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

Lazarevic, Vladimir; Labopin, Myriam; Wu, Depei; Yakoub-Agha, Ibrahim; Huynh, Anne; Ljungman, Per; Schaap, Nicolaas; Cornelissen, Jan J.; Maillard, Natacha; Pioltelli, Pietro; Gedde‐Dahl, Tobias; Lenhoff, Stig; Houhou, Mohamed; Esteve, Jordi; Mohty, Mohamad; Nagler, Arnon

doi:10.1002/ajh.24928

Cited by 18 publications

(13 citation statements)

References 27 publications

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“…The CR rate of 75.9% and the deep molecular response rate as shown by RQ-PCR reflect the successful incorporation of a TKI into standard AML chemotherapy, which therefore can be used as bridging therapy to allogeneic HCT. Similar to our findings, a previous study also showed that pre-HCT MRD negativity was associated with a lower relapse rate and better survival [18].…”

Section: Discussionsupporting

confidence: 92%

“…However, a recently published study that retrospectively analyzed the registry of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation noted 18 patients treated with a TKI after HCT either as maintenance therapy or treatment for relapse. Hematologic relapse after allogeneic HCT occurred early, with a median interval of nearly 4 months post-HCT [18].…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 92%

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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“…These differences may be related to the different MRD levels in each study. The rate of treatment with TKI before allo-HCT in our study was similar to that reported in a previous study [8] (77.8% and 70.5%, respectively). The MRD-negative status was previously noted in 12 of the 29 patients treated with TKI before allo-HCT and in only one of the six patients not treated with TKI [8].…”

Section: Discussionsupporting

confidence: 91%

Allogeneic hematopoietic cell transplantation for acute myeloid leukemia with BCR::ABL1 fusion

Mizuno,

Takami,

Kawamura

et al. 2024

eJHaem

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BCR::ABL1 fusion is found in < 1% of de novo acute myeloid leukemia (AML) cases and confers a poor prognosis. This Japanese nationwide survey analyzed patients with AML (n = 22) and mixed phenotype acute leukemia (MPAL) (n = 10) with t(9;22) or BCR::ABL1 who underwent allogeneic hematopoietic cell transplantation (allo‐HCT) between 2002 and 2018. The 3‐year overall survival (OS) rates were 81.3% and 56.0%, respectively (p = 0.15), and leukemia‐free survival (LFS) rates were 76.2% and 42.0%, respectively (p = 0.10) in patients with AML and MPAL. The relapse rates were 9.5% and 14.0% (p = 0.93), and the non‐relapse mortality (NRM) rates were 14.3% and 44.0%, respectively (p = 0.10) in patients with AML and MPAL. One in 17 patients with AML, with pre‐transplant tyrosine kinase inhibitors (TKI), and three in five patients with AML, without pre‐transplant TKI, did not achieve complete remission (CR) before allo‐HCT (p = 0.024). Among the 20 patients with known disease status after allo‐HCT, 95.0% were in hematological or molecular CR. None of the four patients who received post‐transplant TKI for prophylaxis or measurable residual disease relapse experienced hematological relapse. In conclusion, our results suggest that pre‐transplant TKI could improve disease status before allo‐HCT. Moreover, allo‐HCT resulted in high OS, high LFS, low relapse, and low NRM rates in patients with AML with BCR::ABL1.

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“…In fact, the patients with BCR-ABL1 positive AML are often refractory to chemotherapy while the responses to imatinib are of limited duration [12]. A recent paper has reported that allogenic stem cell transplantation (allo-SCT) may improve outcome of younger patients [13]; however, given the small number of cases, the optimal therapy for AML with BCR-ABL1 has not been established yet. Beside common BCR-ABL1 transcripts, unusual transcripts have been also described in CML and acute leukemias.…”

Section: Discussionmentioning

confidence: 99%

A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: case report and literature review

et al. 2019

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BackgroundPhiladelphia (Ph) chromosome results from the reciprocal translocation t(9;22)(q34.1;q11.2) and is diagnostic for chronic myeloid leukemia (CML). However, this translocation is also found in acute lymphoid leukemia (ALL), as well as in rare cases of acute myeloid leukemias (AML). Most patients with CML harbor either the e13a2 or the e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. Moreover, several atypical BCR-ABL1 transcripts, beside the most common e1a2, e13a2 and e14a2, have been described, mainly in patients with CML. However, ALL and de novo AML may also carry BCR-ABL1 atypical transcripts which will confer a poor prognosis.Case presentationA 78-years old male was admitted at our hospital with clinical and laboratory features allowing to make the diagnosis of AML. No evidence of a preceding CML (splenomegaly or basophilia) was found. The karyotype on G-banded metaphases was 46,XY, t(9;22)(q34;q11). While the molecular analysis was ongoing, the patient started treatment based on hydroxyurea followed by 5-aza-2′-deoxycytidine. The molecular biology analysis revealed the simultaneous presence of the common p190 e1a2 and the rare e6a2 isoforms. Because of persistent pancytopenia and presence of blasts, according to the molecular data, he was then switched to tyrosine kinase inhibitors (TKIs) treatment. Nevertheless, after 2 months, the patient was still refractory to second line treatment dying because of a pulmonary infection.ConclusionThe atypical p190 e6a2 transcript seems to be associated in AML with aggressive disease. TKI therapy alone does not seem to control the disease. Prompt observations on these patients carrying rare BCR-ABL1 transcripts may help to establish optimal treatment approaches on these aggressive BCR-ABL1 phenotypes in different setting of patients.

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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)

Cited by 18 publications

References 27 publications

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

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

Allogeneic hematopoietic cell transplantation for acute myeloid leukemia with BCR::ABL1 fusion

A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: case report and literature review

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