Predictive value of pretransplantation molecular minimal residual disease assessment by WT1 gene expression in FLT3-positive acute myeloid leukemia

The FMS-like tyrosine kinase 3 (FLT3) mutation in acute myeloid leukemia (AML) is a negative prognostic factor and, in these cases, allogeneic stem cell transplantation (allo-SCT) can represent an important therapeutic option, especially if performed in complete remission (CR). However, it is increasingly clear that not all cytological CRs (cCRs) are the same and that minimal residual disease (MRD) before allo-SCT could have an impact on AML outcome. Unfortunately, FLT3, due its instability of expression, is still not considered a good molecular MRD marker. We analyzed the outcome of allo-SCT in a population of FLT3-positive AML patients according to molecular MRD at the pretransplantation workup, assessed by the quantitative expression evaluation of the panleukemic marker Wilms\u2019 tumor (WT1) gene. Sixty-two consecutive AML FLT3-positive patients received allo-SCT between 2005 and 2016 in our center. The median age at transplantation was 55 years. The quantitative analysis of the WT1 gene expression (bone marrow samples) was available in 54 out of 62 (87%) cases, both at diagnosis (100% overexpressing WT1 with a mean of 9747 \ub1 8064 copies) and before allo-SCT (33 WT1-negative and 21 WT1-positive cases at the pretransplantation workup). Of these cases, 33/54 (61%) were both in cCR and molecular remission (WT1-negative) at the time of transplantation, 13/54 (24%) were in cCR but not in molecular remission (WT1-positive), and 8/54 (15%) showed a cytological evidence of disease (relapsed or refractory). Both post-allo-SCT overall survival (OS) and disease-free survival (DFS) were significantly better in patients who were WT1-negative (WT1 250 copies), with a median OS and DFS not reached in the WT1-negative group and 10.2 and 5.5 months, respectively, in the WT1-positive group (OS log\u2013rank p = 0.0005; hazard ratio [HR] = 3.7, 95% confidence interval [95% CI] = 1.5\u20139; DFS log\u2013rank p = 0.0001; HR = 4.38, 95% CI = 1.9\u201310). Patients with cCR who were WT1-positive had the same negative outcome as those with a cytological evidence of disease. The relapse rate after allo-SCT was 9% (3/33) in pre-allo-SCT WT1-negative cases and 54% (7/13) in WT1-positive cases (p = 0.002). At multivariate analysis, WT1 negativity before allo-SCT and grade <2 acute graft versus host disease were the only independent prognostic factors for improved OS and DFS. These data show that pre-allo-SCT molecular MRD evaluation through WT1 expression is a powerful predictor of posttransplantation outcomes (OS, DFS, relapse rate). Patients with both cCR and a WT1-negative marker before allo-SCT have a very good outcome with very low relapse rate; conversely, patients with positive molecular MRD and refractory/relapsed patients have a negative outcome. The WT1 MRD stratification in FLT3-positive AML is a valuable tool with which to identify patients who are at high risk of relapse and that could be considered from post-allo-SCT prophylaxis with FLT3 inhibitors or other strategies (donor lymphocyte infusion, tapering of immunosuppression, azacitidine). \ua9 2017 ISEH - International Society for Experimental Hematolog

Abdominal abscess and Hafnia alvei septicemia occurring during the aplastic phase after autologous stem-cell transplantation in a patient with diffuse large B-cell lymphoma.

Hafnia alvei is a motile gram-negative bacterium that is rarely isolated from human specimens, but that sometimes can be found as part of the gastrointestinal flora. Here we report a rare case of Hafnia alvei septicemia with an abdominal abscess in a 60-year-old woman with diffuse large B-cell lymphoma involving the spleen, liver, and then lymph nodes. She initially received a splenectomy, and, over a 2-year period, four courses of chemotherapy. After achieving complete remission status, she underwent autologous peripheral blood stem-cell transplantation (PBSCT). During the aplastic phase following transplantation, the patient developed fever, diarrhea, and abdominal pain, with blood cultures positive for Hafnia alvei and an abscess in the splenic recess. Considering the high surgical risk, the infection was treated, successfully, with antibiotics (imipenem/cilastatin), without surgery or computed tomography (CT)-guided percutaneous drainage. Infections due to Hafnia alvei are rare, and this is the first reported case of Hafnia alvei septicemia in an adult hematologic patient undergoing a stem-cell transplantation procedure

Fusobacterium nucleatum: a rare cause of bacteremia in neutropenic patients with leukemia and lymphoma.

Although anaerobic bacteremias are uncommon in oncohematologic patients, nevertheless they have been considered an emergent problem in the last few years. Fusobacterium nucleatum is an anaerobic Gram-negative bacillus commonly present in the oral cavity and in the respiratory and genito-urinary tracts. Over a 10-year period 18 episodes of F. nucleatum bacteremia in patients with hematological malignances (15 leukemias and 3 lymphomas) have been observed in our Department of Hematology. Predisposing factors included oropharyngeal mucositis and severe neutropenia owing to intensive chemotherapy. In our experience no septic shock occurred and the outcome of bacteremias caused by F. nucleatum was favorable

Early chemosensitivity to VAD regimen predicts a favorable outcome after autologous stem cell transplantation in multiple myeloma

We report that early chemosensitivity, defined by a greater than 50% reduction of M-component and plasma-cell marrow infiltration, after 2 cycles of VAD was correlated with a favorable outcome following autologous stem cell transplantation in 46 patients with newly diagnosed multiple myeloma submitted to high-dose therapy

Early chemosensitivity to VAD regimen predicts a favorable outcome after autologous stem cell transplantation in multiple myeloma.

We report that early chemosensitivity, defined by a greater than 50% reduction of M-component and plasma-cell marrow infiltration, after 2 cycles of VAD was correlated with a favorable outcome following autologous stem cell transplantation in 46 patients with newly diagnosed multiple myeloma submitted to high-dose therapy