Philadelphia chromosome-positive acute lymphoblastic leukemia with an e14a3 BCR-ABL1 fusion: The role of molecular monitoring

The concurrent administration of tyrosine kinase inhibitors (TKIs) with standard chemotherapy together with allogeneic hematopoietic stem cell transplantation (alloHSCT) has improved the outcome of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Although to date, no study has shown alloHSCT to be inferior to chemotherapy plus TKIs in any subgroup of adult Ph+ ALL, there is some evidence suggesting no additional benefit of alloHSCT in patients with deep molecular responses to intensive chemotherapy with a second-generation, and especially, third-generation TKI. As none of these positive and negative studies are controlled, randomized trials are needed to fully define the role of alloHSCT in Ph+ ALL, especially in those with deep molecular response. However, if studies combining TKIs with new approaches such as immunotherapy lead to durable responses, alloHSCT in the first complete remission could be avoided in the near future in the majority of patients with Ph+ ALL.

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The Role of Imatinib in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Clinical Medicine Reviews in Oncology ◽

10.4137/cmro.s1604 ◽

2010 ◽

Vol 2 ◽

pp. 69-77

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Philadelphia Chromosome Positive

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Minimal residual disease–based role of imatinib as a first-line interim therapy prior to allogeneic stem cell transplantation in Philadelphia chromosome–positive acute lymphoblastic leukemia

Blood ◽

10.1182/blood-2003-04-1180 ◽

2003 ◽

Vol 102 (8) ◽

pp. 3068-3070 ◽

Cited By ~ 28

Author(s):

Seok Lee ◽

Dong-Wook Kim ◽

Yoo-Jin Kim ◽

Nak-Gyun Chung ◽

Yoo-Li Kim ◽

...

Keyword(s):

Stem Cell ◽

Acute Lymphoblastic Leukemia ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

First Line ◽

Philadelphia Chromosome Positive

Abstract Fourteen adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) were studied to evaluate the role of imatinib prior to allogeneic stem cell transplantation (SCT). Of these, 12 patients were in complete hematologic response (CHR), and 2 were refractory. Imatinib was administered as an interim schedule after each chemotherapy course. After the first imatinib cycle, 11 patients remained in sustained CHR with a decrease in the BCR-ABL/ABL ratios (0.89 logs), and one refractory patient achieved CHR. Meanwhile, 2 patients were resistant to imatinib. Ten patients receiving a second imatinib cycle following consolidation showed sustained CHR, including 2 molecular CR, with a further decrease in the BCR-ABL/ABL ratios (0.19 logs). Twelve patients underwent SCT in a favorable status, and of these, 11 are still alive in a leukemia-free status at 9 to 28+ months after SCT. First-line imatinib interim therapy appears to be a useful strategy to bridge the time to SCT for patients with Ph+ ALL.

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Molecular Monitoring in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia with the Variant e13a3 BCR-ABL1 Fusion

Case Reports in Hematology ◽

10.1155/2019/9635070 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Mireille Crampe ◽

Laura Kearney ◽

David O’Brien ◽

C. Larry Bacon ◽

Derville O’Shea ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Response To Therapy ◽

Molecular Monitoring ◽

Transcript Levels ◽

Disease Response ◽

Small Minority ◽

Distinct Phenotype ◽

Philadelphia Chromosome Positive

Monitoring BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a widely adopted method to assess response to therapy. However, a small minority of Ph+ ALL patients express variant BCR-ABL1 transcript types, usually due to splicing of alternative BCR or ABL1 exons. Whether patients expressing these rare, variant BCR-ABL1 transcripts have a distinct phenotype or response to therapy is not known due to the limited number of reported cases. Here, we report the presenting features of Ph+ ALL in a young adult with a variant e13a3 BCR-ABL1 fusion. Molecular monitoring reflected the disease response from diagnosis through allogeneic stem cell transplantation which resulted in undetectable e13a3 BCR-ABL1 transcripts. This case highlights the value of molecular monitoring in Ph+ ALL patients with variant BCR-ABL1 transcripts and the requirement for standardization of such assays.

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