Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplantation

Bitan, Menachem; Ahn, Kwang Woo; Millard, Heather R.; Pulsipher, Michael A.; Abdel‐Azim, Hisham; Auletta, Jeffery J.; Brown, Valerie I.; Chan, Ka Wah; Díaz, Miguel Ángel; Dietz, Andrew C.; Vincent, Marta Gonzalez; Guilcher, Gregory M.T.; Hale, Gregory A.; Hayashi, Robert J.; Keating, Amy K.; Mehta, Parinda A.; Myers, Kasiani C.; Page, Kristin; Prestidge, Tim; Shah, Nirali N.; Smith, Angela R.; Woolfrey, Ann E.; Thiel, Elizabeth; Davies, Stella M.; Eapen, Mary

doi:10.1016/j.bbmt.2017.05.011

Cited by 14 publications

(12 citation statements)

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“…The spectrum of conditioning regimens used in the present analysis is wide, and in the absence of an association with relapse or survival, we conclude that the transplantation conditioning regimen for second HCT should be tailored for the individual patient considering his or her HCT Comorbidity Index, overall fitness for second HCT, and perhaps their response to reinduction chemotherapy (ie, remission and MRD status) before transplantation. We observed higher LFS in patients with a history of chronic GVHD after first HCT, consistent with other reports [18]; however, in another study from our group that focused on predictors for late mortality, chronic GVHD was a significant predictor of death [32].…”

Section: Discussionsupporting

confidence: 92%

Outcomes after Second Hematopoietic Cell Transplantation in Children and Young Adults with Relapsed Acute Leukemia

Lund

Ahn

Tecca

et al. 2019

Biology of Blood and Marrow Transplantation

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Children with acute leukemia who relapse after hematopoietic cell transplantation (HCT) have few therapeutic options. We studied 251 children and young adults with acute myelogenous or lymphoblastic leukemia who underwent a second HCT for relapse after their first HCT. The median age at second HCT was 11 years, and the median interval between first and second HCT was 17 months. Most of the patients (n = 187; 75%) were in remission, received a myeloablative conditioning regimen (n = 157; 63%), and underwent unrelated donor HCT (n = 230; 92%). The 2-year probability of leukemia-free survival (LFS) was 33% after transplantation in patients in remission, compared with 19% after transplantation in patients not in remission (P = .02). The corresponding 8-year probabilities were 24% and 10% (P = .003). A higher rate of relapse contributed to the difference in LFS. The 2-year probability of relapse after transplantation was 42% in patients in remission and 56% in those in relapse (P = .05). The corresponding 8-year probabilities were 49% and 64% (P = .04). These data extend the findings of others showing that patients with a low disease burden are more likely to benefit from a second transplantation. Late relapse led to a 10% decrement in LFS beyond the second year after second HCT. This differs from first HCT, in which most relapses occur within 2 years after HCT.

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Section: Discussionsupporting

confidence: 92%

Outcomes after Second Hematopoietic Cell Transplantation in Children and Young Adults with Relapsed Acute Leukemia

Lund

Ahn

Tecca

et al. 2019

Biology of Blood and Marrow Transplantation

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“…Others have shown the adverse effect of chronic GVHD on survival in children and adolescents with AML and ALL with sustained remission for at least 1 year after related or unrelated donor transplantation. 18 …”

Section: Discussionmentioning

confidence: 99%

Bone Marrow versus Peripheral Blood from Unrelated Donors for Children and Adolescents with Acute Leukemia

Keesler

Martin

Bonfim

et al. 2018

Biology of Blood and Marrow Transplantation

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Graft-versus-host disease (GVHD) rates are higher after unrelated donor transplantation; thus, we examined whether there would be differences in transplant outcomes by graft type in children and adolescents with acute leukemia. The primary endpoint was overall survival. We studied 872 patients <18 years old who were transplanted with bone marrow (n = 650) or peripheral blood (n = 222) from unrelated donors. The characteristics of the 2 groups were comparable, except recipients of bone marrow were younger than recipients of peripheral blood (median age, 10 versus 12 years). Grades 2 to 4 (hazard ratio [HR], 1.48; P < .001) and grades 3 and 4 acute (HR, 1.69; P < .001) and chronic GVHD (HR, 1.92; P < .001) were higher with transplantation of peripheral blood than with bone marrow. Although relapse risks were lower after peripheral blood transplants (HR, 0.76; P = .05), transplant-related mortality (HR, 1.91; P = .003) and overall mortality (HR, 1.34; P = .032) were higher than with bone marrow transplants. The 8-year probability of overall survival after transplantation of bone marrow was 47% compared with 42% after peripheral blood. The 8-year probability of leukemia-free survival was 40% after transplantation of bone marrow and peripheral blood. Lower relapse after transplantation of peripheral blood negated the survival advantage after transplantation of bone marrow. The observed higher acute and chronic GVHD seen with peripheral blood suggest cautious use of this graft in children and adolescents with acute leukemia.

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“…Disease status remains a strong independent factor in relapse, toxicity and death after HSCT. In all recent studies, more advanced disease is still correlated with death for both adults [17,18] and children [19] in spite of improvements in salvage therapies [20]; it is the same for the minimal residual disease (MRD) which is a strong prognostic factor before HSCT [21,22]. Refractory AML has a very bad prognosis despite efforts to develop new strategies such as sequential regimen, except in patients with low medullar blast burden in primary refractory AML [23].…”

Section: Discussionmentioning

confidence: 99%

Improved Outcome in Young Children Compared to Adolescents and Adults After Allogeneic Hematopoietic Stem Cell Transplant for Acute Myeloid Leukemia: a Retrospective Study From Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) (SFGM-TC)

Pochon

Detrait

Dalle

et al. 2021

Preprint

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Background: There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents and young adults (AYAs) after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, AYAs and adults after a first allogeneic HSCT for AML. Methods: In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation’s time: children (<15 years, n=564), AYAs (15-25 years, n=647) and adults (26-40 years; n= 1434). Results: With a median follow-up of 4.37 years (min-max 0.18 – 14.73 years), the probability of 2 year-overall survival (OS) was 71.4% in children, 61.1% in AYAs and 62.9% in adults (p=0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for AYAs and 29.4% for adults - p=0.0254, and 7.0% for children, 10.6% for AYAs and 14.2% for adults, p<0.0001; respectively). Whilst there was no difference between the 3 groups for grade I to IV acute GVHD CI at 3 months, the chronic GVHD CI at 2 years was higher in AYAs and adults (31.4% and 36.4%, respectively) in comparison to the children (17.5%) (p<0.0001). In multivariable analysis, factors associated with death were AML cytogenetics (HR1.73 [1.29-2.32] for intermediate risk 1, HR 1.50 [1.13-2.01] for intermediate risk 2, HR 2.22 [1.70-2.89] for high cytogenetics risk compared to low risk), use of TBI ≥ 8 Grays (HR 1.33 [1.09-1.61]), disease status at transplant (HR 1.40 [1.10-1.78] for second Complete Remission (CR), HR 2.26 [1.02-4.98] for third CR and HR 3.07 [2.44-3.85] for active disease, compared to first CR), graft source (HR 1.26 [1.05-1.50] for Peripheral Blood Stem Cells compared to Bone Marrow) and donor age (HR 1.01 (1-1.02] by increase of one year). Conclusion: Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that AYAs AML patients should be treated with chemotherapy-based MAC regimen and bone marrow as stem cells source.

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Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplantation

Cited by 14 publications

References 20 publications

Outcomes after Second Hematopoietic Cell Transplantation in Children and Young Adults with Relapsed Acute Leukemia

Outcomes after Second Hematopoietic Cell Transplantation in Children and Young Adults with Relapsed Acute Leukemia

Bone Marrow versus Peripheral Blood from Unrelated Donors for Children and Adolescents with Acute Leukemia

Improved Outcome in Young Children Compared to Adolescents and Adults After Allogeneic Hematopoietic Stem Cell Transplant for Acute Myeloid Leukemia: a Retrospective Study From Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) (SFGM-TC)

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