Summary:Severe congenital neutropenia (SCN) is a hematologic condition characterized by arrested maturation of myelopoiesis at the promyelocyte stage of development. With appropriate treatment using recombinant human granulocyte-colony-stimulating factor (r-HuG-CSF), SCN patients are now surviving longer, but are at increased risk of developing myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but transplantation outcomes after malignant transformation are not well established. We report results for six patients with SCN who underwent HSCT for MDS or AML between 1997 and 2001 at two transplant centers. Two patients transplanted for MDS survived. Both of these patients were transplanted without being given induction chemotherapy. Four patients, who all received induction chemotherapy for AML prior to HSCT, died. Administering induction chemotherapy prior to HSCT resulted in significant morbidity. Rapid transplantation should be the goal for the SCN patient once the diagnosis of MDS/AML is established. SCN patients should be monitored carefully for progression to MDS in order to be treated with HSCT as soon as they have progressed and before developing AML. For SCN patients who progress to AML, HSCT should still be considered, even though the risks appear to be greater.

Summary:Relapse is the major cause of treatment failure after allogeneic transplantation of children with juvenile myelomonocytic leukemia (JMML), and the role of post-transplant immunomodulation is poorly understood. We report a 12-month-old child with JMML relapsed after unrelated marrow transplantation who received cytoreduction followed by donor lymphocyte infusion (DLI) with improvement, and after addition of interferon-alpha (IFN) achieved complete donor chimerism. He was weaned from IFN and has maintained complete remission for 19 months. This is the first published report of a patient with non-monosomy-7 JMML responding to post-transplant immunomodulation and suggests a role for DLI plus IFN in these patients. Juvenile myelomonocytic leukemia (JMML) is a rare pediatric malignancy, which presents in infancy or early childhood with myeloproliferative features and hepatosplenomegally. Monosomy-7 occurs in one-quarter of these patients, and although JMML with monosomy-7 may progress more slowly, long-term outcome is the same as non-monosomy-7 JMML (10-year overall survival 6%). 1 Hematopoietic cell transplantation has led to improved outcome, with reports of 2-to 4-year overall survival varying from 24% (NMDP) to 54% (Japanese data). 2,3 The major cause of failure is relapse, with rates as high as 58% at 2 years. 2 In spite of the well-documented efficacy of post transplant immunomodulation in other disorders, published work suggesting a graft-versus-leukemia (GVL) effect of post-transplant donor lymphocyte infusion (DLI) or intereferon in JMML is limited, and responding patients have all had monosomy-7 JMML. [4][5][6] We describe a patient who relapsed early after unrelated allogeneic bone marrow transplantation for non-monosomy-7 JMML in whom DLI induced a partial response, and the addition of interferon-alpha (IFN) likely contributed to attaining and sustaining a prolonged complete remission. This observation suggests a role for post-transplant immunotherapy approaches in non-monosomy-7 JMML. Clinical historyThe patient presented at age 6 months with hepatosplenomegally, thrombocytopenia, and GI bleeding. Initial WBC was 42.8  10 9 /l and marrow assessment showed JMML (based on the International JMML Working Group criteria). 1 Cytogenetics were normal. The patient underwent a splenectomy followed by two courses of cytoreductive chemotherapy with flu/ara-C (fludarabine 30 mg/m 2 /day  5 days and cytosine arabinoside 2 g/m 2 / day  5 days), resulting in pathologic complete remission.The patient then underwent allogeneic stem cell transplant utilizing a preparative regimen of TBI (total 1200 cGy), cyclophosphamide (60 mg/kg  2), and ATG (total 75 mg/kg). Bone marrow from a 6/6 matched unrelated donor was infused with a dose of 12  10 6 CD34 þ cells/kg. GVHD prophylaxis consisted of cyclosporin and short-course methotrexate. Stage 3 skin (overall grade II, Glucksberg) acute GVHD was noted just after engraftment, but resolved with topical therapy. Day þ 100 whole blood chimerism by VNTR analysis was 90% d...

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