L. S. Arya

INFECTIONS IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: An Analysis of 222 Febrile Neutropenic Episodes

A retrospective analysis was performed on febrile neutropenic episodes in patients with acute lymphoblastic leukemia (ALL) from 1992 to 2002. There were 222 febrile neutropenic episodes in 266 ALL patients with documented ANC < 500/mm3. Of the 222 episodes, 98 (44%) had documented focus of infection; the rest were fever without focus. There were 274 different sites of infection in the 98 episodes of documented focus of infection; pulmonary infections were the commonest site of infection (27.3%) followed by HEENT (22.9%). Of 69 bacterial isolates, gram-negative bacteria (n = 46, 67%) were twice as common as gram-positive bacteria (n = 23, 33%). Most common site of isolation for gram-negative bacteria was blood (50%) followed by urine (32.6%). Blood (78.3%) was predominant site of isolation of gram-positive bacteria followed by HEENT (8.7%). Escherichia coli (45.7%) was the commonest gram-negative isolate, while Staphylococcus aureus (39%) was the commonest gram-positive bacterial isolate. There were a total of 22 fungal isolates, the majority from urine (n = 12) and HEENT (n = 9). Of the 22 fungal isolates, 19 were detected in induction phase of chemotherapy. A total of 95/222 (42.8%) febrile neutropenic episodes improved with first-line antibiotic therapy, while modification was required in 127 episodes (57.2%). Antifungal therapy was used in 86 episodes (38.7%). There were a total of 13 deaths, 6 each during induction and intensification/consolidation phases, while 1 died during maintenance phase. Of the 13 deaths, 10 had pneumonia, 8 had bacteremia, and 7 had fungal infection. The current study stresses the importance of frequent reviewing of type, frequency, severity, and outcome of infection complications over the years to detect changing epidemiological patterns. The majority of fungal infections were detected during induction chemotherapy, which highlights the need to consider this type of infection in the evaluation of patients.

Hodgkin's disease in Indian children: Outcome with chemotherapy alone

To assess the efficacy of chemotherapy alone, using four cycles of COPP alternating with four cycles of ABVD in all stages of childhood Hodgkins disease (HD).

Pattern of relapse in childhood ALL: challenges and lessons from a uniform treatment protocol.

This retrospective analysis of 254 children less than 15 years of age treated with MCP-841 protocol from June 1992 to June 2002 was undertaken to identify the pattern of relapse and determine management lacunae. Two hundred twenty-three (87.8%) children achieved a complete remission of whom 40 (17.9%) relapsed. The mean age of relapsed patients was 6.5 years. The male/female ratio was 9:1. There were 23 (57.5%) isolated bone marrow (BM), 7 (17.5%) isolated central nervous system (CNS), 2 (5%) isolated testicular, 5 (12.5%) BM+testes and 1 each of BM+CNS, CNS+testes, and isolated bone relapses. Twenty-seven children (67.5%) relapsed on-therapy whereas 13 (32.5%) relapsed posttherapy. All 9 CNS relapses occurred on-therapy whereas 5/8 (62.5%) of testicular relapses occurred posttherapy. Lymphadenopathy was the only significant predictor for relapse. High-risk features such as age less than 1 year and greater than 10 years (P=0.047) and white cell count greater than 50.0×109/L (P=0.044) were significantly more frequent in patients with early on-therapy relapse than in patients with off-therapy relapse. The overall survival in the entire study cohort was 67±3.5%. Modest survival outcome, relapse while on chemotherapy and the higher incidence of CNS and testicular relapse indicate the need for reappraisal of our treatment protocol. There is a need of identifying risk factors and high-risk groups in our set of patients and risk-stratified intensification of chemotherapy in them.

Pattern of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in childhood acute lymphoblastic leukemia in India.

In 120 cases of acute lymphoblastic leukemia (median age 8 years), IgH chain gene was rearranged in 99% B-Cell Precursor (BCP) ALLs and 13% T-ALLs. One or the other TCR locus was rearranged not only in all T-ALLs, but also in 87% of BCP-ALLs. TCR-beta rearrangement in BCP-ALL was associated with a higher mean age at presentation (8.7 vs. 6.2 years, P=0.008), lower mean platelet counts (61.2x10(9)/l vs. 103.7x10(9)/l, P=0.003) and a poorer DFS (% cummulative survival 0 vs. 88.9+/-10.5, P=0.004). TCR-gamma rearrangement in T-ALL was associated with a higher mean WBC count (186.3x10(9)/l vs. 63. 4x10(9)/l, P=0.002). Also, the pattern of rearrangement of these genes appeared to be different from the West; viz. TCR-beta rearrangement in a higher proportion of BCP-ALLs (58%, 95% confidence intervals 45-69%), invariable deletion of Cgamma1 and only monoallelic rearrangement for TCR-delta locus. This repertoire of gene rearrangement may have a bearing on the poor treatment outcome reported previously from our geographic region.

Immunological subtypes of acute lymphoblastic leukemia in North India

Pretreatment immunologic marker analysis in 152 adult and childhood patients of ALL and ALL/lymphoma employing multiple monoclonal antibodies and hetero-antisera revealed three major subgroups, i.e. T-ALL (37.7%), N-ALL (33.1%) and C-ALL (21.5%). The early age peak was absent, males predominated in all the subgroups and T-ALL had increased incidence of thymic mass. Leucocyte counts of 50,000 X 10(6)/l were equally frequent in the three groups. T-ALL showed marked heterogeneity by showing a variety of markers such as T-helper/inducer, T-suppressor/cytotoxic, p-24, Ia and CALLA. These results show a high prevalence of unfavourable prognostic factors in ALL in our geographic region which might be related to socioeconomic and/or environmental factors.

Autoimmune hemolytic anemia complicating disseminated childhood tuberculosis.

An 8-year-old girl presented with severe autoimmune hemolytic anemia (AIHA) in association with mediastinal widening. Biopsy of mediastinal lymph node confirmed the diagnosis of tuberculosis. A diagnosis of disseminated tuberculosis in association with AIHA was made, and the patient was treated with steroids and antitubercular therapy. This is the first report case of AIHA in association with childhood tuberculosis; we also discuss other reported cases of AIHA in association with adult tuberculosis in English literature

Granular acute lymphoblastic leukemia with hypereosinophilic syndrome.

9/l), features of hypereosinophilic syndrome, and acute lymphoblastic leukemia (ALL-L2), the latter characterized by the presence of granular blasts. Blasts were negative for myeloperoxidase, non-specific esterase, acid phosphatase, periodic-acid Schiff stain, and toluidine blue. They exhibited an early pre-B immunophenotype (TdT, CD19, CD10, CD20 and CD22 positive) and stained negative for T (CD7, CD2, CD5 and CD3) and myeloid markers (MPO, CD33 and CD13). Chromosomal analysis revealed a normal karyotype. To the best of our knowledge, this case represents the first report of the coexistence of granular ALL and hypereosinophilic syndrome.

HEMATOLOGICAL RESPONSES TO HYDROXYUREA THERAPY IN MULTITRANSFUSED THALASSEMIC CHILDREN

Fifteen multi-transfused thalassemic children between 3–6 years of age (seven boys and eight girls) were administered hydroxyurea for 5 days and three such cycles were repeated at 15 days interval. Rise in hemoglobin levels was observed in 13, 8 and 7 cases, while rise in mean hemoglobin F was seen in 8, 11 and 10 cases following 1st, 2nd and 3rd course of hydroxyurea therapy respectively. Rise in hemoglobin level was associated with transient rise in fetal hemoglobin level. Though the changes in mean hemoglobin levels and hemoglobin F levels were statistically insignificant, a definite trend of rise in hemoglobin and hemoglobin F was observed.

Expression of genes implicated in multidrug resistance in acute lymphoblastic leukemia in India.

Abstract In order to investigate the phenomenon of multidrug resistance as a possible mechanism for poor response to treatment in patients with acute lymphoblastic leukemia (ALL) from India, a series of 32 cases of de novo untreated ALLs were analyzed by a cDNA-PCR approach to estimate the relative mRNA levels of the MDR-associated genes encoding MDR1, MRP, GSTπ, and GSTμ. The expression of β2 microglobulin served as an internal standard. Quantifiable transcripts were observed in 20 patients for MRP, in 5 for MDR1, in 24 for GSTπ, and in 19 for GSTμ. The values ranged from undetectable to 132% of the control A549 cell line for MRP, undetectable to 49% of the HL60/DNR control cell line for MDR1, undetectable to 268% of A549 control cell line for GSTπ, and undetectable to 247% of A549 control cell line for GSTμ mRNA. Increased MRP levels were associated with increased GSTπ and GSTμ levels (p<0.01 for both), and increased levels of MDR1 were associated with increased GSTπ levels (p<0.05). The present observations showed no correlation between the MDR1 and MRP values with treatment outcome, in terms of either achieving a complete remission or predilection to early relapse. In view of some recent studies that envisage MRP as an energy-dependent pump involved in the efflux of GSH conjugates, the simultaneous up-regulation of transcription of all these genes might well be part of an integrated detoxification response that has been switched on after exposure to an environmental stress.

Pyogenic Liver Abscesses in Children

Five children with pyogenic liver abscess were admitted to Institute of Child Health, Kabul during the period 1978 to 1980. All patients were males, and their ages ranged from 4 to 10 years. The clinical picture was characterized by fever, upper abdominal pain, enlarged tender liver with raised right dome of the dia phragm. The abscesses were located in the right lobe of liver in all cases, and they were solitary in three cases. Staphylococcus aureus was the etiologic agent in four cases and Escherichia coli in one. Open surgical drainage coupled with prompt parenteral antibiotic therapy in all cases seem to have favorably influenced the outcome. With a high index of suspicion pyogenic liver abscess in children can be diagnosed clinically without the aid of hepatic radionuclide scanning.