Central Nervous System Relapse in Adults with Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (HSCT) confers a poor prognosis in adult patients with acute lymphoblastic leukemia (ALL). Preventing CNS relapse after HSCT remains a therapeutic challenge, and criteria for post-HSCT CNS prophylaxis have not been addressed. In a three-center retrospective analysis, we reviewed the data for 457 adult patients with ALL who received a first allogeneic HSCT in first or second complete remission (CR). All patients received CNS prophylaxis as part of their upfront therapy for ALL, but post transplant CNS prophylaxis practice varied by institution, and was administered to 48% of the patients. Eighteen patients (4%) developed CNS relapse after HSCT (isolated CNS relapse, n=8; combined bone marrow and CNS relapse, n=10). Patients with a prior history of CNS involvement with leukemia had a significantly higher rate for CNS relapse (P=0.002), and pre transplant CNS involvement was the only risk factor for post transplant CNS relapse found in this study. We failed to find a significant effect of post-transplant CNS prophylaxis to prevent relapse after transplant. Furthermore, no benefit for post-transplant CNS prophylaxis could be detected when a sub-group analysis of patients with (p=0.10) and without prior CNS involvement (p=0.52) was performed. Finally, we couldn’t find any significant impact for intensity of the transplant conditioning regimen on CNS relapse after HSCT. In conclusion, CNS relapse is an uncommon event following HSCT for ALL in CR1 or CR2, but with higher risk among patients with CNS involvement pre transplant. Furthermore, neither the use of post-HSCT CNS prophylaxis nor the intensity of the HSCT conditioning regimen made a significant difference in the rate of post-HSCT CNS relapse.

Identification and characterization of a murine model of BCR‑ABL1+ acute B‑lymphoblastic leukemia with central nervous system metastasis

“…The use of tyrosine kinase inhibitors (TKIs) is the most effective method for suppressing BCR-ABL1 tyrosine kinase activity (4,5). However, single-agent TKI has not produced sustained responses in BCR-ABL1 + B-ALL, as this specific subtype of B-ALL is likely to develop significant involvement of the CNS, which acts as a ‘sanctuary’ site for leukemic cells to escape anticancer treatments (6–8). Therefore, understanding the molecular mechanisms of BCR-ABL1 + B-ALL associated with CNS metastasis is a critical step to improve therapeutics.…”

Low-dose cranial boost in high-risk adult acute lymphoblastic leukemia patients undergoing bone marrow transplant

“…This is consistent with a past study completed by Hamdi et al in adult ALL patients, suggesting that prior CNS disease indicates higher relapse rates and overall poorer prognosis after transplant. 16 Notably, patients in our CB cohort with CNS failure all had prior involvement, suggesting that 6 Gy may not be adequate in this population and that these patients may require treatment intensification. Extrapolating from the pediatric ALL literature, higher dose CB may be required in this setting.…”

Successful application of anti-CD19 CAR-T therapy with IL-6 knocking down to patients with central nervous system B-cell acute lymphocytic leukemia

“…Hamdi reported that the CNS relapses occurred at a median of 231 days in CNS leukemia patients after receiving allo-HSCT [ 6 ]. It is noteworthy, among 6 patients with no post-HSCT CNS therapy, the median time was 72.5 days.…”

“…The central nervous system (CNS) acute lymphocytic leukemia (ALL) accounts for more than 30% of all ALL relapses and confers a poor prognosis [ 1 , 2 ]. Since cranial or craniospinal radiotherapy (CRT) for CNS ALL has been almost abandoned due to its long-term side effects [ [3] , [4] , [5] ], performing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a good choice for treating CNS ALL due to the lower relapse rate [ 6 ]. Even in this setting, the incidence of CNS relapse is as high as 13% in patients with a history of CNS involvement before transplantation compared with the overall incidence of 4% in the entire cohort [ 6 ].…”