Indian Pediatrics 1999;36: 1054-1056
|Mamta Manglani, Muralidhar H.P., Abhay
Bhoyar, Rajiv Shah and M.R. Lokeshwar
From the Division of Hematology-Oncology, Department of Pediatrics, L.T.M.M.C. and L.T.M.G. Hospital, Sion, Mumbai 400 022, India.
Reprint requests: Dr. Mamta Manglani, Professor of Pediatrics
and Chief, Division of Hemato-Oncology, 51, Sea Springs, B.J. Road, Band Stand, Bandra
(W), Mumbai-400 050, India.
Bone marrow confirmed the diagnosis of acute nonlymphoblastic (myelomonocytic) leukemia (FAB-M4/M5 type) according to morphology. In view of an extremely poor prognosis despite treatment, as well as unafford-ability, the patient was not administered any specific treatment. Supportive care was conti-nued. However, he succumbed one month later.
Fanconi's anemia is a type of constitutional hypoplastic anemia, which presents with pancytopenia and certain phenotypic features including short stature, microcephaly, ano-malies of the radius, tumors, renal anomalies, etc.(2). Leukemic transformation in Fanconi's anemia has been reported in more than 60 children representing close to 10% of cases(2,4-6). Generally, children with Fanconi's anemia present at a mean age of 8 years(1). However, it has been reported that the mean age of presentation in those who developed leukemia was 10 years, with leukemia being diagnosed at a mean age of 14 years(2). The male to female ratio amongst those who developed leukemia has been documented to be 1.3: 1(2). Advances in treatment such as better supportive care and bone marrow transplantation have contributed to a prolonged survival in children with Fanconi's anemia, thereby providing more time for malignancies to occur(2,8).
Amongst the various types of leukemias reported, the commonest have been acute myeloblastic leukemia followed by acute myelomonocytic(2,4-7). This is an unusual finding in view of known frequency of acute lymphoblastic morphology in leukemia of the age range of Fanconi's Anemia patients(4). The other types of acute nonlymphoblastic leuke-mias such as acute monocytic leukemia, erythroleukemia are also known to occur. The outcome of these children who develop leukemia is dismal due to the combination of
anemia. No blood transfusions were received earlier. On examination, he had significant pallor, short stature (height-107 cm, <5th percentile), microcephaly (head circumference-45 cm, <5th percentile) with perioral hyper-pigmentation. He had no obvious congenital anomalies. A complete blood count revealed pancytopenia with a hemoglobin of 3.5 g/dl, a total white cell count of 2350/cu mm with a differential count of 2% polymorphs (ANC-47 cells/cu mm) and 98% lymphocytes and a platelet count of 30,000/cu mm. The corrected reticulocyte count was 0.5%. Bone marrow aspiration showed a hypocelluclar bone marrow with increased fat globules. Trephine biopsy confirmed the diagnosis of aplastic anemia. Sonographic evaluation of abdomen revealed a left ectopic kidney which on intravenous pyelography was confirmed to be a pelvic kidney. The rest of the ureteric system was normal. Chromosomal analysis showed a normal 46 XY karyotype with chromosomal breakages on exposure to clastogenic stress. Skeletal survey did not reveal any abnormality. In view of the clinical features and hemato-logical findings, a diagnosis of Fanconi's anemia was arrived at. The child was put on nandrolone decanoate in the dose of 2 mg/kg/week along with alternate day oral cortico-steroids, i.e., prednisolone, in the dose of 10 mg.
During the follow up, the patient's peripheral blood counts were maintained at a mean of Hb of 7.6 g/dl, ANC of 280 cells/cu mm and a platelet count of 18,000/cu mm, with no major medical events or adverse drug reactions. However, after 9 years, (1994), he presented to us with fever, epistaxis and hepatosplenomegaly. In view of organomegaly, a diagnosis of leukemic transformation was considered. A complete blood count, a bone marrow aspiration and biopsy was performed, besides other necessary investigations. Peri-pheral blood counts documented pancytopenia.
Fanconi's anemia is the best recognized constitutional aplastic anemia(1). It has an autosomal recessive inheritance pattern. It is characterized by chromosomal breakages following clastogenic stress, various physical abnormalities and most importantly pancy-topenia(2). Patients with Fanconi's anemia are at increased risk of developing leukemia (10%)(2-7), cancers (1,2,4,8) and liver disease(2,4,7,9). We report a child with Fan-coni's anemia who underwent leukemic transformation at the age of 18 years.
A 9-year-old male child presented to our institution in March 1985, with complaints of bleeding from gums spontaneously. There was no history of bleeding from any other site. No family history of bleeding was elicited. Prior to this episode, the child was apparently not exposed to any drug known to cause aplastic abnormal DNA repair, lack of marrow reserve and leukemias themselves, which are difficult to treat(2). The other malignancies which have been described are heaptocellular carcinoma and squamous cell carcinoma(4,5,8). Liver diseases mostly hepatic have been reported in 5%(2,9). Oropharyngeal, gastrointestinal, gyne-cologic, and brain cancers as well as Wilm's tumor have been documented in 5% of children with Fanconi's Anemia(2). The increased susceptibility to malignancy in Fanconi's Anemia may reflect a number of predisposing factors like spontaneous chromosomal aberra-tions, impaired ability to repair DNA crosslinks(7) and susceptibility to oncogenic virus SV 40(6-8).
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