Background: Non-Hodgkin lymphoma is a common malignant disorder in paediatric and adolescent age group. There is a need of large-scale studies to understand the disease pattern in Pakistan as no official registry exist in most of the developing countries. This study comprised a large cohort of 223 patients, spanned over a decade from January 2008-December 2019 and aimed to report the prevalence of subtypes, demographics and immunohistochemical profile from this region. Methods: Retrospective study, conducted at Indus hospital and health network and Ziauddin university hospital, Karachi, Pakistan. Sequential data analysis was carried out on all consecutive samples including both needle and excisional biopsies of patients below 18 years of age. Morphological examination of H&E stained sections along with immunohistochemistry is performed in order to identify subtypes and immunophenotypic patterns using an extensive panel of markers. Results: Our results demonstrate 66% B-cell lymphomas while 34% T-cell lymphomas. Overall male to female ratio was 3.3:1 with median age 8 years (1.1–17 years). Among B-cell lymphoma, Burkitt lymphoma is most common while in T-cell, T-lymphoblastic lymphoma is the most common subtype. In anaplastic large cell lymphoma category, null cell phenotype was predominant, i.e., 65%. T-NHL frequency is found to be higher in our population. However, results of immunohistochemistry are similar to published literature. Conclusion: The study will help to identify disease patterns in terms of subtypes of NHL and its immunohistochemical profile that plays a vital role in diagnostic, prognostic and therapeutic implications.

Childhood acute myeloid leukemia (AML) harboring core binding factor (CBF)–associated translocations are considered as a favorable cytogenetic subgroup. The 2 major subtypes of CBF-AML include t(8;21) and inversion of chromosome 16, accounting for ∼25% of patients. Because of expensive and toxic treatment, which may require hospitalization during the entire course of induction chemotherapy, most of the centers in Pakistan neither workup for this low-risk entity nor offer curative treatment. Therefore, we adopted an approach of screening AML cases for the presence of CBF with the rationale of offering curative treatment to this subgroup. Data of 244 cases were reviewed, and translocations were found in 72 (34%) patients among them, 59 (82%) had t(8;21) and 13 (18%) showed inversion of chromosome 16. The event-free survival with and without abandonment was 36% and 40%, respectively. Among 44 patients who completed treatment, 26 (59%) are leukemia-free, while 18 (41%) relapsed. None of the relapsed patients received salvage chemotherapy or hematopoietic stem cell transplant. Treatment-related mortality and abandonment was found in 24% and 10% of patients, respectively. The frequency of CBF-AML is higher in our study; however, poor outcome demands holistic measures in supportive care to improve the survival.

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.

Objectives: Acute leukaemia is the most common and highly curable childhood malignancy; subtyping and identification of antigens via immunophenotyping helps in treatment plan as well as minimal residual disease monitoring. Methods: This retrospective study was conducted at the Haematology section of the clinical laboratories of Ziauddin University Hospital and The Indus Hospital, Karachi conducted at January 1st, 2012 to December 31st, 2017. The study included 1379 cases of de novo acute leukemia from 2012 to 2017. Among these, 80% were diagnosed by using four color flowcytometry (FACS Calibur), 9% and 11% via immunohistochemistry on bone marrow trephine biopsy samples and morphological examination respectively. Results: The mean age of patients was 7.4 ± 4.3 years while male to female ratio was 1.75:1. Lymphoblastic leukaemia accounted for 77.2% and myeloid leukaemia 21.2%. Amongst lymphoblastic lineage, B-ALL was 80.4% while T-ALL was 19.6%. Among the phenotypic expression of B-ALL, CD79a (99.8%) had the highest positivity. In B-ALL, CD13 (29.8%) was the most common aberrant myeloid marker. Aberrant expression of CD79a observed in 11.1% of T-ALL cases. In non APL AML, aberrant expression of CD79a and CD19 was observed in 6.6% and 5.5% of cases respectively. Conclusion: Overall immunophenotypic profile, expression of aberrant phenotypes and subtype distribution in our patients was similar to international literature except for a relatively high frequency of T-ALL which was discordant from the western data. doi: https://doi.org/10.12669/pjms.37.3.3552 How to cite this:Jamal S, Meraj F, Mansoor N, Parveen S, Shaikh A, Jabbar N. Distribution of subtypes and immunophenotypic characterization of 1379 cases of paediatric acute leukaemia. Pak J Med Sci. 2021;37(3):---------.  doi: https://doi.org/10.12669/pjms.37.3.3552 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 4 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. doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1721 How to cite this:Meraj F, Jabbar N, Nadeem K, Taimoor M, Mansoor N. Minimal residual disease in childhood B Lymphoblastic Leukemia and its correlation with other risk factors. Pak J Med Sci. Special Supplement ICON 2020. 2020;36(1):S20-S26.  doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1721 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.