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Acute lymphoblastic leukemia in India: an analysis of prognostic factors using a single treatment regimen
Insights
This study improved treatment outcomes for Indian children with acute lymphoblastic leukemia (ALL) using an intensive protocol. Key prognostic factors identified were white blood cell count, hemoglobin, and lymphadenopathy, improving event-free survival.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Research
Background:
- Treatment outcomes for acute lymphoblastic leukemia (ALL) in Indian children have historically been poor.
- Potential differences in ALL subtype patterns between India and Western countries may influence outcomes.
- An intensive treatment protocol (MCP841) was implemented to improve survival and identify prognostic factors.
Purpose of the Study:
- To evaluate the efficacy of the intensive MCP841 treatment protocol for pediatric ALL in India.
- To identify significant prognostic factors influencing treatment outcomes in this patient population.
- To improve event-free survival (EFS) rates in children with ALL.
Main Methods:
- A total of 530 previously untreated pediatric ALL patients (<25 years) were enrolled.
- Treatment involved three induction, consolidation, and six maintenance cycles over two years.
- Central nervous system (CNS) prophylaxis included cranial irradiation or high-dose cytarabine based on age.
Main Results:
- Complete remission (CR) was achieved in 91.3% of patients; 29.9% relapsed.
- Toxic death rates decreased significantly after 1990.
- Three risk groups were identified post-1990 based on white blood cell (WBC) count, hemoglobin (Hb), and lymphadenopathy, with 5-year EFS ranging from 16% to 77%.
Conclusions:
- The MCP841 protocol significantly improved CR and EFS rates compared to previous outcomes.
- Bulky extramedullary disease emerged as a critical risk factor.
- Prognostic factors like age and WBC alone were insufficient; regional variations in factors are suggested.
Background:
In the past, treatment results in Indian children with ALL have been poor, primarily due to inadequate chemotherapy and supportive care, but perhaps reflecting differences from Western countries in the pattern of subtypes. In an attempt to improve survival, we have used a more intensive treatment protocol, MCP841, and examined prognostic factors.
Patients And Methods:
Five hundred thirty previously untreated patients < 25 years of age with ALL were entered on study at the Tata Memorial Hospital, Mumbai. Treatment consisted of three successive induction cycles, consolidation and six maintenance cycles. CNS prophylactic therapy consisted of cranial irradiation (2000 cGy) for patients above two years and high-dose cytarabine for patients less than two years. The total treatment duration was two years.
Results:
Most patients had hepatosplenomegaly (80%) and or lymphadenopathy (79%) and 21% were of T-cell immunophenotype, but very few (1.3%) had CNS disease. CR was achieved in 484 (91.3%) patients and 145 (29.9%) patients relapsed. There were 36 induction deaths and 49 remission deaths, but the toxic death rate was significantly lower after 1990. In patients treated since 1990, three risk groups could be discerned: 1) WBC < 60,000 per mm3 and no lymphadenopathy (77% event-free survival (EFS) at five years): 2) WBC < 60,000 per mm3 with lymphadenopathy (53% EFS) or, WBC > 60,000 per mm3 and Hb 6 gm/dl or above (48% EFS): and 3) WBC > 60,000 per mm3 and Hb below 6 gm dl (16% EFS). In a multivariate model, only WBC, Hb and lymphadenopathy were significantly associated with EFS (P < 0.01).
Conclusions:
The CR and EFS rates achieved represent a significant improvement over previous results at this institution. Bulky extramedullary disease was an important risk factor in this series, but age and WBC alone inadequately defined risk groups, suggesting that prognostic factors may vary in different world regions.