Chronic myelogenous leukemia presenting with central nervous system infiltration, successfully treated with central nervous system-directed chemotherapy followed by allogeneic stem cell transplantation.

With the introduction of tyrosine kinase inhibitors (TKIs), prognosis of chronic myelogenous leukemia (CML) has improved dramatically. However, treatment for blast phase (BP) CML remains a challenge. CML infiltration of the central nervous system (CNS) is particularly rare and no effective treatment strategy has been established. The present case reports a 30-year-old man presenting with sensory deafness. Marked leukocytosis with p210 BCR-ABL1 mRNA positivity and Philadelphia chromosome detected by bone marrow biopsy confirmed the diagnosis of CML. Dura thickening in brain MRI and immature cells with Philadelphia chromosome in spinal fluid confirmed CNS invasion of CML and he was diagnosed with BP-CML. Two cycles of hyper-CVAD/MA (cyclophosphamide, vincristine, doxorubicin and dexamethasone/ high-dose methotrexate and cytarabine) therapy with dasatinib and concomitant intrathecal chemotherapy induced complete cytogenetic response and remission of CNS involvement. Bone marrow transplantation from an unrelated HLA-mismatched donor was performed and complete molecular response in bone marrow and complete remission in CNS disease was achieved. To our knowledge, this the first report of BP-CML with CNS infiltration at initial diagnosis, and shows that CNS-directed chemotherapy with dasatinib followed by allogeneic hematopoietic stem cell transplantation is useful in the treatment for BP-CML with CNS invasion in the TKI era.

[Successful treatment with low-dose etoposide for hemophagocytic syndrome following reduced-intensity conditioning for cord blood transplantation in a patient with acute myelgenous leukemia].

A 56-year-old man was diagnosed with acute myeloid leukemia with myelodysplasia-related changes. Chromosomal analysis showed a complex karyotype. Complete remission could not be achieved even after several induction chemotherapy regimens, and the patient suffered from invasive pulmonary aspergillosis. He was transferred to our hospital and underwent reduced-intensity conditioning cord blood transplantation (RIC-CBT) in a non-remission state. The conditioning regimen involved fludarabine 125 mg/m2 combined with melphalan 140 mg/m2 and total body irradiation (4 Gy). GVHD prophylaxis was tacrolimus alone at relatively low concentrations (app. 5 ng/ml). On days 6 and 9 after CBT, he experienced a pre-engraftment immune reaction and hemophagocytic syndrome (HPS). We started steroid pulse therapy, but this failed to resolve the symptoms. We then administered low-dose etoposide (50 mg/m2). The symptoms gradually resolved after three administrations of etoposide and engraftment was achieved on day 35. Satisfactory hematological recovery was noted on day 300 after CBT and the patient has maintained complete remission to date. HPS is one of the most serious complications following CBT and often results in engraftment failure. This case suggests that repeated administration of etoposide may safely and effectively overcome this serious complication in some cases.