Pretransplant Consolidation Is Not Beneficial for Adults with ALL Undergoing Myeloablative Allogeneic Transplantation

Bejanyan, Nelli; Zhang, Mei Jie; Wang, Hai Lin; Lazaryan, Aleksandr; Lima, Marcos J.G. de; Marks, David I.; Sandmaier, Brenda M.; Bachanová, Veronika; Rowe, Jacob M.; Tallman, Martin S.; Kebriaei, Partow; Kharfan‐Dabaja, Mohamed A.; Gale, Robert Peter; Lazarus, Hillard M.; Üstün, Celalettin; Copelan, Edward A.; Hamilton, Betty K.; Schiller, Gary J.; Hashmi, Shahrukh K.; Seftel, Matthew D.; Kanakry, Christopher G.; Olsson, Richard F.; Martino, Rodrigo; Saber, Wael; Khoury, H. Jean; Weisdorf, Daniel J.

doi:10.1016/j.bbmt.2017.12.784

Cited by 7 publications

(3 citation statements)

References 42 publications

(38 reference statements)

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“…A large analysis of Center for International Blood and Marrow Transplant Research data on 524 ALL patients demonstrated that chemotherapy provided no Values are n (%). apparent advantage for CR1 patients with an immediately available donor considered for a prompt myeloablative allo-HSCT [28]. Moreover, additional intensive chemotherapy might not always reduce the leukemia burden because of enhanced resilience of leukemia cells that survive the multiagent regimens [29].…”

Section: Discussionmentioning

confidence: 99%

Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease

Zhang

Wang

et al. 2019

Biology of Blood and Marrow Transplantation

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The optimal conditioning regimen of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients with minimal residual disease (MRD) remains controversial. We studied the results in 98 high-risk acute leukemia patients transplanted with idarubicin (IDA)-intensified conditioning regimens between 2012 January and 2017 January. Among these patients, 31 (31.6%) had more than 5% marrow blasts at time of transplantation and 67 patients were in morphologic remission: MRD negative status at time of conditioning was achieved in 39 patients (39.8%), whereas 28 (28.6%) remained carriers of any other positive MRD level in the bone marrow. Three-year relapse estimates of patients with MRD-positive remission was 22.0%, which was remarkably lower than patients with active disease (45.4%, P = .027) but approximate to that of patients in MRD-negative remission (15.5%, P = .522). There were no significant differences in terms of 3-year estimated overall survival (OS) and disease-free survival (DFS) between MRD-positive remission and MRD-negative remission groups (71.4% versus 79.1% [P = .562] and 67.9% versus 76.9% [P = .634], respectively). Moreover, the estimated rates of 3-year OS and DFS of patients in MRD-positive remission were significantly better than those in patients with active disease (71.4% versus 41.9% [P = .033] and 67.9% versus 38.7% [P = .037], respectively). These data indicate that IDA-intensified conditioning allo-HSCT could overcome the negative prognostic impact of MRD.

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Section: Discussionmentioning

confidence: 99%

Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease

Zhang

Wang

et al. 2019

Biology of Blood and Marrow Transplantation

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“…These data will help determine which therapies should be applied as a bridge to transplantation and which therapies in selected patients may supplant allo-HCT. Pre-HCT bridging therapy, including additional pre-HCT consolidation [119], might increase toxicities such as GVHD and veno-occlusive disease, when these therapies are used sequentially. Targeted and immune therapies may also have an expanding role for patients with MRD after allo-HCT.…”

Section: Areas Of Needed Researchmentioning

confidence: 99%

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

Advani

Bachanová

et al. 2019

Biology of Blood and Marrow Transplantation

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The role of hematopoietic cell transplantation (HCT) in adults with acute lymphoblastic leukemia (ALL) is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of ALL experts developed consensus on the treatment recommendations based on the evidence. Allogeneic HCT offers a survival benefit in selected patients with ALL, and this review summarizes the standard indications as well as the areas of controversy. There is now greater experience with pediatric-inspired chemotherapy regimens that has transformed upfront therapy for adult ALL, resulting in higher remission rates and overall survival. This in turn has increased the equipoise around decision making for ALL in first complete remission (CR1) when there is no measurable residual disease (MRD) at the end of induction and/or consolidation. Randomized studies are needed for adults with ALL to compare allogeneic HCT in CR1 with pediatric-inspired chemotherapy alone. Indications for transplantation in the evolving landscape of MRD assessments and novel targeted and immune therapeutics remain important areas of investigation.

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“…Even if HSCT is curative for an ALL patient in CR1, the benefits of consolidation chemotherapy do not appear to add any significant benefit for patients with available donors who undergo a myeloablative HSCT, as proven by the study coordinated by Weisforf et al [89]. In 524 adult patients with ALL in CR1 who received at least two, one, or no cycles of consolidation before myeloablative HSCT from 2008 to 2012, those receiving at least two, one, or no cycles of consolidation had an adjusted 3-year cumulative incidence of relapse of 20%, 27%, and 22%.…”

Section: Allogeneic Stem Cell Transplantation For Allmentioning

confidence: 99%

Approach to the Adult Acute Lymphoblastic Leukemia Patient

Sas

Moisoiu

Teodorescu

et al. 2019

JCM

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During recent decades, understanding of the molecular mechanisms of acute lymphoblastic leukemia (ALL) has improved considerably, resulting in better risk stratification of patients and increased survival rates. Age, white blood cell count (WBC), and specific genetic abnormalities are the most important factors that define risk groups for ALL. State-of-the-art diagnosis of ALL requires cytological and cytogenetical analyses, as well as flow cytometry and high-throughput sequencing assays. An important aspect in the diagnostic characterization of patients with ALL is the identification of the Philadelphia (Ph) chromosome, which warrants the addition of tyrosine kinase inhibitors (TKI) to the chemotherapy backbone. Data that support the benefit of hematopoietic stem cell transplantation (HSCT) in high risk patient subsets or in late relapse patients are still questioned and have yet to be determined conclusive. This article presents the newly published data in ALL workup and treatment, putting it into perspective for the attending physician in hematology and oncology.

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Pretransplant Consolidation Is Not Beneficial for Adults with ALL Undergoing Myeloablative Allogeneic Transplantation

Cited by 7 publications

References 42 publications

Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease

Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease

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

Approach to the Adult Acute Lymphoblastic Leukemia Patient

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