Complete Hematologic Response to Low-Intensity Treatment in Philadelphia Chromosome Positive (+) B Cell Acute Lymphoblastic Leukemia

Authors' Affiliations

Elizabeth Corinne Brien, Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN Alicia Schmitt, Department of Medicine, University of Medicine Rostock, Rostock, Mecklenburg-Vorpommern, Germany Parisa Toosi, Department of Pathology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN

Location

D.P. Culp Center Ballroom

Start Date

4-5-2024 9:00 AM

End Date

4-5-2024 11:30 AM

Poster Number

5

Name of Project's Faculty Sponsor

Devapiran Jaishankar

Faculty Sponsor's Department

Internal Medicine

Classification of First Author

Medical Resident or Clinical Fellow

Competition Type

Non-Competitive

Type

Poster Presentation

Presentation Category

Health

Abstract or Artist's Statement

Philadelphia Chromosome positive B Cell Acute Lymphoblastic Leukemia (Ph+ ALL) previously carried a poor prognosis for frail, elderly patients with significant comorbidities. Today, induction regimens employing potent second-generation tyrosine kinase inhibitors (TKIs) such as dasatinib offer robust activity against the BCR-ABL tyrosine kinase and have produced reductions in tumor burden consistent with higher intensity induction regimens, which typically require at least a year of maintenance with chemotherapy afterwards. We herein present a case of Ph+ ALL in a 78-year-old male with multiple comorbidities including congestive heart failure, atrial fibrillation, mechanical aortic valve on anticoagulation, and venous insufficiency. He initially presented with neck pain, leukocytosis, and anemia, with outpatient peripheral smear notable for 35% lymphoblasts involving peripheral blood consistent with ALL. Inpatient diagnostic bone marrow biopsy showed 70% involvement by B-lymphoblasts, and Fluorescent in Situ Hybridization (FISH) confirmed the presence of the BCR-ABL fusion gene at p190 locus. Following four weeks of induction therapy with Vincristine, dose-reduced dasatinib, and dexamethasone, peripheral blood BCR-ABL reverse-transcriptase polymerase chain reaction (RT-PCR) transcripts were down to 0.2% from an initial 29%. Subsequent weekly maintenance intrathecal methotrexate (MTX)/cytarabine was initiated with continued daily, dose reduced Dasatinib (70mg) due to side effects. After six weeks, peripheral blood RT-PCR transcripts were undetectable and subsequent bone marrow biopsy revealed no morphology or immunophenotype of B-ALL, with complete cytogenetic response (CCyR), and BCR/ABL RT-PCR transcripts reduced to 0.05%. Given this patient’s age and comorbidities, we opted for a conservative treatment approach with the intent of disease control. Despite the significant blast count in the bone marrow at time of diagnosis, complete hematologic remission (CHR) and CCyR were achieved with a 3-drug induction therapy regimen of Vincristine/Dasatinib/Dexamethasone compared to the typical 4-drug induction combinations that can include anthracyclines or high dose methotrexate. By reporting the success of this case, we aim to add further data to the literature supporting the use of dasatinib plus dexamethasone as the backbone of low intensity induction therapy for frail, elderly patients with Ph+ ALL. Ph+ ALL is most common in adults ages 50-70 years old. The GIMEMA LAL1205 study of dasatinib combined with steroids followed by intrathecal chemotherapy (MTX) showed 100% CHR and 52.1% having minimal residual disease (MRD) with three log reductions in BCR-ABL levels after induction therapy. This study demonstrated the significance of achieving complete remission by day 22 of induction therapy, which was concluded to be predictive of DFS. The EWALL-PH-01 study demonstrated the validity of a low-intensity induction regimen consisting of dasatinib, dexamethasone, and vincristine by demonstrating 96% CHR at the end of induction therapy. It further demonstrated the efficacy, safety, and tolerable nature of dasatinib as the TKI of choice for adult patients with Ph+ ALL at least 55 years of age with significant comorbidities. Our approach along the lines of this trial shows the ability to achieve the hematologic parameters necessary for long-term survival in elderly patients without intensive therapy.

This document is currently not available here.

Share

COinS
 
Apr 5th, 9:00 AM Apr 5th, 11:30 AM

Complete Hematologic Response to Low-Intensity Treatment in Philadelphia Chromosome Positive (+) B Cell Acute Lymphoblastic Leukemia

D.P. Culp Center Ballroom

Philadelphia Chromosome positive B Cell Acute Lymphoblastic Leukemia (Ph+ ALL) previously carried a poor prognosis for frail, elderly patients with significant comorbidities. Today, induction regimens employing potent second-generation tyrosine kinase inhibitors (TKIs) such as dasatinib offer robust activity against the BCR-ABL tyrosine kinase and have produced reductions in tumor burden consistent with higher intensity induction regimens, which typically require at least a year of maintenance with chemotherapy afterwards. We herein present a case of Ph+ ALL in a 78-year-old male with multiple comorbidities including congestive heart failure, atrial fibrillation, mechanical aortic valve on anticoagulation, and venous insufficiency. He initially presented with neck pain, leukocytosis, and anemia, with outpatient peripheral smear notable for 35% lymphoblasts involving peripheral blood consistent with ALL. Inpatient diagnostic bone marrow biopsy showed 70% involvement by B-lymphoblasts, and Fluorescent in Situ Hybridization (FISH) confirmed the presence of the BCR-ABL fusion gene at p190 locus. Following four weeks of induction therapy with Vincristine, dose-reduced dasatinib, and dexamethasone, peripheral blood BCR-ABL reverse-transcriptase polymerase chain reaction (RT-PCR) transcripts were down to 0.2% from an initial 29%. Subsequent weekly maintenance intrathecal methotrexate (MTX)/cytarabine was initiated with continued daily, dose reduced Dasatinib (70mg) due to side effects. After six weeks, peripheral blood RT-PCR transcripts were undetectable and subsequent bone marrow biopsy revealed no morphology or immunophenotype of B-ALL, with complete cytogenetic response (CCyR), and BCR/ABL RT-PCR transcripts reduced to 0.05%. Given this patient’s age and comorbidities, we opted for a conservative treatment approach with the intent of disease control. Despite the significant blast count in the bone marrow at time of diagnosis, complete hematologic remission (CHR) and CCyR were achieved with a 3-drug induction therapy regimen of Vincristine/Dasatinib/Dexamethasone compared to the typical 4-drug induction combinations that can include anthracyclines or high dose methotrexate. By reporting the success of this case, we aim to add further data to the literature supporting the use of dasatinib plus dexamethasone as the backbone of low intensity induction therapy for frail, elderly patients with Ph+ ALL. Ph+ ALL is most common in adults ages 50-70 years old. The GIMEMA LAL1205 study of dasatinib combined with steroids followed by intrathecal chemotherapy (MTX) showed 100% CHR and 52.1% having minimal residual disease (MRD) with three log reductions in BCR-ABL levels after induction therapy. This study demonstrated the significance of achieving complete remission by day 22 of induction therapy, which was concluded to be predictive of DFS. The EWALL-PH-01 study demonstrated the validity of a low-intensity induction regimen consisting of dasatinib, dexamethasone, and vincristine by demonstrating 96% CHR at the end of induction therapy. It further demonstrated the efficacy, safety, and tolerable nature of dasatinib as the TKI of choice for adult patients with Ph+ ALL at least 55 years of age with significant comorbidities. Our approach along the lines of this trial shows the ability to achieve the hematologic parameters necessary for long-term survival in elderly patients without intensive therapy.