Intermediate-dose busulfan and cyclophosphamide as a conditioning regimen for bone marrow transplantation in a case of Fanconi anemia in myelodysplastic transformation

Abstract

Summary:tation in a patient with myelodysplastic transformation of FA, using modified conditioning with 'intermediate' dose BU and CY. We report an 11-year old female with myelodysplastic (refractory anemia with excess of blasts) presentation of Fanconi anemia. After failure of initial chemotherapy with low doses of 6-mercaptopurine and prednisolone Case report she underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched sibling. BusulfanAn 11-year-old Caucasian girl of Ouzbeck origin was referred to our institute in November 1994 with a 9 month 8 mg/kg and cyclophosphamide 40 mg/kg were used as conditioning. The post-transplant course was uneventful history of fever and anemia requiring several red cell transfusions. She was the seventh child of eight siblings. Her with fast trilineage engraftment and mild cutaneous acute GVHD. She is alive 17 months after BMT with full parents were second cousins. Two of her older sisters died of aplastic anemia. On admission, physical examination hematological reconstitution without evidence of MDS. Keywords: bone marrow transplantation; Fanconi aneshowed several 'café-au-lait' spots and micro-ophthalmy. Her height was 136 cm (−1.5 s.d.), weight 31 kg (−1 s.d.). mia; myelodysplastic transformationComplete blood count showed Hb 62 g/l, RBC 2.2 × 10 12 /l MCV 87 fl, WBC 1.1 × 10 9 /l with 6% granulocytes, 20% monocytes, 74% lymphocytes and 18 × 10 9 /l platelets. Fanconi anemia (FA) is a rare autosomal recessive disease, Bone marrow aspiration from two sites (sternum and poscharacterized by developmental malformations, bone marterior iliac crest) revealed markedly reduced cellularity with row hypoplasia 1 and frequent development of clonal hemo-9-20% blast cells, 30% myeloid cells, 20% monocytes, poietic abnormalities -myelodysplasias and nonlympho-23% erythroid cells, and 10% lymphocytes, respectively. cytic leukemias.2,3 The treatment of choice for bone Morphologically, the blast cells appeared to be monoblasts. marrow failure in FA is allogeneic bone marrow transplanCells of the myeloid line showed unequivocal dysplastic tation from an HLA-compatible sibling. One of the most features: hypogranularity, nuclear hypersegmentation, successful conditioning regimen combines low-dose cyclocellular gigantism, cytoplasmic vacuolation. Megaphosphamide (CY) and low-dose thoracoabdominal karyocytes were present in sufficient numbers, but were irradiation (TAI) and leads to approximately 75% long-term severely dyspoietic with mononuclear and microforms. survival rate.4 However, for patients with FA, developing Dyserythropoiesis was not present. On trephine biopsy, leukemic or myelodysplastic transformation, results of bone cellularity of the bone marrow was decreased to 5-30% marrow transplantation are much less encouraging with less in different areas with predominance of lymphocytes and than half of patients surviving.5 Preparative regimens for monocytes, reduction of both myeloid and erythroid linthese conditions have included conventional dose TBI and eages, and cl...

Fludarabine‐based stem cell transplantation protocol for Fanconi's anaemia in myelodysplastic transformation

“…Furthermore, Socie et al (1998) have reported on the long‐term follow‐up of 50 FA patients, and concerns related to high incidence of epidermoid carcinoma in this cohort have led to the discontinuation of irradiation within the conditioning regime, although Flowers et al (1996) have demonstrated that even without irradiation transplanted FA patients had a higher than expected incidence of cancer. Therefore, even for FA patients with severe aplastic anaemia who have sibling donors, there is no ideal conditioning protocol, and experience with SCT in patients with myelodysplastic transformation of FA is even more limited (Maschan et al , 1997).…”

Allogeneic stem cell transplantation in patients with Fanconi's anemia and myelodysplasia or leukemia utilizing low-dose cyclophosphamide and total body irradiation

“…Other case reports corroborate that allogeneic SCT may be curative in FA patients who present with myelodysplasia or leukemia. [9][10][11] As noted from the review of the literature, no uniform regimen has been used in the different reported patients.…”

Anemia de Fanconi: Consideraciones actuales

“…La existencia de malformaciones extensas se asocia con una supervivencia del 14 % frente al 44% de los que no las tienen. Los resultados de TPH en pacientes con SMD o LNLA son muy desesperanzadores 60 . Se debe intentar conseguir la remisión completa con el menor número de fármacos alquilantes y buscar regímenes de acondicionamiento diferentes.…”