Presence of minimal residual disease (MRD) following induction chemotherapy is a well-recognized risk factor to predict relapse in acute lymphoblastic leukemia (ALL). There is paucity of data on MRD and outcome in ALL from India. We share our experience in establishing a flow cytometry-based MRD assay for ALL with emphasis on determination of the number of patients who had MRD on day 35 of induction therapy and its correlation with outcome and other prognostic factors. We prospectively studied MRD in patients with ALL less than 25 years who achieved morphological complete remission with induction therapy. The initial series consisted of 104 patients with ALL. Ninety-two patients had bone marrow samples collected on day 35 of remission induction chemotherapy that was adequate for MRD. Strategy of monitoring MRD was based on flow cytometry using six color staining according the leukemia associated immunophenotype found at diagnosis. Data analysis was done using Fisher exact test. The median age was 8.5 years (range 0.9-22 years). Thirty-seven out of ninety-two patients (40.2%) had MRD at end of induction. MRD on day 35 was between 0.01 and 0.1% in 18.9% of patients, between 0.1 and 1% in 59.5% and more than 1% in 21.6% patients. Among the patients who had MRD, 16.7% had favourable cytogenetics, 60% had intermediate and 13.3% had high-risk cytogenetics. The presence or absence of residual leukemia by flow cytometry at day 35 was not significantly related to age (p = 1.0), male gender (p = 0.08) hyperleukocytosis (p = 0.25) or day 8 blast clearance (p = 0.21). However, T cell phenotype (p \ 0.001) was significantly associated with MRD. The 5-year event free survival (EFS) for patients who had MRD versus those who did not was 69% and 61.1% respectively (p = 0.41). The 5-year overall survival (OS) for patients who had MRD versus those who did not was 72.5% and 61.1% respectively (p = 0.33). Flow cytometric techniques can be applied to monitor MRD in patients of ALL undergoing induction therapy. Our results suggest MRD correlates with certain known prognostic factors. Though the EFS and OS was lower in MRD positive patients, the results were not statistically significant probably because of the small sample size.
Infantile disseminated BCG-osis is an uncommon complication of BCG vaccination and the presence of haemophagocytic lymphohistiocytosis (HLH) further complicates the clinical course due to its fatal outcome. Here, we describe a rare case of disseminated BCG-osis with HLH in a 3-month-old male child and the unusual morphological findings in the peripheral blood with its haematology analyser-based expression. The child presented with fever, failure to thrive, hepatosplenomegaly, erythematous skin rashes, and left axillary lymphadenopathy with history of BCG vaccination at birth. He was the first born of seconddegree consanguineous marriage with no significant family history of immunodeficiency disorders. Laboratory findings included anaemia, thrombocytopenia, hyperferritinaemia, hypertriglyceridaemia, and hypofibrinogenaemia which supported a diagnosis of HLH. The peripheral blood showed evidence of phagocytosis by neutrophils, pseudo-Chediak-Higashi-like inclusions, bluegreen inclusions, and intra-cytoplasmic vacuoles with shadowy appearance and cellular debris in the background. Acid-fast bacilli were demonstrated in the peripheral blood by Ziehl-Neelsen stain. His clinical condition gradually worsened with multi organ failure and fatality.
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