Indian Pediatrics 1999; 36:707-710 

Successful Bone Marrow Transplantation in an Infant with Wiskott-Aldrich Syndrome

From the Departments of Child Health * and Hematology, Christian Medical College and Hospital, Vellore, Tamilnadu, India.

Reprint requests: Dr. Mammen Chandy, Professor and Head, Department of Hematology, Christian Medical College and Hospital, Vellore 632 004, Tamilnadu, India.
Email: [email protected]  

Manuscript Received: October 26,1998; Initial review completed: November 23, 1998; Revision Accepted: January 15, 1999
 

Children Wiskott-Aldrich Syndrome (WAS) is an X-linked recessive disorder characterized by a triad of thrombocytopenia with decreased mean platelet volume, eczema, and increased susceptibility to pyogenic and opportunistic infections(1,2). Patients with WAS usually succumb to overwhelming infection or severe hemorrhage during the first decade of life. Although the prognosis has improved considerably with the availability of effective antibiotics and with splenectomy, the overall out- come remained poor till bone marrow transplant (BMT) became available as a treatment option. However, in developing countries due to nonavailability of sophisticated laboratories and established BMT units, this pro- cedure was not the treatment option for most patients till recently. Moreover, the cost of BMT is prohibitively expensive for majority of patients in developing countries. Despite these limitations, a few centers in India are now equipped to provide BMT for selected, patients. We report a case of successful BMT in an infant with WAS at our institution. To our knowledge, this is the first reported case of BMT for WAS in India.

Case Report

A two-month-old male infant was brought with a history of passage of blood and mucous in the stool and itchy, scaly lesions on the sclap since one month of age. He is the second child of nonconsanguineous parents, born at term following an uncomplicated pregnancy. His elder sibling, an eight-year-old boy, is healthy. His maternal aunt had lost three sons who had bloody diarrhea, eczema and recur- rent infections during early childhood and were diagnosed to have WAS. On examination, he was active and well hydrated. His weight was 4250 grams (birth weight was 3350 grams). His vital parameters were stable. There was no pallor, mucocutaneous bleeds or ear discharge. The scalp skin appeared dry and scaly. The liver was palpable two centimeter below the right costal margin but spleen was not palpable. Examination of other systems did not reveal any abnormality.

Investigations revealed a hemoglobin concentration of8.3 g/dl, platelet count of 22,000/ cu mm, total leukocyte count of 18,000/cu mm with a differential count of myelocytes 6%, metamyelocytes 5%, band forms 13%, neutrophils 32%, eosinophils 4%, lymphocytes 35% and monocytes 5%. The mean platelet volume was 6.9 femtolitres (normal 7.4-10.4 femtolitres). Immunoglobulin profile showed IgA 76 mg/dl, IgG 313 mg/dl and IgM 25 mg/dl. Stool and blood cultures were sterile.

The infant was diagnosed to have WAS in view of history of bloody diarrhea since infancy, thrombocytopenia with a low mean platelet volume and family history of WAS.

Parents of this patient opted to proceed with BMT, since he had a healthy HLA matched sibling. While awaiting BMT, he was given intravenous immunoglobulin (IVIG) 0.5 grams/kg once every four weeks. Following this period the diarrhea resolved, but thrombocytopenia persisted. BMT was done in January 1998, using HLA fully matched marrow of his elder brother. Conditioning was done using busulfan 20 mg/kg over four days(3,4) (from -9 to -6 day of BMT) followed by cyclophosphamide 200 mg/kg over the next four days (from -5 to -2 day of BMT). During this phase he developed Staphylococcus aureus septicemia which was treated with intravenous cloxacillin and gentamicin. All transfused blood products were irradiated and were infused using a leukocyte filter~ Bone marrow was aspirated from multiple sites from the donor under general anesthewsia. A total of 15x1Ox nucleated cells/kg. was infused intravenously. There were no immediate complications.

An absolute neutrophil count of >500 cu mm was achieved on the 15th day following BMT and an unsupported platelet count of >20,000/cu mm on the 69th post BMT day. The last red cell transfusion was given on the 57th day and platelet transfusion on the 62nd day following BMT. He had received a total of 340 ml/kg of packed red cells, 110 units of platelet rich concentrate and five units of fresh frozen plasma during the entire hospital stay.

The infant was given cyclosporin (day-4 till day 38 of BMT) and methotrexate (on day 1 and day 3 following BMT5 for prophylaxis against graft versus host disease (GVHD). He also received acyclovir and fluconazole for prophylaxis against herpes simplex, cytomegalo virus (CMV) and candida infection. He developed mild cutaneous GVHD on the 26th day following BMT, which subsided with steroid therapy. On the 38th post BMT day he developed severe hypertension with encephalopathy, hence cyclosporin was discontinued. On the 39th day following BMT he developed fever, purulent nasal discharge and appeared sick. However, blood and nasal swab cultures were sterile. He was empirically treated with vancomycin and imipenem following which he improved. Since polymerase chain reaction (PCR) for CMV on a blood sample was positive, he was given intravenous gancyclovir for five weeks. There were no other complications such as pneumonia, hemorrhagic cystitis or veno occlusive disease of the liver. Infant was discharged from hospital on the 105th day following BMT. At discharge his hemoglobin was 12 g/dl, platelet count was 76,000/cu mm, total leukocyte count was 5,000/cu mm with a differential of netrophils 20%, lymphocytes 68%, monocytes 7% and eosionophils 5%. Liver function test, serum creatinine and serum electrolytes were within normal limits. He was sent home on co-trimoxazole prophylaxis against Pneumocystis carinii infection, predniosolone and monthly IVIG. Prednisolone was tapered and stopped over four months and IVIG after 10 months. Cotri-moxazole is being continued. He was followed up monthly with complete blood count estimation. In addition, he had regular development assessment. At follow up ten months post BMT, at the age of 14 months, he was able to walk with support and say a few words. His developmental age was considered to be consistent with his chronological age. His platelet count was 2,46,000/cu mm, hemoglobin concentration was 12.5 g/dl and total leukocyte count was 20,000/cu mm with a differential of neutrophils 25%, eosinophils 3%, lymphocytes 70% and monocytes 2%. He has remained well and has not had any infections, eczema or diarrhea since BMT was done.

Discussion

BMT has been developed during the last three decades as the treatment for WAS and other lethal immunodeficiency syndromes(5,6). With HLA fully matched trans- plantation the cure rate has been 80-90%, whereas the outcome of HLA haplomatched BMT has been poor(4,7,8). To our know- ledge, this is the first successful report of BMT for an immunodeficiency disorder in India.

This patient had remarkably few transplant related complicatins. He had mild GVHD, which responded well to predni-solone. The limited nature of GVHD in patients with WAS has been observed by other authors also(9). This is probably due to the underlying immunologic abnormality and younger age of these patients. The other complication was an episode of probable sepsis, which was treated with imipenem and vancomycin. Thorough aseptic precautions in the BMT unit playa major role in controlling infections in these patients.

At ten months from the transplant, our patient is in an exceIlent clinical condition free of all complications of the disease. However, he needs close follow up with regard to his growth and development and for delayed complications of the disease and treatment. The exceIlent clinical response and reason- ably uncomplicated post transplant course of our patient suggests that an early BMT from a histocompatible donor is possible for patients with WAS in our country also. This case also demonstrates that the units in this country have the technical competence to perform BMT in a six-month-old infant weighing five kilogram. The major limiting factor is the expense of this therapy. The cost of BMT for this patient was rupees eight lakhs. However, this is one-tenth the cost of BMT in developed countries. The success with this case indicates that curative therapy for patients with fatal congenital immuodeficiency diseases, who can not otherwise be cured, is possible at a lower cost in India.

 References