Childhood acute lymphoblastic leukemia in India: An approach to managementin a three‐tier society

Abstract

Within a population of 882 million, six thousand children will develop acute lymphoblastic leukemia each year in India. These children come from three socio-economic backgrounds: Profile I (70%) being extremely poor who cannot afford any treatment unless it is provided free, Profile II (25%) from the middle class, and Profile III (5%) who can afford to have the best possible treatment. Current protocols for childhood ALL range from simple low-cost regimes like UKALL VIII, intermediate intensity regimes like BFM 76/79, and aggressive regimes aimed at increasing cure rates in the high risk groups. Since state resources are limited, the pediatric oncologist in India has to decide on the appropriate treatment protocol for the individual child in each of these profiles. This paper suggests an approach to managing childhood ALL in developing countries like India.

Stem cell transplantation in India

“…1 With 20 million carriers for thalassemia and 10 000 children being born with thalassemia major each year, if one-third of these patients have an HLA-matched sibling donor, there is a potential to cure 3000 children with BMT. 2 If one considers six per million as the incidence of aplastic anemia, there would be 6000 new cases/year, and if 10% of these patients are suitable candidates for transplant, then the country would need to do 600 transplants per year for this disease alone.…”

Adult ALL: treatment outcome and prognostic factors in an Indian population using a modified German ALL (GMALL) protocol

“…However, in developing countries where state funding for expensive health-care interventions is lacking, it is important that treatment modifications should be cost effective. 5 This is a retrospective analysis of the outcome of 210 adult patients with ALL (X15 years) treated with a modified German ALL (GMALL) protocol from 1994 to 2003. The aim of this study was to identify biologic and clinical prognostic markers for adult ALL in the Indian population and compare this with Caucasian data.…”

“…2 We have previously reported that the expression of FRb is limited to the myelomonocytic lineage and that its expression is increased during neutrophil maturation and during the activation of macrophage; 3,4 however, among normal hematopoietic cells, only the receptor expressed in activated macrophage is functional in having the ability to bind folate. 4,5 FRb is also expressed in a functional form in approximately 70% of acute myelogenous leukemia (AML) in which it is frequently coexpressed with CD34. 6 These observations suggest that FRb is a potential target for drug delivery to AML cells, but prospects of its clinical utility are limited by the variable and the frequently low expression of the receptor in the leukemic cells of AML patients.…”

“…6 Our previous in vitro studies in both AML cell lines and primary AML cells have demonstrated that all-trans retinoic acid (ATRA) acts directly on the FRb gene to selectively upregulate its expression 6,7 and that this effect is potentiated by innocuous histone deacetylase (HDAC) inhibitors, including valproic acid (VPA). 8 The receptor induction sensitized AML cells to FRtargeted drugs including folate-coated liposomal doxorubicin 5 and the antifolate, dideazatetrahydrofolate. 8 Treatment with ATRA also increased the survival of mice that were injected KG1 AML cells in their peritoneal cavity upon treatment with FR-targeted liposomal doxorubicin.…”

“…8 Treatment with ATRA also increased the survival of mice that were injected KG1 AML cells in their peritoneal cavity upon treatment with FR-targeted liposomal doxorubicin. 5 Combination treatment with innocuous agents that upregulate FRb in AML cells is, therefore, an attractive means of addressing a major limitation of experimental FR-targeted therapies in AML.…”