Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia: An Analysis of Day-One Versus Day-Eight Lumbar Punctures in Remission Induction Therapy.

Introduction Traumatic lumbar puncture (TLP+) can lead to the iatrogenic infiltration of the central nervous system (CNS) by circulating leukemic blast cells in childhood acute lymphoblastic leukemia (ALL). The risk of TLP+ is increased by a number of factors at the time of presentation of the disease, such as a high white cell count (WCC), T-ALL phenotype, and unstable clinical condition of the patient. For this reason, the first lumbar puncture (LP) was deferred until Day Eight of prednisolone prophase during remission induction therapy in one set of patients. The objective was to compare the historical cohort of Day-One LP with Day-Eight LP with respect to the incidence of TLP+ and de novo CNS leukemia. Methods A retrospective comparative data analysis of 1,185 childhood ALL patients aged 1-16 years was conducted based on the electronic medical records of the pediatric hematology-oncology department of The Indus Hospital (TIH), Karachi, from January 2010 to August 2018. A total of 600 patients whose LP was done on Day One (January 2010-May 2015) were placed in cohort A, whereas 585 patients whose LP was performed on Day Eight (June 2015-August 2018) were placed in cohort B. After the examination of the cerebrospinal fluid (CSF), the status of CNS infiltration was classified as CNS-1, CNS-2, CNS-3, and TLP+. Results A total of 1,185 patients were included in the study, of whom 600 patients were in cohort A and 585 patients in cohort B. The incidence of TLP+ was found to be lower in cohort B (1.7%) as compared with the incidence in cohort A (4.3%) (p-value=0.009). However, there was an increase in the incidence of CNS-3 cases in cohort B (8%) as compared to cohort A (3%) (p-value: <0.001). When the CNS status of both the cohorts was compared with that of the internationally published data, a low incidence of TLP+ cases was noted in patients with LP on Day Eight. Conclusion The modified approach of performing the first LP on Day Eight significantly reduced the incidence of TLP+ cases. However, an unusual finding of a significant increase in the CNS-3 leukemia was noted. More prospective studies are needed to investigate this significant increase in CNS-3 cases.

Minimal residual disease in childhood B Lymphoblastic Leukemia and its correlation with other risk factors.

OBJECTIVE: To determine frequency of post induction and post consolidation minimal residual disease (MRD) in pediatric B-lymphoblastic leukemia (B-ALL) patients and its association with clinical risk factors. METHODS: This is a retrospective, cross sectional study carried out at the Indus Hospital on paediatric patients (1-17 years) was performed from May 2015 to January 2018. On day 35, MRD testing was done on bone marrow aspirate using four color flow cytometer with 0.01% cut off. Positive cases were retested at post consolidation. Data was collected for demographics, total leukocyte count (TLC), central nervous system status (CNS), Cytogenetics for BCR-ABL, MLL, TEL-AML by FISH and prophase response then analyzed in association to MRD status. RESULTS: Out of 362 patients, 133 (37%) were post induction MRD positive, with no statistically significant association to age, gender, TLC, CNS status, prophase response, BCR-ABL and TEL-AML1. However, MLL showed closely significant association (p-value=0.05). Post consolidation, 49 (44%) were MRD positive; age, National cancer institute (NCI) risk groups and CNS status showed statistical significance (p-value <0.05). CONCLUSION: Despite high frequency of MRD positivity, significant association is not observed between post induction MRD and risk factors. However, post consolidation MRD has a significant association with NCI risk groups, age and CNS status.

Prednisolone Prophase for a Week Versus Upfront Multiagent Chemotherapy in Childhood Acute Lymphoblastic Leukemia: An Analysis With Reference to Induction Mortality in a Developing Country.

In childhood acute lymphoblastic leukemia, high treatment-related mortality, especially in the induction phase of treatment, is a major challenge for developing countries. The reasons are multifactorial, including a late presentation with higher disease burden, malnourishment, and limited support services. These factors may aggravate the toxic effects of upfront multiagent chemotherapy in terms of severe neutropenic sepsis and tumor lysis. Therefore, instead of upfront chemotherapy, we offered prednisolone prophase for 1 week with the objective of balancing the antileukemic versus the toxic effect of treatment. The data of 538 patients who received induction with this approach (cohort B) are compared for induction mortality with previous records of 438 patients (cohort A) treated with upfront chemotherapy. In the presence of similar clinical characteristics including age, sex, risk group, and phenotype in both cohorts, a significant difference was found in overall induction mortality of 9% in cohort B versus 14% in cohort A (P<0.05). This difference was also significant in the high-risk and T-cell phenotype, which strengthens our hypothesis that patients with higher burden of disease may experience more fatal toxic effects with upfront intensive chemotherapy. Therefore, we suggest that the prednisolone prophase approach is beneficial to control the disease with less severe toxic effects in our settings.