Treatment of adult ALL with central nervous system involvement at diagnosis using autologous and allogeneic transplantation: a study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Abstract

To assess the role of hematopoietic SCT (HSCT) in adult ALL patients with central nervous system involvement at diagnosis, we retrospectively analyzed 90 patients who underwent autologous HSCT (auto-HSCT group; n ¼ 27) or allogeneic HSCT (allo-HSCT group; n ¼ 63) and reported to the Socié té Franc¸aise de Greffe de Moelle et de Thé rapie Cellulaire registry between 1994 and 2008. At the time of transplantation, 67 patients (74%) were in first CR, 15 (17%) in CRX2 and 8 (9%) with progressive disease. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 52% and 46% for the allo-HSCT and 37% and 33% for the auto-HSCT groups, respectively (P ¼ NS). The TRM at 5 years was 29.8% for the allo-HSCT group and 3.7% for the auto-HSCT group. Using univariate analysis, a time for transplantation of o12 months, the remission status at transplantation, the use of high-dose TBI and the number of the transplant were all determined to be prognostic factors for improved DFS and OS probabilities.Using multivariate analysis, we demonstrated that both the use of high-dose TBI and the remission status had a favorable impact on OS. Although the DFS and OS were better in the allo-HSCT group, the differences were not statistically significant.

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front‐line with paediatric‐inspired regimens: A retrospective multicentre Campus ALL study

“…In our study, as well as in others, 18,49 HSCT represented the most effective therapeutic option with a significant OS benefit compared to patients who relapsed after a previous transplant or who could never undergo a transplant ( p = 0.012). Even if HSCT represents the treatment of choice for VHR patients, in this series it was performed as part of the initial treatment programme only in 18 patients (25.3%) and after a relatively long median time from diagnosis (8 months, range 3–24), despite the fact that 59.2% of the entire cohort was classified as VHR.…”

“…Notably, all six Phlike ALL patients had received previous immunotherapy and one of them had a CNS relapse also after CAR-T-cell therapy, suggesting a neurotropism of this subtype; noteworthy, the combination of ruxolitinib with chemotherapy resulted in a molecular remission in a high-risk Ph-like refractory patient with a macroscopic CSF involvement. 48 In our study, as well as in others, 18,49 HSCT represented the most effective therapeutic option with a significant OS benefit compared to patients who relapsed after a previous transplant or who could never undergo a transplant (p = 0.012). Even if HSCT represents the treatment of choice for VHR patients, in this series it was performed as part of the initial treatment programme only in 18 patients (25.3%) and after a relatively long median time from diagnosis (8 months, range 3-24), despite the fact that 59.2% of the entire cohort was classified as VHR.…”

Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy

“…The approach to patients with CNS disease and the role for CNS-directed prophylaxis are areas of uncertainty. For patients with CNS disease at diagnosis, a French registry study reported that high-dose TBI and remission status had favorable impacts on OS, regardless of whether the patients underwent auto-HCT or allo-HCT [57]. A single-center analysis showed that patients with a pretransplantation history of CNS involvement were at increased risk for post-transplantation CNS relapse, inferior EFS, and worse OS.…”

Impact of central nervous system involvement in adult patients with Philadelphia-negative acute lymphoblastic leukemia: a GRAALL-2005 study

“…6 Moreover, the rate of CNS relapse remained high after allogeneic SCT, including TBI or TBI-free conditioning regimens, in patients with previous CNS involvement. [28][29][30][31] Although the number of patients is limited, this questions allogeneic SCT as being the most efficient way to reduce relapse in patients with CNS disease at diagnosis as it might for patients with other high-risk features such as MRD. 16 The inferior outcome in our patients with initial CNS disease was more likely due to toxicity since higher mortality in remission was observed in patients who received hyper fractionated cyclophosphamide and/or proceeded to allogeneic SCT.…”