BUSULFAN, CYCLOPHOSPHAMIDE AND MELPHALAN AS CONDITIONING REGIMEN FOR BONE-MARROW TRANSPLANTATION IN CHILDREN WITH MYELODYSPLASTIC SYNDROMES

As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In y oung patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogenei c bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pedia tric patients with MDS received a marrow transplant from an HLA-identi cal, mixed lymphocyte culture (MLC) nonreactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB ) in two patients, RAEB in transformation (RAEB-t) in three, and juven ile chronic myelogenous leukemia (JCML, the pediatric counterpart of a dult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melp halan, three alkylating agents potentially capable of killing also dor mant preleukemic stem cells. The preparative regimen was very well tol erated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyse s have demonstrated a full chimerism of donor cells and the complete d isappearance of trisomy 8 detected before transplant in three cases. A ll surviving patients have a Karnofsky score of 100%. One boy, affecte d by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C , relapsed 11 months after BMT, evolved in AML and died from progressi ve leukemia. Another patient with RAEB died on day +95 after BMT due t o interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Part icularly noteworthy is that the three children with JCML obtained a co mplete remission and one of them is now a long-term survivor.