Successful ibrutinib treatment for central nervous system relapse of chronic lymphocytic leukemia after allogeneic hematopoietic stem cell transplantation

Abstract

Dear Editor It is generally difficult to treat chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, ibrutinib has recently been reported to be an effective option even in such cases [1, 2]. In addition, ibrutinib has also been reported to be an effective treatment for central nervous system involvement (CNSi) of CLL/SLL [3]. We herein report a CLL/SLL patient who relapsed with CNSi approximately 10 years after receiving allo-HSCT and was successfully treated with ibrutinib. A 20-year-old Japanese man was diagnosed with CLL/ SLL in November 2009. At diagnosis, he presented with bilateral cervical lymphadenopathies that had been apparent for several months. Lymph-node biopsy showed hyperplasia of smallto medium-sized atypical lymphocytes expressing CD5, CD20 and CD23. Cells with the same phenotype were also detected in bone marrow (BM). Because he had B symptoms, he was treated with fludarabine alone followed by fludarabine, cyclophosphamide, and rituximab. Although no histological evidence was obtained, transformation was suspected based on elevated LDH and progressive lymph-node enlargement. He then received high-intensity multi-agent chemotherapy with rituximab [4, 5], but he did not achieve a durable response. Therefore, he received allogeneic bone marrow transplantation from a human leukocyte antigen-matched unrelated donor with myeloablative conditioning consisting of 12 Gy of total body irradiation and cyclophosphamide in October 2011. After HSCT, he achieved a complete response (CR), which was confirmed by whole-body computed tomography (CT) and BM examination. He was regularly followed up, and CR was last confirmed in October 2016. In January 2021, approximately 10 years after achieving the first CR, he complained of back pain and bilateral lower extremities numbness followed by gait disturbance and bladder and bowel dysfunction. Spinal magnetic resonance imaging (MRI) revealed a soft tissue mass at the level of Th4-7 infiltrating the spinal canal (Fig. 1a). Other lesions were not detected by whole-body CT, head MRI, or BM examination. Cerebrospinal fluid analysis showed elevated protein without no abnormal cells. Biopsy of the thoracic spine mass revealed proliferation of smallto middle-sized mononuclear cells expressing CD5, CD20, and CD23, based on which he was diagnosed with relapse of CLL/SLL. The patient was treated with short-course dexamethasone 20 mg/day followed by ibrutinib 420 mg/day [6]. A significant clinical response was observed after the initiation of treatment. Bladder and bowel dysfunction was resolved immediately, and he was able to walk one month later. A significant decrease in the size of the thoracic spine mass was confirmed by MRI two months after ibrutinib initiation (Fig. 1b). To our best knowledge, this is the first case in which ibrutinib was effective as salvage therapy in a CLL/SLL patient who had CNSi after allo-HSCT. There are no established standard treatments for either CNSi or relapse after alloHSCT in CLL/SLL [7, 8]. Ibrutinib has been suggested not only to be effective for CNSi but also to enhance the graft-versus-leukemia effect [3, 9], and is thus considered a reasonable treatment option in a post-HSCT setting. Additional evidence must be accumulated to clarify the efficacy of ibrutinib in this setting. * Masatoshi Sakurai [email protected]