Prognostic significance of IKZF1 gene deletions in patients with B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.

Safety and efficacy of patients with refractory B-lymphoblastic leukemia treated with anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the efficacy and side effects of anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) regimen for refractory B-lymphoblastic leukemia. Methods: 10 patients with refractory B-lymphoblastic leukemia with minimal residual disease (MRD) negative after anti-CD19 CAR-T cell treatment, then bridging to allo-HSCT from November 2017 to March 2019 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Results: ①Among 10 patients, 5 were males and 5 females, with a median age of 23.6 (10-31) years. 9 patients were diagnosed refractory acute lymphoblastic leukemia and the other one was chronic lymphoblastic leukemia. 10 patients reached MRD negative 30 days after anti-CD19 CAR-T cell. ②The donors were identical sibling (2 cases) and haploidentical family member (8 cases) . The median time from MRD negative after CAR-T treatment to transplantation were 32.5 (20-60) days. ③10 patients obtained complete haploidentical engraftment. The median time of neutrophil implantation was 15 (15-21) days, and 19 (17-30) days of platelet implantation. ④ After conditioning, no hepatic venoocclusive disease and hemorrhagic cystitis occurred. One patient had leakage syndrome and got improved after intervention such as limited water entry, albumin supplementation and diuresis. 8 (80%) patients had fever, 2 cases experienced acute graft-versus-host disease (GVHD) grade Ⅱ, 1 case with aGVHD grade Ⅲ. Among 9 survivals, localized chronic GVHD occurred in 8 patients. ⑤The median follow-up was 262 (150-540) days and the estimated 1-years overall survivaln (OS) and disease free survival (DFS) were (90.0±1.0) % and (85.7±1.3) %, respectively. Conclusion: Anti-CD19 CAR-T cell bridging to allo-HSCT regimen is a feasible choice with favorable outcome for refractory B-lymphoblastic leukemia.

Fatal neutropenic enterocolitis due to Clostridium septicum / Enterocolitis neutropénica fatal a causa de Clostridium septicum

We describe a case of Clostridium septicum enterocolitis in a patient with pre-B acute lymphoblastic leukaemia undergoing autologous stem cell transplant. In the setting of neutropenia, Clostridium septicum should be suspected in patients who develop signs and symptoms of acute abdomen.

Se describe el caso de una enterocolitis por Clostridium septicum en un paciente con leucemia linfoblástica aguda (LLA) pre-B sometido a trasplante de células madre autológico. En el marco de una neutropenia, debe sospecharse la presencia de Clostridium septicum en pacientes que desarrollan signos y síntomas de abdomen agudo.