Acute Lymphoblastic Leukemia Progress
in Developing World
Suresh H. Advani
Jaslok Hospital & Research Center, Mumbai
The tremendous progress in the treatment of childhood acute lymphoblastic leukemia
is the true success story of pediatric oncology. From the 1960s when cure rates
were a dismal 15-20%, we have come to an era where the five year disease-free
survival has reached 75-80%. Advances in all spheres of diagnostics and therapeutics
have contributed to this success. The rational use of combination chemotherapy,
central nervous system prophylaxis, advances in supportive care, including the
availability of safe blood products, use of long-term central venous access
devices and potent antibiotics have all played a key role in this achievement.
The understanding that ALL is a heterogeneous disease led to risk stratification
of therapy. Today, patients with low-risk disease can be treated with minimal
therapy with the aim of decreasing late effects, and high-risk patients can
be identified upfront and given intensive therapy. Unfortunately India is lagging
behind the West in this success story. The MCP841 protocol is a multi-center
protocol designed especially for developing countries and was initiated in the
mid-1980s in three centers in Mumbai, Delhi and Chennai. It is still being used
in many premier institutes in the country. Early results with this protocol
showed five year event-free survival of 50%. This gradually improved to 60%
by the end of the 1990s. There is still a survival gap of 20% between the West
and our country. Several factors have been hypothesized to account for this
gap, one of the most important being the difference in the biology of the disease
in these two regions. Most Western literature quotes the incidence of T cell
ALL to be around 10-15%. In the early eighties, the incidence of T-cell ALL
was reported to be as high as 50% in Chennai in Southern India, and 38% and
33% in Delhi and Mumbai, respectively. This high incidence has decreased in
the last two decades. By the end of the nineties it was 37% in Chennai and 30%
and 20% in Delhi and Mumbai, respectively. Economic development has been proposed
as the probable cause of this changing immunophenotypic pattern. With economic
growth and better health care, children are surviving infections early in life
to face the subsequent immunologic stimuli of recurrent infections, both clinical
and subclinical. This could lead to the emergence of the common ALL clone. Similarly,
the presence of a TEL-AML1 translocation, which is a good prognostic marker
in ALL, is reported in 35% of patients in the West, but is present in less than
10% of Indian patients. This may be partly responsible for the poorer treatment
outcome. Keeping the differences in biology in mind, the next multicenter treatment
protocol will be more aggressive and will study the significance of biological
characteristics of ALL to outcome, with the aim of stratifying treatment accordingly.
The tremendous progress in the treatment of childhood acute lymphoblastic leukemia
is the true success story of pediatric oncology. From the 1960s when cure rates
were a dismal 15-20%, we have come to an era where the five year disease-free
survival has reached 75-80%. Advances in all spheres of diagnostics and therapeutics
have contributed to this success. The rational use of combination chemotherapy,
central nervous system prophylaxis, advances in supportive care, including the
availability of safe blood products, use of long-term central venous access
devices and potent antibiotics have all played a key role in this achievement.
The understanding that ALL is a heterogeneous disease led to risk stratification
of therapy. Today, patients with low-risk disease can be treated with minimal
therapy with the aim of decreasing late effects, and high-risk patients can
be identified upfront and given intensive therapy. Unfortunately India is lagging
behind the West in this success story. The MCP841 protocol is a multi-center
protocol designed especially for developing countries and was initiated in the
mid-1980s in three centers in Mumbai, Delhi and Chennai. It is still being used
in many premier institutes in the country. Early results with this protocol
showed five year event-free survival of 50%. This gradually improved to 60%
by the end of the 1990s. There is still a survival gap of 20% between the West
and our country. Several factors have been hypothesized to account for this
gap, one of the most important being the difference in the biology of the disease
in these two regions. Most Western literature quotes the incidence of T cell
ALL to be around 10-15%. In the early eighties, the incidence of T-cell ALL
was reported to be as high as 50% in Chennai in Southern India, and 38% and
33% in Delhi and Mumbai, respectively. This high incidence has decreased in
the last two decades. By the end of the nineties it was 37% in Chennai and 30%
and 20% in Delhi and Mumbai, respectively. Economic development has been proposed
as the probable cause of this changing immunophenotypic pattern. With economic
growth and better health care, children are surviving infections early in life
to face the subsequent immunologic stimuli of recurrent infections, both clinical
and subclinical. This could lead to the emergence of the common ALL clone. Similarly,
the presence of a TEL-AML1 translocation, which is a good prognostic marker
in ALL, is reported in 35% of patients in the West, but is present in less than
10% of Indian patients. This may be partly responsible for the poorer treatment
outcome. Keeping the differences in biology in mind, the next multicenter treatment
protocol will be more aggressive and will study the significance of biological
characteristics of ALL to outcome, with the aim of stratifying treatment accordingly.