Recurrent Histiocytosis Evolving to Myelodendritic Leukemia.

Background: Langerhans cells histiocytosis (LCH) is a rare disorder caused by proliferation of activated Langerhans cells. Although current therapies are very effective to induce a remission, multiple recurrences are common. Patients: In 1999 a 20-year-old female was admitted in the hospital to study by amenorreha for 5 months. In the exam a tumour located in the cranial base was identified and in lung a nodular infiltration was observed in the CT scan. The histological diagnosis was eosinophilic granuloma. The clinical manifestation was characterised by hypothalamic dysfunction, pituitary failure and diabetes insipidus (DI). Treatment: Telecobaltotherapy in CNS and chemotherapy (DAL HX-83/90). After therapy CNS MRI became normal, and body computed tomography (CT) scan showed minimal residual lung disease. The patient became asymptomatic, under hormonal substitutive therapy. Three years later, the patient was asymptomatic with ECOG 0, but in her peripheral blood a 3% of blast cells was detected (hemoglobin 8.2 g/dL, WBC 3.2x10⁹/L neutrophils 3%, monocytes 8%, lymphocytes 86%, blasts 3%, platelets 213x10⁹/L). Bone marrow: 0.5% blasts: CD45+, CD117+, CD33+, CD13+ weak, CD64++, CD15++, CD3−, CD2−, CD7−, CD79a−, CD19−, MPO−, CD34−, CD56++, HLADR+++, CD36+, CD11b−, CD7.1−/+lisozime+, CD1−/+, CD14 and 77.5% of cells with the same immunophenotype except CD117−, 7.1− and CD45−. One weak later we repeated the bone marrow exam and we found: 88.8% blasts cells with immunophemotype similar to blast as first exam. FISH: 88% translocation in 11q23. CT scan showed small and few nodules in lung and skin lesions were absent. She was diagnosed of leukemia involving progenitors of dendritic Langerhans’/monocytic differentiation cells: FAB AML-M0/M4. The patient has not sibling and she is receiving treatment with 2-Chlorodeoxyadenosine (0.12 mg/kg, days 1–5/28 x 6 courses) associated to epoetin-a. After two courses the patient had normalized her pheripheral blood (hemoglobin 12.5 g/dL, WBC 6.7x10⁹/L with normal distribution and platelets 485 x10⁹/L. The tolerance to therapy was excelent without adverse effects and she has a normal quality of life. Comments: The use of 2-Chlorodeoxyadenosine in LCH is based in its antiproliferative and immunomodulatory effects. CDA has been used in LCH with good results and minimal toxicity. Some cases published have showed a durable complete response in patients with LCH in skin, gastrointestinal, lungs, bone, diabetes insipidus and parenchymal CNS. In our knowledge, it has not been described previously a case of DMCL treated succesfully with CDA. Further studies are needed to determine the role of CDA in this disease, the optimal and schedule of therapy, but we have proved it may be effective even in high-risk patients with LCH. More therapies based on the pathogenesis of LCH are needed to investigate. This study has been supported by a grant from FEHHA