Allogeneic stem cell transplantation (allo-SCT) for de novo Ph+ AML: a study from the French Society of Bone Marrow Transplantation and Cell Therapy

Chantepie, Sylvain; Michallet, Mauricette; Blaise, Didier; Maury, Sébastien; Deconinck, Eric; Tabrizi, Reza; Contentin, N; Mohty, Mohamad; Nguyen, Stéphanie; Lioure, Bruno; Raus, Nicole; Latour, Régis Peffault de; Yakoub-Agha, Ibrahim

doi:10.1038/bmt.2015.206

Cited by 12 publications

(10 citation statements)

References 10 publications

(11 reference statements)

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“…In the current study, we report the largest cohort of patients with BCR‐ABL1 ‐positive AML who received an alloSCT with a prolonged follow‐up, considering that this is an extraordinary rare entity. Despite previous reports in the literature indicating a very poor prognosis, with a median overall survival between 9–24 months, outcome of patients herein described was relatively favorable, especially in first CR1, with a OS of almost 60% at 5 years, and a relapse incidence of 36%, confirming the outcome of other studies performed in in recent years …”

Section: Discussionsupporting

confidence: 78%

“…Age (<50 years) and MRD status at transplant were the only prognostic factors identified in our study. Previous publications, although predominantly case reports and small series of patients largely confirm the significance of lower age and CR on a better outcome after allogeneic stem cell transplantation . These findings highlight the importance to achieve a deeper control of the disease before the transplant, and monitor molecularly defined MRD as the therapeutic objective in these patients, as proposed in BCR‐ABL1 B‐ALL and CML .…”

Section: Discussionmentioning

confidence: 75%

“…Nonetheless, there is a complete lack of evidence regarding many different aspects of treatment, such as the optimal TKI to be used in this context, best AML type chemotherapy to be combined with, or the role of maintenance therapy post‐transplant to prevent relapse . Case reports and small series in recent years showed favorable results after allogeneic SCT, as exemplified in the largest group of the patients with BCR‐ABL1 ‐positive AML who underwent alloSCT reported so far, with a remarkable 2‐year overall survival of 68% Therefore, our aim was to analyze the contemporary outcome of patients with BCR‐ABL1 ‐positive AML who underwent SCT in a recent time period, which might reflect the impact of the TKIs in the treatment of the disease, in the comprehensive EBMT database.…”

Section: Introductionmentioning

confidence: 99%

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Relatively favorable outcome after allogeneic stem cell transplantation for BCR‐ABL1‐positive AML: A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT)

Lazarevic

Labopin

et al. 2017

American J Hematol

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The aim of the study was to assess the role of allogeneic stem cell transplantation (SCT) in patients diagnosed with BCR-ABL1-positive acute myeloid leukemia (AML). Fifty-seven patients (median age, 48 years, range: 19-67) with BCR-ABL1 positive AML undergoing SCT were identified. The majority of the patients (70%) received a TKI before the transplant. At SCT 48 patients were in CR (45 in CR1), while 9 patients were transplanted in a more advanced stage of the disease. MRD was negative (BCR-ABL1/ABL < 10 ) at time of SCT in 36.1% (14/40). After SCT, 16 (61.5%) out of 26 patients with MRD positive at transplantation reached MRD negativity. After a median follow-up of 6.3 years (0.7-14.2), NRM, RI, LFS, OS, and GRFS at 5 years were 18.1%, 37%, 44.2%, 53.8%, and 32.1%, respectively. The cumulative incidence of acute GvHD grade II-IV was 16.4%, incidence of chronic GvHD 24.9%, and of extensive cGvHD 21.4%, respectively. In patients who received SCT in CR1, 5-yr NRM, RI, LFS, OS, and GRFS were 15.9%, 36.4%, 46.5%, 59.4%, and 34.9%, respectively. Univariate analysis showed that age (<50 vs. ≥50 years) was associated with RI (5-yr: 22.7 vs. 50%), LFS (5-yr: 61.9 vs. 31.8%), and GRFS (5-yr: 52.4 vs. 18.2%), whereas MRD-negative status before SCT was associated with an improved GRFS (38.9 vs. 16.7%). We conclude that the outcome of patients <50 years of age with BCR-ABL1-positive AML receiving allogeneic SCT in CR is relatively favorable, possibly reflecting the beneficial effect of the use of TKI.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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Relatively favorable outcome after allogeneic stem cell transplantation for BCR‐ABL1‐positive AML: A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT)

Lazarevic

Labopin

et al. 2017

American J Hematol

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“…Ph + AML diagnosis mostly depended on flow cytometry with cytogenetic evidence, specific maturation arrest morphology in bone marrow specimen, no history of antecedent blood anomaly, presence sign of myelodysplasia, p190 minor BCR/ ABL positivity, and clinical characteristics such as the absence of splenomegaly or peripheral blood basophilia [11]. Despite recent advances in gene sequencing techniques and knowledge, clinical evidence is still required to diagnose Ph + AML [8,11,17].…”

Section: Discussionmentioning

confidence: 99%

Impact of an Additional Chromosome on the Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome–Positive Acute Myeloid Leukemia in Adults

Min

Kim

Yoon

et al. 2018

Biology of Blood and Marrow Transplantation

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The incidence of Philadelphia chromosome positivity (Ph) in adults with acute myeloid leukemia (AML) is very low. Ph AML is considered to be high risk for failure to attain remission or for early relapse after standard chemotherapy. Because of the low incidence of the disease, it has been difficult to determine the best treatment, including the effects of tyrosine kinase inhibitors. We retrospectively analyzed 29 patients with Ph AML (median age, 45 years; range, 18 to 80) managed at our center between 2002 and 2016. Two patients were not treated at all, 3 received repeated low-dose cytarabine, and 24 were treated with 3 + 7 standard induction chemotherapy. All 27 treated patients also received interim imatinib 400 mg orally until the day of the next chemotherapy cycle began or as conditioning for allogeneic hematopoietic cell transplantation (HCT), which was performed in 17 patients. Of the 29 patients with Ph AML, 7 (24.1%) had additional inv(16), 3 of whom had therapy-related AML. In the 7 with inv(16), the median age was younger (31 versus 44 years, P = .083) and the complete remission (CR) rate was relatively higher (85.7% versus 54.5%, P = .214) than in those without inv(16). Among the 27 treated patients, 20 (74.1%) achieved CR after standard chemotherapy with interim imatinib and 2 (7.4%) achieved CR after low-dose cytarabine with interim imatinib. After a median follow-up of 65.5 months (range, 13.4 to 156.6), the 5-year overall survival (OS) among all 27 treated patients was 43.1%. For the 17 patients who underwent HCT the 5-year OS of 17 patients (10 in subgroup without inv(16) and 7 in subgroup with inv(16)) treated with allogeneic HCT was 69.3%. All 7 with inv(16) were still alive at the end of the study. In contrast, all patients not treated with HCT died within a median of 6.25 months (range, .2 to 18.2). Interim imatinib combined with chemotherapy yielded an acceptable remission rate in adult patients with Ph AML. Allogeneic HCT as a postremission therapy provided long-term disease control in two-thirds of those who underwent the transplant. We also demonstrated that inv(16) was related to a favorable outcome in Ph AML, including therapy-related AML.

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“…Philadelphia chromosome‐positive de novo AML is a rare condition with estimated incidence rate of 0.5–3% . The 2016 revision of the World Health Organization (WHO) classification has recognized mixed phenotype AML with t(9;22) as a separate entity .…”

Section: Discussionmentioning

confidence: 99%

Mixed phenotype acute leukemia with t(9;22): success with nonacute myeloid leukemia‐type intensive induction therapy and stem cell transplantation

Chan

Jamil

Millius

et al. 2017

Clinical Case Reports

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Allogeneic stem cell transplantation (allo-SCT) for de novo Ph+ AML: a study from the French Society of Bone Marrow Transplantation and Cell Therapy

Cited by 12 publications

References 10 publications

Relatively favorable outcome after allogeneic stem cell transplantation for BCR‐ABL1‐positive AML: A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT)

Relatively favorable outcome after allogeneic stem cell transplantation for BCR‐ABL1‐positive AML: A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT)

Impact of an Additional Chromosome on the Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome–Positive Acute Myeloid Leukemia in Adults

Mixed phenotype acute leukemia with t(9;22): success with nonacute myeloid leukemia‐type intensive induction therapy and stem cell transplantation

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