’s group, Shapiro and colleagues did not demonstrate substantial GVHD in their study, which they concluded was due to administration of NK cells with IL-2 rather than IL-15 ( 2 ). In contrast, the most notable adverse event identified in Shapiro et al ( 2 ) was pancytopenia, which required a CD34 + stem cell boost ( 15 ) in 2 patients. This prolonged aplasia has also been observed in allogeneic chimeric antigen receptor T cell (CAR-T) recipients.…”

Section: An Nk Cell Eramentioning

confidence: 93%

Harnessing allogeneic NK cells: improving outcomes with tailored donor lymphocyte infusion

McCurdy¹

2022

Journal of Clinical Investigation

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Since researchers first began to uncover the mechanisms underlying allogeneic transplantation, the focus has been on T cells. T cells are a major instigator of graft-versus-host disease (GVHD). The clear association between GVHD occurrence and subsequent reduction in relapse supported concentrating on T cells as the masterminds behind graft-versus-tumor (GVT) effects. Recently, an alternative mediator of GVT has taken center stage: natural killer (NK) cells. Part of the appeal of NK cells is their potential to provide antitumor immunity without GVHD. Donor lymphocyte infusion has been the predominant treatment of relapse after allogeneic transplant, but the mix of lymphocytes includes CD8 + T cells and, consequently, a substantial risk for GVHD. In this issue of the JCI , Shapiro and colleagues developed an adoptive NK cell transfer platform to treat relapse after haploidentical allogeneic transplant. The study demonstrated safety, sought to determine resistance mechanisms, and provided avenues for future research.

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“…The median time from allo-SCT to SCB was 138 days (range 113–450) and the median SCB dose 3.45 × 10 6 CD34 cell/kg (range 3.1–4.9). Complete response and overall response rates were 72% (95% CI, 63–79%) and 80% (95% CI, 74–85%), respectively [ 17 ]. Regarding CD3 T cells, a lower number (median 1.27 × 10 3 cells/kg) was reported by Mohty et al who did not find any cases of GVHD.…”

Section: Management Of Post-transplant Thrombocytopeniamentioning

confidence: 99%

Thrombocytopenia and Therapeutic Strategies after Allogeneic Hematopoietic Stem Cell Transplantation

Bento

Canaro

Bastida

et al. 2022

JCM

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Thrombocytopenia following allogeneic hematopoietic stem cell transplantation is a usual complication and can lead to high morbidity and mortality. New strategies, such as the use of another graft versus host-disease prophylaxis, alternative donors, and management of infections, have improved the survival of these patients. The mechanisms are unknown; therefore, the identification of new strategies to manage this potentially serious problem is needed. Thrombopoietin receptor agonists are currently available to stimulate platelet production. Some small retrospective studies have reported their potential efficacy in an allogeneic stem cell transplant setting, confirming good tolerability. Recent studies with higher numbers of patients also support their safety and efficacy in this setting, hence establishing the use of these drugs as a promising strategy for this post-transplant complication. However, prospective trials are needed to confirm these results.

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Outcomes with CD34-Selected Stem Cell Boost for Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Cited by 29 publications

References 32 publications

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

Harnessing allogeneic NK cells: improving outcomes with tailored donor lymphocyte infusion

Thrombocytopenia and Therapeutic Strategies after Allogeneic Hematopoietic Stem Cell Transplantation

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