A rescue approach in refractory diffuse large B-cell lymphoma with obinutuzumab-redirected cytokine-induced killer cells: a first-in-human case report.

Not available.

What is the best treatment strategy before autologous peripheral blood stem cell transplantation in POEMS syndrome?

Autologous peripheral blood stem cell transplantation (aPBSCT) provides optimal outcomes in POEMS syndrome but the definition of the best treatment before aPBSCT remains to be defined because of the rarity of the disease and the heterogeneity of published case series. We collected clinical and laboratory data of patients with POEMS syndrome undergoing aPBSCT from 1998 to 2020 in ten Italian centers. The primary endpoint of the study was to evaluate the impact of prior therapies and mobilization regimen on outcome. We divided the patients into three groups: patients who did not receive any treatment before transplant (15 patients, group A: front-line), patients pre-treated with other agents (14 patients, group B) and patients treated with cyclophosphamide as their mobilizing regimen (16 patients, group C). The three groups did not show differences in terms of demographic and clinical characteristics. All 45 patients underwent aPBSCT after a high-dose melphalan conditioning regimen, with a median follow-up of 77 months (range, 37-169 months). The responses were not statistically different between the three groups (P=0.38). Progression-free and overall survival rates at 6 years were: 70% (95% confidence interval: 55-85%) and 91% (95% confidence interval: 82-99) 65%, respectively, and did not differ between the three groups. The cumulative incidence of transplant-related mortality and relapse was 4% and 36%, respectively. In conclusion, in a relatively large number of patients with POEMS syndrome, undergoing an autologous transplant, pre-treatment and disease status at transplant did not appear to have an impact on major transplant outcomes.

Severe haemorrhagic diathesis due to acquired hypofibrinogenemia in a patient with early T-cell precursor acute lymphoblastic leukaemia/lymphoma: a case report.

The most frequent haematological malignancy associated with acquired hypo/dysfibrinogenemia is multiple myeloma. We present an unusual case of severe haemorrhagic diathesis due to acquired hypofibrinogenemia in a patient with early T-cell precursor acute lymphoblastic leukaemia/lymphoma (ETP-ALL/LBL). A 57-year-old male was admitted to the General Internal Medicine Department of Padova University Hospital for acute massive haematomas of the left lower extremity associated with macrohaematuria. Coagulation tests showed prolonged prothrombin time, activated partial thromboplastin time and thrombin time due to isolated severe hypofibrinogenemia (antigen 0.70 g/L and activity 26%). The radiological workup showed a bulky lesion located in the anterior mediastinum, and a biopsy led to the diagnosis of ETP-ALL/LBL. Fibrinogen replacement therapy failed to correct the bleeding diathesis and we were able to exclude other frequent causes of acquired hypofibrinogenemia (i.e., liver dysfunction, fibrinogen-specific antibody or drug toxicity); therefore, we hypothesised that hypofibrinogenemia might stem either from enhanced removal of fibrinogen from the circulation or consumptive coagulopathy. Notably, only after initiating a specific chemotherapy treatment did the patient start showing improvement in bleeding symptoms and achieve normal fibrinogen levels.

Rituximab and Bendamustine (BR) Compared with Rituximab, Bendamustine, and Cytarabine (R-BAC) in Previously Untreated Elderly Patients with Mantle Cell Lymphoma.

BACKGROUND: Rituximab plus bendamustine (BR), and rituximab, bendamustine, and cytarabine (R-BAC) are well-known induction therapies in elderly patients with mantle cell lymphoma (MCL), according to clinical guidelines. However, a direct comparison between the two regimens has never been performed. METHODS: In this multicentre retrospective study, we compared the outcome of patients with newly diagnosed MCL, treated with BR or R-BAC. Primary endpoint was 2-year progression-free survival (PFS). Inclusion bias was assessed using a propensity score stratified by gender, age, MCL morphology, and MIPI score. RESULTS: After adjusting by propensity score, we identified 156 patients (53 BR, 103 R-BAC) with median age of 72 (53-90). Median follow-up was 46 months (range 12-133). R-BAC was administered in a 2-day schedule or with attenuated dose in 51% of patients. Patients treated with R-BAC achieved CR in 91% of cases, as compared with 60% for BR (p < 0.0001). The 2-year PFS was 87 ± 3% and 64 ± 7% for R-BAC and BR, respectively (p = 0.001). In terms of toxicity, R-BAC was associated with significantly more pronounced grade 3-4 thrombocytopenia than BR (50% vs. 17%). CONCLUSIONS: This study indicates that R-BAC, even when administered with judiciously attenuated doses, is associated with significantly prolonged 2-year PFS than BR in elderly patients with previously untreated MCL.

Dealing With High-Risk AL Amyloidosis Patients: A Single Hematologic Center Experience.

PURPOSE: To assess the feasibility and the results of Bortezomib-based treatment of "high-risk" AL-amyloidosis patients in a hematology ward. METHODS: We report on 52 high-risk amyloidosis patients treated with first-line bortezomib-based chemotherapy. RESULTS: At day 30 from the beginning of the therapy, 23 patients (44%) achieved a hematological response (complete response plus very good partial response); 14 patients (27%) achieved a partial response; 15 patients (29%) were non-responders. After a median follow-up of 28.5 months, the survival rates were 18/23 (78%) for responders; 9/14 (64%) for partial responders and 3/15 (20%) for nonresponders with a median overall survival of 43, 24 and 11 months, respectively (log-rank test: P < .001). NHYA class I-II, NTproBNP < 6500 ng/L, the hematologic response, and the partial hematological response at day 30 independently predicted the survival. There has been no significant difference (P = .173) in survival between revised Mayo stage III and IV patients although there was a trend toward a better prognosis for Mayo stage III. A suboptimal hematological response at day 30 allowed a later organ response in 12/14 patients (85%) even without therapy change and no modification of the hematological status. CONCLUSIONS: These results show that high-risk AL-amyloidosis patients can be managed safely and effectively in a hematology ward. A partial hematologic response may herald a later better response, organ response, and can allow a subsequent second-line therapy and a good survival.

High rate of profound clonal and renal responses with daratumumab treatment in heavily pre-treated patients with light chain (AL) amyloidosis and high bone marrow plasma cell infiltrate.

Daratumumab demonstrated activity in the treatment of AL amyloidosis in two recently concluded phase II clinical trials in relapsed and refractory patients. Its role in upfront therapy is under evaluation in a phase III study. In this report we evaluated the safety and efficacy of 28-day cycles of daratumumab (single agent or combined with bortezomib or lenalidomide) in 72 previously treated patients with multiple myeloma and AL amyloidosis. Fifty (69%) were refractory to the last line of therapy. After eight infusions of daratumumab, 59 patients (82%) achieved a hematologic response, with 12 (16%) complete responses (CRs) and 30 (42%) very good partial responses (VGPRs). After 16 infusions, the quality of response improved with 22 patients (30%) achieving CR and 21 (29%) attaining VGPR. Cardiac response was observed in 11 of 37 evaluable patients (29%) and renal response in 23 of 38 patients (60%). Daratumumab is highly effective in heavily pretreated patients with relapsed/refractory AL amyloidosis and high bone marrow plasma cell burden. Renal responses, which are usually rare in this setting, were frequently observed.

Bendamustine plus rituximab is an effective first-line treatment in hairy cell leukemia variant: a report of three cases.

Hairy cell leukemia variant (HCLv) is a chronic lymphoproliferative disorder classified as a provisional entity in the 2016 WHO Classification of Lymphoid Tumors. HCLv is characterized by unfavorable prognosis, low complete remission rates and limited disease control following classical hairy cell leukemia-based regimens. In this study, we report 3 cases of elderly patients with treatment-naive, TP53 un-mutated HCLv, who were effectively treated with four cycles of bendamustine plus rituximab. The regimen was completed in all the patients with acceptable toxicity. All patients achieved a complete clinical response with no evidence of residual disease at bone marrow biopsy and flow-cytometry examination. After a median follow-up of 19 months, the 3 subjects are still in complete remission. In this work, bendamustine plus rituximab proved to be an effective and feasible first-line treatment strategy for elderly patients with TP53 un-mutated HCLv.