Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation for Adults with Relapsed and Refractory Mantle Cell Lymphoma: A Single Center Retrospective Analysis in the Rituximab Era

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A Phase I/II Clinical Trial to evaluate the efficacy of baricitinib to prevent respiratory insufficiency progression in onco-hematological patients affected with COVID19: a structured summary of a study protocol for a randomised controlled trial

Objectives: Baricitinib is supposed to have a double effect on SARS-CoV2 infection. Firstly, it reduces the inflammatory response through the inhibition of the Januse-Kinase signalling transducer and activator of transcription (JAK-STAT) pathway. Moreover, it reduces the receptor mediated viral endocytosis by AP2-associated protein kinase 1 (AAK1) inhibition. We propose the use of baricinitib to prevent the progression of the respiratory insufficiency in SARS-CoV2 pneumonia in onco-haematological patients. In this phase Ib/II study, the primary objective in the safety cohort is to describe the incidence of severe adverse events associated with baricitinib administration. The primary objective of the randomized phase (baricitinib cohort versus standard of care cohort) is to evaluate the number of patients who did not require mechanical oxygen support since start of therapy until day +14 or discharge (whichever it comes first). The secondary objectives of the study (only randomized phase of the study) are represented by the comparison between the two arms of the study in terms of mortality and toxicity at day+30. Moreover, a description of the immunological related changes between the two arms of the study will be reported. Trial design: The trial is a phase I/II study with a safety run-in cohort (phase 1) followed by an open label phase II randomized controlled trial with an experimental arm compared to a standard of care arm

Haploidentical vs. sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission

Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors

Comparison of long-term outcomes in patients with refractory/relapsed grade 1-2 follicular lymphoma (FL) after allogeneic (allo-HCT) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era

Allogeneic Hematopoietic Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A CIBMTR Analysis

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes

Dosaggio ottimo e mixing in un micro-canale

Il controllo del mixing nei micro-canali, di dimensioni nell\u2019ordine del micron, \ue8 un problema di estrema importanza in molte applicazioni scientifiche ed industriali, che vanno dalla biochimica fino alle tecnologie per l\u2019informazione. Se da un lato le tecnologie miniaturizzate hanno l\u2019indubbio vantaggio di utilizzare una ridotta quantit\ue0 di fluido, dall\u2019altro hanno dimensioni tali da inibire le instabilit\ue0 idrodinamiche, rendendo estremamente lento il processo di mixing. Due differenti approcci sono tipicamente utilizzati per indurre mixing: sistemi attivi, in cui il disturbo \ue8 generato da una forza esterna tempo-dipendente, e sistemi passivi, in cui ci si affida interamente alla diffusione molecolare e/o caotica. Il presente lavoro dimostra come, controllando l\u2019iniezione, sia possibile incrementare efficacia ed efficienza del mixing di un tracciante in un micro-canale

Recurrent Hodgkin lymphoma : toward a new definition of candidates for autologous stem cell transplant in the era of positron emission tomography scan and novel agents

Standard treatment for patients with Hodgkin lymphoma (HL) unresponsive to upfront therapy or relapsing after primary treatment (RR-HL) consists of salvage chemotherapy followed by autologous stem cell transplant (ASCT). ASCT outcomes are essentially related to two factors: disease burden at the time of transplant and comorbidity status of the patient. Positron emission tomography (PET) scan is a very sensitive diagnostic instrument to measure disease status. In fact, a negative PET status before ASCT is a well-known positive prognostic factor in patients with RR-HL. The recent introduction of the biologically targeted agent brentuximab vedotin has allowed us to treat RR-HL more efficaciously with less toxicity for the patient. Use of this new agent could help achieve a PET-negative status before ASCT in a larger percentage of patients, without severe toxicities, thereby improving ASCT outcomes. Herein we discuss the current evolving scenario of RR-HL treatment

Post-transplant cyclophosphamide, a promising anti-graft versus host disease prophylaxis : where do we stand?

Post transplant cyclophosphamide (PT/Cy) in association to other immunosuppressive agents or alone has emerged as a promising pharmacological strategy in the setting of allogeneic hematopoietic cell transplant (allo-HCT). Its safety profile and effectiveness in reducing GvHD (acute GvHD incidence comprised between 15 and 30%, chronic GvHD 20-30% in the haploidentical setting) contributed to the spreading of this technique all over the world. Areas covered: This review summarizes the use of PT/Cy in the setting of allo-HCT, both for oncological and non-malignant hematological diseases. Recent studies showed the feasibility of more intense conditioning regimens instead of the original NMAC. The use of peripheral blood stem cells instead of bone marrow as graft source (slightly increase of acute GvHD grade 2 but no differences in survival outcomes) was another significant variation to the original protocol. Later on, PT/Cy alone or in combination with other immunosuppressive agents (ATG, sirolimus, cyclosporine) were tested in the HLA-matched donor setting where lower GvHD rates are reported (acute GvHD grade 3 of 5-10% and chronic GvHD of 10-20%) Expert commentary: The best graft source and type of donor is still ongoing. Moreover, the research of the best pharmacological partner of PT/Cy remains an open question