Case report:
An 11-year-old boy, diagnosed to have XP at the age of 6 months, was referred to us with history of fever for 10 days, vomiting and decreased appetite for 5 days. There was no history of bone pains/ bleeding manifestations. Initially he was treated with ayurvedic medications and due to non-improvement, a blood test was done which revealed severe anaemia and thrombocytopenia. Child received packed red cell and platelet transfusions at a nearby tertiary care centre, underwent bone marrow studies, and was referred to our centre with a diagnosis of acute leukaemia for further management.
On physical examination, he had multiple diffuse hyperpigmented macules all over the body with sparing of palms and soles (Figure 1). There was conjunctival congestion with bilateral pterygium (Figure 1) and mild photophobia. There was no pallor, icterus, cyanosis, clubbing, lymphadenopathy or bleeding manifestations. Liver was not enlarged, spleen was palpable 2 cm below right costal margin and testes were normal. The rest of systemic examination was normal.
Blood investigations revealed Haemoglobin: 9.9 gm%, Total leucocyte count: 1100/mm3, Platelets: 14,000/mm3. Differential Count: neutrophils 31.3%, Lymphocytes: 66.8%, Eosinophils: 0.2%, Monocytes: 1.2%, Basophils 0.5%. Uric acid: 3.8 mg/dl. Renal and liver function tests were normal. There was no biochemical evidence of tumour lysis syndrome.
Peripheral blood smear showed pancytopenia with 6% immature cells/blasts. Chest X ray was normal. Bone marrow aspiration showed 60% blasts, which were myeloperoxidase negative (Figure 2) and bone marrow flow cytometry was suggestive of B- Lymphoblastic Leukaemia (CD 5+, CD 10+, CD 19+, CD 20+, cyCD79a+, CD 33 dim positive, CD 34 -, HLA DR +). Cerebro spinal fluid (CSF) study was normal.
Child was treated using Modified BFM (Berlin-Frankfurt-Münster) ALL Protocol. Induction phase included prednisolone, vincristine, daunorubicin, L- Asparaginase and intrathecal methotrexate. He tolerated induction chemotherapy fairly well. He had good prednisolone response on day 8 of steroids with no blasts in the peripheral blood. He had hyperbilirubinemia and transaminitis after day 15 vincristine [S. Bilirubin:1.9 mg/dl (grade 2 CTCAE), SGPT: 248 U/L (grade 2 CTCAE), SGOT: 105 U/L (Grade 1 CTCAE)] during induction chemotherapy, which had improved spontaneously. Hence subsequent Day 22 and Day 29 vincristine were administered at 50 % dose, which he tolerated well without development of further hyperbilirubinemia and transaminitis. Post induction chemotherapy, his bone marrow was in remission. Subsequently, child completed Phase 1B with Cyclophosphamide, 6- Mercaptopurine and Cytosine Arabinoside along with intrathecal methotrexate without any complications. Child subsequently completed interim maintenance with 6- Mercaptopurine and Methotrexate without any toxicities. Child then received protocol M with high dose methotrexate (3 grams/m2 for cycles 1 and 2 and 5 gram/m2 for 3 and 4 cycles). He developed grade 2 mucositis after cycle 2. He also developed blood stream infection with Pseudomonas aeruginosa during cycle 3 of protocol M and was treated successfully with Cefoperazone- Sulbactam. Child completed re-intensification phase uneventfully. He is now on maintenance chemotherapy. After six cycles of maintenance, he developed hyperbilirubinemia (S. Bilirubin 2 mg/dL, Grade 2 CTCAE), for which Vincristine dose was reduced by 50%. He did not have any episodes of neutropenia during maintenance.