Mohammed Ramzan

Successful Myeloablative Matched Unrelated Donor Hematopoietic Stem Cell Transplantation in a Young Girl With GATA2 Deficiency and Emberger Syndrome

Patients with GATA2 (Emberger syndrome) deficiency needs early hematopoietic stem cell transplant (HSCT) before evolving in to myelodysplastic syndrome or acute myeloid leukemia and with time given compromised organ dysfunction leads to increase regimen-related toxicities. Most published cases have used nonmyeloablative conditioning regimens, show higher incidences of rejection and relapse rates and umbilical cord blood transplant has been reported to be suboptimal in patients with GATA2 deficiency because of longer period of engraftment leads to more infections and mortality. We report a 4.5-year-old girl with GATA2 deficiency who underwent matched unrelated donor HSCT utilizing a myeloablative conditioning regimen including intravenous busulfan (total dose of 12.8 mg/kg) and fludarabine (total dose of 160 mg/m) She tolerated the conditioning regimen and bone marrow infusion well. Her initial chimerism was mixed (90% donor), cyclosporine was gradually weaned and discontinued at day+85 and this resulted in conversion to full-donor chimerism. Bone marrow assessment 3 months post-HSCT revealed normal hematopoiesis and absence of monosomy 7. At 20 months of follow-up she had full-donor chimerism with complete reconstitution of the all hematopoietic stem cells. Myeloablative matched unrelated donor HSCT represents an effective option for cure in patients with GATA2 deficiency and Emberger syndrome.

Juvenile Myelomonocytic Leukemia in India: Cure Remains a Distant Dream!

There is paucity of outcome data regarding juvenile myelomonocytic leukemia from India. We report a series of eight children. Three had monosomy 7 and one had complex cytogenetics. One with Down’s syndrome recovered spontaneously. Three refused therapy of whom only one is alive with disease. One died post chemotherapy. Three underwent allogeneic stem cell transplant after protracted delay with funds arranged from various governmental and non-governmental organizations. Of these two died (relapse-1 and intracranial bleed-1) and one is alive and disease free. In India, it’s a milestone to reach transplant due to high cost and cure still remains a distant dream.

Recurrent anemia in an infant with pneumonia: be vigilant for uncommon presentation of cystic fibrosis

Cystic fibrosis (CF) is an autosomal recessive multisystem disorder characterized by the formation of thick, sticky mucus that can hamper our various organs.1 CF is caused by the alteration of a gene located on the long arm of chromosome7 that encodes a protein, the cystic fibrosis trans membrane conductance regulator (CFTR), which functions as a chloride channel on the apical membrane of epithelial cells.2 The disorder’s common symptomatology is due to progressive damage to the respiratory system, digestive system, exocrine pancreatic insufficiency (diarrhea and failure to thrive), though their severity varies among affected individual.3 Those infant who are not having classical clinical manifestations suggestive of CF or uncommon presentation, neonatal screening or early suspicion is helpful in detection of disease which allows prompt treatment of CF related complications, improving survival and conceptualizing the treatment strategies.4 Meconium ileus may be the first manifestation of CF in the neonatal period, occurring in approximately 20% of patients with pancreatic insufficiency.5 Though iron deficiency anemia may be present due to malabsorption in children,6 transfusion dependent severe anemia in early infancy associated with CF is not mentioned in literature. Our objective of the present publication is to report the case of an infant who had uncommon presentation of CF with recurrent anemia and pneumonia without full blown evolution of the disease despite the clinical suspicion of CF.

Hemophagocytic Lymphohistiocytosis in Infants: A Single Center Experience from India

There is paucity of outcome data for hemophagocytic lymphohistiocytosis (HLH) in infants from India, especially post stem cell transplant (SCT). We report outcome data of eight infants diagnosed with HLH. Mean age was 7.1 months (range 2–11). Mutation analysis was possible in seven patients. One patient had Griscelli syndrome. In three patients, no known mutation could be identified, while in remaining three homozygous mutations in Perforin, Munc and STX11 gene were identified. All were treated as per HLH 2004 protocol. Four died during induction phase. One patient abandoned therapy. Two underwent SCT, while one is awaiting SCT. First patient is alive and disease-free at 22 months postmatched sibling donor SCT. Second underwent unrelated double cord blood transplant, but died 5 months posttransplant due to renal failure. It is feasible to offer SCT for infants with familial HLH in the developing world although barriers like sepsis and disease refractoriness remain.

Isolated bilateral uveitis in child with hypereosinophilic syndrome.

The ocular involvement has rarely been described in hypereosinophilic syndrome (HES). We report an 8-year-old girl with HES and isolated bilateral uveitis as end-organ damage. Almost 20 months after detection of persistent asymptomatic eosinophilia, she developed complete loss of vision in right eye due to retinal detachment and decreased vision in left eye. We treated this organ-threatening condition with prednisolone and imatinib mesylate, although she was negative for FIP1L1-PDGRFA fusion gene. The vision in her left eye returned to normal. At present, the child is on alternate-day low-dose prednisolone and daily imatinib. Early recognition and aggressive treatment is essential in HES with ocular involvement to save vision. Imatinib is a useful adjuvant drug even in PDGRFA/FIP1L1-negative HES.

Sickle cell disease: is hydroxyurea the final answer?

We read with interest the recent article on efficacy of hydroxyurea (HU) in sickle cell disease (SCD) [1]. We share our experience in managing nine such patients (4 males) aged between 3 and 19 years. Seven patients were on regular HU therapy (15-20 mg/kg/d) and penicillin prophylaxis for median period of 2.8 years. All had history of repeated fever, chest infections and vasoocclusive episodes before reporting to our center. Three children (all from Africa) underwent successful hematopoietic stem cell transplant (HSCT).