What is the outcome of children with Acute Lymphocytic Leukemia (ALL) in India?

The answer to this question, depends on whose asking it and to what purpose. At an individual level (when access to treatment is not a barrier), currently the standard 5-year survival in most of the developed world is 80-90% with that for low-risk ALL even higher than 90%. The best published results from India are 59% 5-year survival for children with ALL treated from 1985 to 2003 in CMC Vellore (Bajel et al, 2008), and of 57% in those treated from 1990 to 1993 in Tata Memorial Hospital, Mumbai (Advani et al, 1999). For low-risk ALL, these survival figures are around 73-77%. It is important to point out, that these results from India are calculated after censoring (removing) those children with ALL who refused to start treatment or abandoned ongoing active treatment. There are some unpublished data suggesting better outcomes - 70% 4-year survival of children with ALL treated at Sir Ganga Ram Hospital in Delhi (Sachdeva et al, SIOP 2007); and 94% survival after median follow-up of two years of children with ALL treated at Apollo Hospital in Delhi (Mahajan et al, SIOP 2008). A more accurate reflection of outcomes of children with ALL in India can be obtained when we include all those who refused and abandoned treatment and then calculate the survival. This is particularly relevant to clinicians, epidemiologists and health planners. To my knowledge, the recent paper from PGI in Chandigarh is the only one to publish such data. It shows a 4-year overall survival of 33% and a 10-year overall survival of 30% for children with ALL diagnosed at that institute from 1990 to 2006 (Kulkarni et al, 2009). Other sources of such information are the population-based cancer registries. Only two reports have ever been published looking at population-based 5-year survival in children with cancer and these were 35% from Bangalore for the period 1982 to 1987 (Nandakumar et al, 1996); and 39% for Chennai for the period 1990 to 2001 (Swaminathan et al, 2008). In a nutshell, 6 out of 10 children with ALL in India will have long term survival (and cure) if they are compliant with their treatment. If treatment uptake and compliance is variable, only 1 out of 3 children in such settings would be cured. These outcomes apply only to those treated in specialist tertiary centres in urban areas. For those in rural areas or non-specialist centres, the outlook is certain to be worse.

Vincristine Neurotoxicity and Malnutrition

Vincristine is an important weapon in the chemotherapeutic arsenal against several childhood cancers including acute lymphoblastic leukaemia, lymphomas, Wilm's tumour and various brain tumours. It does have side-effects, notable neurotoxicity which manifests in various ways. It is accepted that malnutrition (more common in resource-poor nations) can exacerbate vincristine-related neurotoxicity.

A report from Delhi highlights the prevalence of vincristine-related neurotoxicity (at dose of 1.4 mg/m2) which was seen in 10 out ot 20 children with various cancers treated over a two year period (Ref - Gomber et al, Indian J Pediatrics, Jan 2010). This is much higher than that reported from resource-rich nations. In 6 cases, the severity of the toxicity warranted temporary discontinuation of the drug. The weight of all patients who developed neurotoxicity was below the 3rd centile for age and was significantly lower than those children who did not develop neurotoxicty.

Clues to the mechanism by which malnutrition can increase vincristine-related neurotoxicity can be found in another recent paper (ref - Israel et al, European Journal of Cancer, 2010). The pharmacockinetics of vincristine (at dose of 1.5 mg/m2) were studied in 11 children with Wilm's tumour from Malawi and 8 children from UK. The children from Malawi had significantly lower weight-for-height than those in UK. The clearence of vincristine was significantly slower in Malawian children and as a result the exposure to vincristine (measured by area under the curve) was almost two times longer. There was a linear corelation between the extent of malnutrition and the area under the curve for vincristine.

The above two studies would suggest that in children with cancer who are malnourished, we may have to reconsider the dose of vincristine. Clearly, this area merits more research in India and in other resource-poor settings.