Effectiveness of modified hyper-CVAD chemotherapy regimen in the treatment of adult acute lymphoblastic leukemia: a retrospective experience.

Hasan Jalaeikhoo,Mohammad Zokaasadi,Mohsen Rajaeinejad,Manoutchehr Keyhani,Mohammad Mehdi Dehghani Firoozabadi

doi:10.1002/cam4.1328

Abstract

Several chemotherapy regimens have been developed for the treatment of acute lymphoblastic leukemia (ALL), but relapse still presents the most common obstacles to attaining long‐term survival. The hyper‐CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and prednisolone)/HD MTX and Ara‐C (high‐dose methotrexate and cytarabine) chemotherapy regimen was first started in the MD Anderson Cancer Center as an intensive regimen for adult patients with ALL. The purpose of this study was to evaluate the effectiveness of a modified hyper‐CVAD protocol. We used hyper‐CVAD as consolidation/maintenance after remission induction with daunorubicin, vincristine, and prednisolone (and cyclophosphamide for T‐cell ALL only) rather than standard hyper‐CVAD in order to reduce treatment complications. This study was conducted as a retrospective review of medical records of ALL patients at 501 army hospital, Tehran, Iran, from 2005 to 2015. Three hundred and one patients underwent modified hyper‐CVAD chemotherapy regimen. Complete remission and overall survival (OS) rates were measured as primary endpoints. Two hundred and forty‐six (81.7%) reached complete remission (CR) during the first 6 months of treatment, and 55 patients (18.3%) did not reach CR. The 5‐year OS rate was 51.8% (95% CI (confidence interval): 45.1–57.8%). Modified hyper‐CVAD regimen is an efficient intensive chemotherapy regimen for consolidation/maintenance of adults with newly diagnosed ALL and has an acceptable 5‐year overall that is comparable to standard hyper‐CVAD regimen.

Highlights

Acute lymphoblastic leukemia (ALL) is a hematological malignancy with different pathological subtypes; Pre-B -cell ALL, pre-T -cell ALL, T-cell ALL, and B-cell ALL [1]
Despite advances in the treatment of acute lymphoblastic leukemia including different types of chimeric antigen receptor (CAR) T-cells, monoclonal antibodies like epratuzumab and bispecific T-cell engagers (BiTEs) such as blinatumomab [10], its current state in Iran has not changed dramatically over the past 25 years, and outcomes remain disappointing because of low survival in older adults, very expensive care even after remission and relapses with no apparent reason
More intensive chemotherapy regimens have been administered for the ALL patients to overcome the disease, but they have greater toxicity and more side effects and higher mortality rates

Summary

Introduction

Acute lymphoblastic leukemia (ALL) is a hematological malignancy with different pathological subtypes; Pre-B -cell ALL (the most common subtype), pre-T -cell ALL, T-cell ALL, and B-cell ALL [1]. Several chemotherapy regimens have been used and developed in the treatment of ALL. The most effective chemotherapy regimen in the treatment of adult ALL is not yet clear. The most widely used protocols were cancer and leukemia group B (CALGB) program which consisted of a five-agent combination, Group for Research on Adult Acute Lymphoblastic Leukemia 2003 (GRAALL 2003). Protocol and more recently hyper-C VAD [2, 3]. The hyper-CVAD regimen (hyperfractionated cyclophosphamide, vincristine, doxorubicin [Adriamycin], and dexamethasone)/HD MTX and Ara-C (high-dose methotrexate and cytarabine) are used widely in many institutions [5, 6]. The MD Anderson Cancer Center (MDACC) study reported a complete response (CR) rate of 92%, 5-year overall survival of 38% and progression-free survival (PFS) of 66% for adult patients with ALL [7, 8]

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