Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults

Khaled, Samer K.; Thomas, Sandra H.; Forman, Stephen J.

doi:10.1097/cco.0b013e32834f5c41

Cited by 28 publications

(16 citation statements)

References 73 publications

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“…The initial clinical indications for use of expanded HSPCs will be the malignant and non‐malignant blood and immune diseases that are currently being treated by HSPC transplants but are limited by availability of donors and low cell numbers (current indications are reviewed in 66–72). Approximately 60% of allogeneic HSPC transplants are performed for the treatment of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome and myeloproliferative disorders.…”

Section: Forward Looking To Hspc Derived Cell Therapiesmentioning

confidence: 99%

Blood stem cell products: Toward sustainable benchmarks for clinical translation

2013

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Robust ex vivo expansion of umbilical cord blood (UCB) derived hematopoietic stem and progenitor cells (HSPCs) should enable the widespread use of UCB as a source of cells to treat hematologic and immune diseases. Novel approaches for HSPC expansion have recently been developed, setting the stage for the production of blood stem cell derived products that fulfill our current best known criteria of clinical relevance. Translating these technologies into clinical use requires bioengineering strategies to overcome challenges of scale-up, reproducibility, and product quality assurance. Clinical-scale implementation should also define criteria and targets for cost-effective cell manufacturing. As production strategies become more effective, new opportunities in the therapeutic use of ex vivo expanded hematopoietic cell products will emerge. Herein we examine key technological milestones that need to be met in order to move ex vivo expanded HSPC therapies from the bench-top to the bedside in a robust and reliable manner.

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Section: Forward Looking To Hspc Derived Cell Therapiesmentioning

confidence: 99%

Blood stem cell products: Toward sustainable benchmarks for clinical translation

2013

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“…Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment option for patients with acute leukemia(1, 2). Despite recent advances in HLA matching, conditioning regimens, and supportive care, post-HCT mortality and morbidity risks are still high(3).…”

Section: Introductionmentioning

confidence: 99%

Relative Telomere Length before Hematopoietic Cell Transplantation and Outcome after Unrelated Donor Hematopoietic Cell Transplantation for Acute Leukemia

Wang

Dagnall

et al. 2017

Biology of Blood and Marrow Transplantation

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Telomeres are tandem nucleotide repeats and a protein complex located at the end of the chromosomes maintaining genomic stability. Their potential as a predictive biomarker for outcomes after allogeneic hematopoietic cell transplant (HCT) in hematologic malignancies is still unclear. From the Center for International Blood and Marrow Transplant Research (CIBMTR), we randomly selected 536 acute leukemia (AL) patients from those who underwent myeloablative 8/8 HLA-matched unrelated donor HCT between 2005 and 2012, and who had an available pre-HCT blood sample in the repository. RTL was measured by real time qPCR. We used Kaplan-Meier and competing risk estimators to calculate survival probability and cumulative incidence, respectively across patient RTL tertiles. Cox proportional hazard regression was used for adjusted analyses. The study included 396 AML and 140 ALL patients. Median age at HCT=41 years, range 0.5–66 years, and median follow-up for survivors=5.1 years (range= 0.4–8.3). Significant inverse correlations between age and RTL were observed in patients with AML (r=−0.44, p<0.0001), and ALL (r=−0.48 p<0.0001). Patients with ALL had longer RTL than those with AML (mean T/S= 0.48 vs. 0.43, respectively); the difference was not statistically significant after adjusting for patient age (p=0.96). Pre-HCT RTL in AL patients was not statistically significantly associated with overall survival (HR for longest RTL compared with shortest=0.91, 95% CI=0.65–1.28), disease free survival (HR=0.90, 95% CI=0.64–1.25), transplant related mortality (HR=0.97, 95% CI=0.60–1.59), incidence of relapse (HR=0.89, 95% CI=0.56–1.40), neutrophil engraftment (HR=1.06, 95% CI=0.85–1.32), or acute (HR=1.11, 95% CI=0.81–1.53 for grade II–IV, HR=0.92, 95% CI=0.54–1.59 for grade III–IV) and chronic graft-versus-host disease (HR=1.10, 95% CI=0.81–1.50). In this study, recipient pre-HCT RTL had no prognostic role in post-transplant outcomes in AL patients.

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“…Furthermore, with the development of haploidentical transplantations, there are increased donor options that improve the chances of moving quickly to transplantation without a reinduction attempt in patients with a low disease burden (ie, detectable by MRD or morphologically as Ͻ 10% blasts). 35 The United States lags far behind Europe in performing appropriate molecular disease assessments that would enable determination of the depth of the remission and the likelihood of relapse in patients who achieve remission. Many practitioners still rely on morphology and cytogenetics, including FISH, to document remission and follow blood counts and BM results over time.…”

Section: Transplantation Regimens In the Management Of Relapsed Leukemiamentioning

confidence: 99%

The myth of the second remission of acute leukemia in the adult

Forman

Rowe

2013

Blood

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202

152

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Although the majority of adult patients with both acute lymphoblastic leukemia and acute myelogenous leukemia achieve remission with upfront chemotherapy, many patients still suffer relapse. Often, the strategy is proposed of treating patients with relapsed leukemia into a second remission (CR2) and then proceeding to allogeneic transplantation as the definitive curative approach. However, the longterm outcomes of such a strategy are poor: the 5-year overall survival from first relapse for patients with acute leukemia is only approximately 10%. This Perspective highlights the fact that most patients do not achieve CR2 and therefore never really have an opportunity for a potential curative therapy. Although patients who undergo transplantation after relapse may be cured, those who do not achieve CR2 are rarely candidates for transplantation; therefore, the overall outcome for patients who relapse is dismal. There is therefore an urgent need not only for more effective upfront therapy to prevent relapse, but also for the development of therapies that can serve as effective bridging treatments between relapse and transplantation. We suggest that more optimal use of minimal residual disease detection during first remission may also improve the chances for successful transplantation therapy via earlier reinduction therapy, allowing transplantation before overt relapse. (Blood. 2013;121(7): 1077-1082) IntroductionWhen adults are diagnosed with acute leukemia, it is very common for the physician to discuss with them the potential role, timing, risks, and impact of hematopoietic cell transplantation in the management of their disease. This often leads to recommending early transplantation for patients with high-risk disease in first remission (CR1) and delaying transplantation for those with a lower risk of relapse until there is evidence of recurrent disease. The assumption is that after relapse or progression, patients will undergo transplantation after successful reinduction therapy to achieve CR2.In general, for patients with acute myeloid leukemia (AML), allogeneic related or unrelated transplantation is currently pursued for those with intermediate-or high-risk disease, specifically those with FLT3 mutations, intermediate-or high-risk cytogenetics, complex cytogenetics, monosomy karyotypes, or who did not achieve remission with the initial induction therapy. For those patients who have favorable-risk AML, transplantations have not been shown to be beneficial and are not generally performed in CR1. 1 These include normal cytogenetics if the leukemia cells display molecular features such as NPM1 mutations because these patients often have comparable outcomes with standard chemotherapy. This also applies to patients with good-risk cytogenetics such as inv(16) or t(8;21) for whom, in the absence of other concomitant risk factors such as genes associated with a stem cell phenotype, transplantation is generally delayed in the hopes that they will be cured with repeated courses of upfront cytarabinebased consolidation th...

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Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults

Cited by 28 publications

References 73 publications

Blood stem cell products: Toward sustainable benchmarks for clinical translation

Blood stem cell products: Toward sustainable benchmarks for clinical translation

Relative Telomere Length before Hematopoietic Cell Transplantation and Outcome after Unrelated Donor Hematopoietic Cell Transplantation for Acute Leukemia

The myth of the second remission of acute leukemia in the adult

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