Philadelphia chromosome-positive acute lymphoblastic leukemia with extramedullary and meningeal relapse after allogeneic hematopoietic stem cell transplantation that was successfully treated with dasatinib.

Toshinori Kondo,Kunihiko Morita,Taizo Tasaka,Rui Matsumoto,Fuminori Sano,Yoshiko Matsuhashi,Takashi Sugihara,Kana Matsumoto,Lisa Koresawa,Hideho Wada,Hirotoshi Tokunaga,Hidekazu Nakanishi

doi:10.1186/2193-1801-3-177

Abstract

Central nervous system (CNS) relapse is a critical issue while treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). A 58-year-old woman with Ph-positive ALL who relapsed after bone marrow transplantation for meningeal leukemia was treated with high-dose methotrexate, which resulted in remission. She underwent allogeneic cord blood transplantation followed by reduced intensity conditioning chemotherapy with imatinib; however, she experienced CNS relapse and developed an extramedullary mass on the right side of the temporal region. We treated 40 mg of dasatinib once daily, which had to be temporarily discontinued because she developed grade 2 pleural effusion and grade 2 hematemesis. After reinitiation of dasatinib, the extramedullary mass disappeared and meningeal leukemia ameliorated almost immediately. With 40 mg dasatinib administered once daily, its trough level and cerebrospinal fluid (CSF) concentration were 32 ng/mL and below the sensitivity threshold of 1 ng/mL, respectively. Treatment was continued, and the patient remained in complete remission until she died of pneumonia 7 years after the initial diagnosis of ALL. Dasatinib can be an effective treatment for Ph-positive ALL with CNS relapse. Although the concentration in the CSF seems low, it may be sufficient to exert anti-leukemic effects in the human CNS.

Highlights

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) is a serious hematological malignancy that usually requires combination chemotherapy to achieve complete remission
The oral tyrosine kinase inhibitors (TKIs) imatinib and dasatinib have been prescribed for the treatment of relapsed Ph-positive ALL after hematopoietic stem cell transplantation (HSCT) (Ishida et al 2010; Czyz et al 2010; Millot et al 2009; Takami et al 2006)
TKI combined with conventional chemotherapy and incorporated into the transplantation strategy has improved the longterm survival of patients with Ph-positive ALL and has allowed the de-escalation of chemotherapy

Summary

Background

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) is a serious hematological malignancy that usually requires combination chemotherapy to achieve complete remission. The patient was diagnosed with Ph-positive precursor B-cell ALL in April 2005, when imatinib-combined induction therapy was initiated (Yanada et al 2006) She exhibited complete hematological and cytogenetic responses, and bcr-abl transcripts were negative according to RT-qPCR. 3 months after BMT, she relapsed with meningeal leukemia, despite being treated with prophylactic intrathecal chemotherapy before BMT She was subsequently administered high-dose MTX therapy and 6 cycles of MTX-based intrathecal chemotherapy. This regimen eliminated lymphoblastic cells from her CSF, but 1.6 × 105 copies/μg of RNA p210 bcr-abl transcripts were still detected in her marrow blood. Imatinib and intrathecal chemotherapies were initiated again, and whole-brain irradiation (24 Gy in total) was added to her treatment regimen She achieved remission, and imatinib therapy was continued to prevent CNS relapse. Until the time of her death, no evidence of ALL recurrence was observed

Discussion and Evaluation

Findings

Conclusion