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Background: Current drug therapy for myelofibrosis does not alter the natural course of the disease or prolong survival, and allogeneic stem cell transplantation is the only curative treatment modality. For over a decade, the Janus kinase (JAK) inhibitor ruxolitinib has been the standard of care. More recently, newer-generation JAK inhibitors have joined the ranks of accepted treatment options. Objectives: The primary goal of treatment is to reduce spleen size and minimize disease-related symptoms. Prognostic scoring systems are used to designate patients as being at lower or higher risk. For transplant-eligible patients, transplant is offered to those with a bridge of a JAK inhibitor; patients who are not eligible for transplant are usually offered long-term therapy with a JAK inhibitor. Limited disease-modifying activity, dose-limiting cytopenias, and other adverse effects have contributed to discontinuation of JAK inhibitor treatment. Conclusions: Novel JAK inhibitors and combination approaches are currently being explored to overcome these shortcomings. Further research will be essential to establish optimal therapeutic approaches in first-line and subsequent treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Daratumumab (DARA) plus bortezomib, thalidomide, and dexamethasone (D-VTd) represent the standard of induction care in Europe for autologous stem cell transplantation (auto-SCT)-eligible, newly diagnosed multiple myeloma (NDMM) patients. This study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after auto-SCT. Our findings indicate that patients treated with D-VTd experienced longer neutrophil and platelet engraftment times than those treated with VTd. Additionally, D-VTd treatment was associated with a higher incidence of febrile neutropenia and grade 2 or higher diarrhea. However, no significant differences were observed in the median number of days to discharge. The conclusion we can draw from our real-life study is that a four-drug induction therapy containing DARA does not impact transplant safety outcomes. Background: This real-life study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after autologous stem cell transplantation (auto-SCT). Methods: Sixty consecutive NDMM patients received four cycles of induction therapy with D-VTd. The conditioning regimen consisted of melphalan 200 mg/m2. These patients were compared with a historical control group of 80 patients who received four cycles of VTd as induction therapy. Results: The median days to reach neutrophil and platelet engraftment significantly differed between patients treated with D-VTd (11 and 13 days, respectively) and VTd (10 and 12 days). Univariate Cox analyses show that patients treated with D-VTd had a hazard ratio of neutrophil engraftment that was 42% significantly lower than those in the VTd arm (HR: 0.58, p = 0.002), and a multivariate model confirmed this result. Patients treated with D-VTd developed FN more frequently. Univariate and multivariate logistic regressions revealed an association between D-VTd and FN. Delayed engraftment did not correlate with more extended hospitalization. No patients died in the first six months after transplantation. Conclusions: Our real-life study showed that a four-drug induction therapy containing DARA does not impact transplant safety outcomes. [ABSTRACT FROM AUTHOR]

Relapsed or refractory (r/r) Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) still represent an unmet clinical need despite the new immune therapies available for these patients. We report the case of a Ph + ALL relapsed one year after allogeneic stem cell transplant. After one DLI was started CAR‐T program with brexucabtageneautoleucel, using as bridging treatment ponatinib, vincristine and prednisone. Brexu‐cel infusion was performed in 2023, without CRS or ICANS onset. One month after Brexu‐cel infusion BM aspirate and CT‐PET showed recovery of full donor chimerism, MRD negativity and complete metabolic remission. Subsequently was started maintenance with ponatinib: at last follow‐up, the patient persisted in leukemia‐free status. CAR‐T cells represent the most powerful treatment for r/r Ph + ALL but there is no consensus about the optimal bridging strategy and also regarding the management algorithm during "post CAR‐T phase". Here, we report the efficacy of ponatinib as a bridge to anti‐CD19 CAR‐T cell therapy and as post CAR‐T maintenance. Our experience suggests that a preserving approach with TKI associated to low‐dose chemotherapy can be the optimal bridging therapy prior to CAR‐T and that an "MRD‐guided" and "TKI‐based" maintenance strategy can represent the best choice for Ph + ALL which satisfactorily responds to CAR‐T. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a clinically challenging modality for the treatment of many hematologic diseases such as leukemia, lymphoma, and myeloma. Graft-versus-host disease (GVHD) is a common complication after allo-HSCT and remains a major cause of morbidity and mortality, limiting the success of a potentially curative transplant. Several microRNAs (miRNAs) have recently been shown to impact the biology of GVHD. They are molecular regulators involved in numerous processes during T-cell development, homeostasis, and activation, and contribute to the pathological function of T-cells during GvHD. Here, we review the key role of miRNAs contributing to the GvHD; their detection might be an interesting possibility in the early diagnosis and monitoring of disease [ABSTRACT FROM AUTHOR]