Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia in the Era of Novel Agents and Targeted Therapies

Al-Anazi Ka

doi:10.21767/2575-7725.100018

Abstract

The outcomes of adult patients with acute lymphoblastic leukemia have improved significantly due to the recent advances in diagnostics and in therapeutic interventions. The adoption of pediatric chemotherapeutic regimens in adolescents and young adults, the availability of several novel and targeted therapies, and the provision of safer modalities of stem cell transplants have yielded higher response rates and improved survival. This review article will be a recent update on the role of hematopoietic stem cell transplantation in adults with acute lymphoblastic leukemia in the era of novel agents and targeted therapies. Various modalities of stem cell therapies in different subtypes of acute lymphoblastic leukemia in addition to various modalities of novel therapies will also be discussed thoroughly.

Highlights

Acute lymphoblastic leukemia (ALL), a clonal expansion or malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites, is a highly heterogeneous disease comprising several entities that have distinct clinical manifestations, therapeutic strategies and prognostic implications [1,2].Worldwide, different induction chemotherapeutic regimens are utilized in the treatment of adult patients with ALL [3,4,5,6]
The more intensified pediatric ALL chemotherapeutic regimens have been adopted in adolescents and young adults (AYAs), 15-40 years of age, having ALL and their use has been associated with superior response rates compared with the traditional adult regimens of chemotherapy [3,5,8]
The most common chromosomal abnormalities that are encountered in patients with ALL include: (1) Philadelphia chromosome (t 9,22), (2) chromosomal abnormalities that are associated with higher risk of central nervous system involvement such as: t 4,11; t 8,14 and t 14q+, (3 ) chromosomal abnormalities that are associated with high white cell and blast cell counts at presentation and high risk of relapse such as: t 9,22 and t 4,11, and (4) other common cytogenetic abnormalities that are encountered in patients with ALL include: t 10,14; t 1,14; deletion 11q22; deletion 11q23; hypodiploidy and hyperdiploidy [2,9,10,11,12]

Summary

Introduction

Acute lymphoblastic leukemia (ALL), a clonal expansion or malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites, is a highly heterogeneous disease comprising several entities that have distinct clinical manifestations, therapeutic strategies and prognostic implications [1,2]. Indications of allogeneic HSCT in adults with ALL include: (1) Ph+ ALL in CR1, (2) ALL with Ph-like molecular signature, (3) HR or very HR ALL in CR1, (4) relapsed ALL (ALL in CR2 or beyond), (5) primary refractory disease (ALL refractory to induction or first-line chemotherapy), after achievement of CR following salvage therapy, (6) presence of MRD at any stage during the course of the disease, regardless their initial risk group (SR or HR), and (7) MLL (mixed lineage leukemia) gene rearrangement [51,52,53,54,55,56,57,58,59,60,61,62]. Obintuzumab, Ofatumomab, Epratuzumab, Inotuzumab Ozogamicin, Gemtuzumab Ozogamicin, Moxetumomab Pasudodotox, Coltuximan Ravtansine (Sar3419), Denintuzumab Mefodotin (Gn-Cd19a), Adc-402, Combotox (Anti- Cd19 And Anti- Cd22) And Blinatumomab (Anti- Cd3; Cd 19 Construct)

20. Liposomal and pegylated compounds

Findings

Conclusions and Future Directions