Improved Outcome in Early Induction Deaths in Patients with Acute Promyelocytic Leukemia After Therapeutic and Supportive Interventions: a Follow Up Study of Seven-years' Experience at a Tertiary Care Center

Introduction And Objectives: Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia with characteristic morphology and clinical features. Early mortality rate of 30% has been reported in developed countries despite prompt initiation of treatment. We have previously reported an early induction mortality of approximately 62% in our cohort. Based on this mortality rate, we made changes in our treatment protocol. The objective of this follow-up study was to report the early induction mortality and overall survival of patients with APL after incorporating changes in chemotherapy and supportive care regimen.

Subjects And Methods: This was a prospective descriptive study conducted at Aga Khan University Karachi, Pakistan from October 2012 till October 2019. Data of patients included clinical features, morphological findings, cytogenetic and PCR studies, cytotoxic protocols, overall outcome and causes of early induction mortality. The changes in treatment protocol included prophylactic infusion of fresh frozen plasma, dexamethasone therapy and other changes in supportive care regimen. Results were recorded as frequencies and percentages. Statistical Package for the Social Sciences version 19.0 (SPSS Inc., Chicago, IL, USA) was used to analyze patient's data. Survival curves were calculated using the Kaplan-Meier method.

Results: During the study period, total of 447 patients presented with acute myeloid leukemia at our institution out of which 40 patients were diagnosed with acute promyelocytic leukemia (9%). Out of these 40 patients 24 were males and 16 were females. The median age was 37 years. Twenty-five patients were in low risk group whereas 15 were high-risk. Differentiation syndrome was seen in 14 patients. As a part of induction chemotherapy, 13 patients received only ATRA because they were not eligible for chemotherapy and 17 patients received a combination of ATRA and anthracycline. Among the remaining patients, four received ATRA, arsenic and anthracycline while two received ATRA and arsenic only. Four patients did not receive any treatment because of rapid deterioration of clinical condition and death. The overall survival was 65% and early induction mortality was 30%.

Conclusion: The early induction mortality decreased to 30% from 62% in this study and the overall survival was 65%. With the introduction of prophylactic infusion of fresh frozen plasma, dexamethasone and appropriate supportive treatment during the induction chemotherapy, we were able to improve the induction mortality and overall survival of patients.