Background: Proteasome inhibitors (PIs) represent one of the most effective classes of therapy for patients with multiple myeloma (MM) and are incorporated in many of the current treatment regimens. The first-generation PI, bortezomib, has shown impressive results in patients with either newly diagnosed or relapsed/refractory MM, but once patients become resistant, treatment is increasingly challenging. Although the existing data show that the second-generation PI, carfilzomib, is highly efficient, there is still limited knowledge regarding the response to carfilzomib-based therapy in bortezomib-resistant patients. The aim of this study was to evaluate carfilzomib treatment performance in bortezomib-sensitive versus -refractory patients, in a real-life eastern European country setting. Methods: We retrospectively evaluated 127 adult patients exposed to bortezomib with relapsed or refractory MM, that subsequently received a carfilzomib-based therapy. We investigated the differences in the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) after carfilzomib-based therapy between the two patient groups. Results: The ORR in the bortezomib-sensitive group was significantly higher than that in the refractory group, leading to a superior PFS in this category of patients. For patients presenting with a high cytogenetic risk, we observed a significant difference in PFS between the bortezomib-sensitive and -refractory group, while standard cytogenetic risk patients presented a similar PFS regardless of the bortezomib sensitivity status. In addition, in patients with ISS (International Staging System) stage I or II, the previous sensitivity to bortezomib correlated with an improved PFS, while for patients with ISS stage III, both groups had a comparable PFS. No significant differences in OS were observed between the two groups. Conclusions: In countries where novel or experimental therapies are not readily available, carfilzomib-based therapy can still be a viable therapy option for patients presenting with bortezomib-refractory status, an ISS stage III, and standard cytogenetic risk.

Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin’s lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions—Crohn’s disease, vitiligo, type I diabetes, and minimal change disease—undergoing BV therapy for Hodgkin’s lymphoma. The patients were treated with A-AVD instead of ABVD due to advanced-stage disease with high IPI scores. Results: Our findings reveal the surprising and complex interplay between BV exposure and autoimmune manifestations, highlighting the need for multidisciplinary collaboration in patient management. Notably, the exacerbation of autoimmune symptoms was observed in the first three cases where T-cell-mediated autoimmunity predominated. Additionally, BV exposure precipitated autoimmune thrombocytopenia in the vitiligo patient, underscoring the profound disruptions in immune regulation. Conversely, in the minimal change disease case, a disease characterized by a blend of B- and T-cell-mediated immunity, the outcome was favorable. Conclusions: This paper underscores the critical importance of vigilance toward autoimmune flare-ups induced by BV in patients with concurrent autoimmune conditions, offering insights for tailored patient care.

The treatment paradigm of multiple myeloma (MM) has shifted in the past years, as continuous therapy is becoming the standard of care for both newly diagnosed and relapsed patients. Although it is indisputable that continuous therapy has added a great benefit on the progression-free as well as overall survival, it is still unclear what the patients’ perspective is on this therapeutic approach. Methods: This study included 155 adult MM patients from Fundeni Clinical Institute in Romania, receiving continuous therapy with daratumumab, proteasome inhibitors, immunomodulators, or bi-specific antibodies. The patients had varied economic, social, and educational backgrounds. We developed a questionnaire to interrogate the quantitative and qualitative effect of the therapy on the patients’ personal and professional life and to identify the side effects that had the strongest impact on their quality of life. Results: 74.83% of the patients reported that the treatment they received negatively impacted their quality of life. Among them, 40% considered that the most detrimental aspects of the therapy are the financial burden and the negative impact on their professional life. One-third of the patients reported that the therapy negatively impacted their personal life and that it had a deleterious effect on their relationship with their partner and family members. In terms of the side effects experienced, patients considered that tiredness was the main factor causing a decrease in their quality of life, followed by insomnia and bone pain. Despite this, almost none of the patients considered dropping the therapy, and almost half of the patients considered that the frequent visits to the hospital offered them psychological comfort. In addition, more than 70% of the patients declared that they were afraid to stop the therapy if given the choice, with the main concerns being the fear of an early relapse. Conclusions: Although continuous therapy is associated with a high financial burden and a negative impact on both professional and personal life, the frequent visits to the hospital appear to be reassuring. Moreover, the patients would not opt for treatment discontinuation and felt safer when monitored frequently.

Recently, Brentuximab Vedotin (BV) has emerged as an important therapy not only for Hodgkin’s Lymphoma, but also for CD30-positive T cell lymphomas. Although anemia and thrombocytopenia are common myelosuppressive side effects, to our knowledge, this is the first described case of Evans Syndrome associated with BV therapy. We present the case of a 64-year-old female, diagnosed with relapsed Peripheral T Cell Lymphoma Not Otherwise Specified (PTCL-NOS), who, after receiving six cycles of BV, developed authentic severe autoimmune hemolytic anemia with strong positive direct anti-globulin (Coombs) test, simultaneously associated with severe immune thrombocytopenia. The patient was unresponsive to systemic corticotherapy, but fully recovered after a course of IV immunoglobulin.

What followed over the next decades was not merely technical refinement, but a gradual reframing of the therapy's fundamental purpose, as an immunologic treatment rather than a simple hematopoietic rescue. Long before "cellular therapy" entered the lexicon, the experience showed that most durable remissions after transplant could not be explained by cytotoxic intensification but rather by the immunologic interaction between donor and host. The donor lymphocyte infusion was the clearest conceptual breakthrough: disease relapse could be re-treated not with chemotherapy, but by intensifying the immune component alone.DLI was therefore more than a salvage strategy; it was the first prototype of adoptive cellular therapy, and engineered immunity through CAR-T cells represented the logical maturation of the this therapeutic principle. CAR-T therapy is therefore not a conceptual departure from transplant, but as a refinement of its central mechanism.Today, engineered T-cell therapies are widely used for the treatment of relapsed or refractory B-cell malignancies, including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, as well as B-cell acute lymphoblastic leukemia (ALL). In myeloma, CAR-T therapies are moving earlier in the disease course, and current research is investigating whether autologous stem cell transplant still has a place in the modern management of this disease. This evolution prompts a practical question: will CAR-T therapies replace HSCT?While CAR-T signals the next phase of cellular therapies, the daily clinical reality of transplantation reminds us that the field is still actively evolving. The current special issue crystallizes decades of accumulated experience in four real-world studies addressing core challenges of stem cell transplantation: infectious complications, post-transplant neoplasms, and post-relapse management.The first paper published in the current issue addresses letermovir prophylaxis for CMV in haploidentical HSCT recipients. Recent advances have shifted the preferred approach for cytomegalovirus prevention in allogeneic hematopoietic stem cell transplant recipients toward universal antiviral prophylaxis with letermovir for CMVseropositive patients. The work of Huang et. al. shows that although effective in preventing CMV viremia (32.1% vs 46.2%), LTV prophylaxis was associated with increased EBV reactivation (38.7% vs.13.7%) and a higher rate of post-transplant disease relapse (13.2% vs. 6.1%). This appears to coincide with delayed and functionally compromised T-lymphocyte recovery, suggesting a potential immunemediated mechanism of disease relapse.The second study from Sun et. al., expands the understanding of post-transplant viral enteritis by characterizing the most common pathogens involved.Beyond the well-recognized role of CMV, 13 additional pathogens were identified, with HHV-6 emerging as a far more common cause of viral enteritis than previously appreciated (37.3% of cases). Most cases occurred within 2-3 months post-HSCT, and coinfection was frequent, with over one quarter of patients harboring two or more viruses. CMV remained a major contributor (37.3% of cases) and, consistent with prior literature, was associated with inferior outcomes and increased non-relapse mortality.The third work by Rihani et.al covers a well recognized complication of transplantation, the risk of secondary neoplasms (SN). In their retrospective cohort of adult and pediatric patients, covering the period between January 2003 and December 2023, 1.6% of the patients developed a secondary malignancy. The majority of SNs were solid tumors (65.2%), with hematologic malignancies comprising 32.5%. The risk factors identified by the authors align with the existing literature and include the exposure to alkylating agents or topoisomerase II inhibitors, chronic GVHD and CMV reactivation.Finally, the fourth work included in our research topic addresses one of the most challenging clinical scenarios: the management of relapse after allo-HSCT for highrisk myeloid malignancies. Cheng et. al, describe the outcomes of a modern cohort of 106 AML patients relapsing after transplantation and demonstrate that the combination of venetoclax-hypomethylating agent strategy offers significantly superior outcomes compared with intensive chemotherapy. In their study, patients treated with the doublet combination achieved a significantly higher complete remission rate (56.6% vs 26.4%), higher MRD negativity rates(70.0% vs 35.7%) and extended median overall survival to 12.6 months versus 5.8 months.In conclusion, the landscape of cellular therapy is rapidly evolving, with engineered immune cell products increasingly shaping the future of curative treatment. The trajectory of innovation suggests a gradual narrowing of indications for classical stem cell transplantation as precision-engineered approaches expand. Yet, at present, HSCT remains an indispensable, lifesaving therapy. Ongoing progress in transplantation comes from deeper understanding and better prevention of shortand long-term complications, optimizing conditioning regimens, and improved supportive therapies. The future of the field will therefore not be defined by replacement, but by convergence: the continued evolution of transplantation and cellular engineering as complementary expressions of immune-based cure.

Background/Objectives: Corticosteroids are the standard first-line treatment for immune thrombocytopenia (ITP), a disorder that itself carries an excess risk of thrombosis, yet the evidence on corticosteroid-associated thrombotic risk in ITP has not been systematically synthesized. We aimed to estimate the association between corticosteroid exposure and venous (VT) and arterial thrombosis (AT) in ITP. Methods: Following PRISMA 2020 (PROSPERO CRD420261504746), we searched PubMed/MEDLINE, Scopus, Cochrane CENTRAL, LILACS, ClinicalTrials.gov, and WHO ICTRP from 2000 to 28 September 2026. Adjusted hazard ratios (HRs) were synthesized by study and outcome; crude odds ratios (ORs) were pooled with random-effects (REML) models within two subgroups (European cohorts; Asian hospital-based series). Risk of bias was assessed with JBI tools (and ROBINS-E for the adjusted cohorts) and certainty of evidence with GRADE. Results: Twelve studies (18,059 participants) were included, ten in the meta-analysis. Adjusted evidence came almost entirely from a French nationwide cohort (10,039 adults), in which time-varying corticosteroid exposure was associated with VT (HR 3.55, 95% CI 2.74–4.58; approximately 11 additional hospitalizations per 1000 person-years of exposure) but not with AT (HR 1.15, 0.94–1.41); an Italian cohort with ever-use exposure gave imprecise estimates (VT 2.2, 0.5–10.4; AT 5.3, 0.9–40.6). Crude ORs were 3.48 (1.73–7.01) in two European cohorts and 0.82 (0.59–1.14) in seven Asian hospital-based series, none of which adjusted for corticosteroid exposure (P for subgroup difference < 0.001). Two randomized trials comparing corticosteroid regimens reported no thrombotic events (0/328; exact 95% CI 0–1.1%). Certainty was low for VT and very low for the other outcomes. Conclusions: Low-certainty evidence, dominated by a single nationwide cohort, suggests that current corticosteroid exposure is associated with an approximately 3.5-fold higher hazard of VT in adults with ITP, without a consistent arterial association. Retrospective series that compare prior use without a defined exposure window may be less informative about the risk associated with current exposure. Corticosteroid exposure may reasonably be considered in VT risk assessment in ITP.