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High-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) is the standard treatment for young patient ≤65 years with multiple myeloma (MM). The role of auto-SCT in elderly patients older than 70 years remains controversial in the era of novel agents and especially since the recent introduction of monoclonal antibodies (AbMo). In this study, we evaluated 12 patients with MM over 70 years old undergoing auto-SCT (elderly graft cohort) in seven centers of GIMEMA Working Group Lazio. We compared the baseline characteristics, treatment and outcome with 97 MM elderly patients who did not receive auto-SCT (nontransplant patients) from the same registry who were ≥ 70 years old, but did not undergo auto-SCT. The median progression free survival (PFS) for graft versus no-graft cohort was 56.4 versus 26.1 months, respectively. There was a trend for better PFS among graft compared to nontransplant patient (p = .1). On the other hand, the median overall survival for transplant versus nontransplant cohort was 107.6 versus 49.5 months (p = .02). Despite the small number of patients aged ≥70 years and ≤74 years, it seems that auto-SCT is well tolerated, safe and effective. Therefore, we propose that it should be considered an important treatment option in the era of new drugs in elderly fit patients with MM., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite the availability of several antiemetics, clinical findings show that control of chemotherapy-induced nausea and vomiting (CINV) continues to be a serious concern for hematological patients, mainly for those receiving multiple-day (MD) and high-dose (HD) chemotherapy (CT). For CINV prophylaxis, 5-hydroxytryptamine type-3 receptor antagonists (5HT 3 -RAs) and neurokinin 1 receptor antagonists (NK 1 -RAs) are usually administered together with dexamethasone, which may increase the risk of serious infections in patients undergoing myeloablative treatment. The rationale of this multicenter, open-label and phase IIa study was to explore the efficacy of multiple doses of NEPA (netupitant/palonosetron) given as an every-other-day regimen without dexamethasone in preventing CINV in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma (R/R-NHL), eligible for autologous stem cell transplantation (ASCT) and treated with MD-HD-CT. Seventy patients participated to the study. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. The CR values were 87.1% (primary endpoint, overall phase: days 1-8), 88.6% (acute phase: days 1-6), and 98.6% (delayed phase: days 7-8), while complete control (CR with no more than mild nausea) was 85.7% (overall phase), 88.6% (acute phase), and 95.7% (delayed phase). Moderate and severe episodes of nausea were reported by less than 10% of patients in the overall phase and less than 5% in both the acute and delayed phases. Regarding safety, NEPA was well tolerated with only one adverse event (constipation) evaluated as possibly related to NEPA administration. In conclusion, our study demonstrated that multiple alternate dosing of NEPA without the addition of dexamethasone is highly effective for preventing nausea and vomiting in this difficult setting, with a good tolerability profile.

Introduction: High-dose melphalan (HDMel) is the most common conditioning chemotherapy regimen for autologous stem cell transplantation (SCT) in patients affected by multiple myeloma (MM). No consensus exists for the emetogenicity or prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in this regimen., Methods: Data on the incidence and efficacy/safety of CINV prophylaxis among patients affected by MM undergoing autologous SCT with the HDMel regimen was extracted from electronic databases and analyzed., Results: Eleven studies involving multiple CINV prophylaxis regimens were identified and included. No consensus on HDMel emetogenicity was reached, but most studies summarized the emetogenicity as moderate-high risk. An aprepitant-based three-drug regimen (aprepitant + serotonin receptor antagonist (5HT3RA) + dexamethasone) showed better efficacy than a two-drug regimen (5HT3RA + dexamethasone) for CINV prevention without increasing the frequency in adverse events., Conclusions: The aprepitant-based three-drug regimen should be the regimen of choice for CINV prophylaxis for MM patients undergoing autologous SCT with HDMel conditioning.

Background: membranous glomerulopathy (MG) is an immunomediated disorder which accounts for the most common cause of nephrotic syndrome (NS) following allogeneic hematopoietic stem cell transplantation (HSCT)., Objective and Methods: to provide an update on the issue by reviewing pertinent literature on the MEDLINE database., Results: sixty-nine post allogenic HSCT patients (42 male) with MG were identified. The median age was 43 (5 to 68) years. Time interval from allogenic HSCT to MG diagnosis ranged from 3 to 134 months (median 17). Most MG patients had a history of acute (70%) or chronic (84%) graft versus host disease (GVHD). Corticosteroids and cyclosporine were the most common therapeutic agents used in this setting; alternative therapies, including rituximab, were given to a lower number of patients. Outcome data were available in 64 out of 69 MG patients; 38 (59%) and 18 (28%) patients achieved a complete and a partial response respectively, whereas treatment failure was recorded in the remaining 8 (13%)., Conclusion: MG after allogenic HSCT appears to be associated with a sub clinical or overt cGVHD, which follows the discontinuation of immunosuppressive prophylaxis. Although a standard therapeutic approach has not been established, the application of available measures can induce favorable response in more than 80% of affected patients, but treatment-failure and progressive deterioration of the renal function may occur in about one fifth of cases.

Severe pain syndromes may be recorded during all phases of haematopoietic stem cell transplantation (HSCT) for haematological malignancies: from stem cell mobilization to the long-term post transplant period. Although the major cause of pain in the setting of HSCT is injury to mucosal tissues induced by the conditioning regimen, pain from several other causes has been reported. In this paper, we review pain and its management in the setting of HSCT.

Mucosal barrier injury (mucositis) is a common complication of many treatments used in hematologic malignancies, affecting most patients whose neoplasms are treated with intensive chemotherapy, and virtually all those receiving myeloablative conditioning regimens prior to hematopoietic stem cell transplantation. Mucositis has been identified as a critical risk factor for infections and is a major driver of analgesic and total parenteral nutrition use. Patients with this complication require careful analgesic therapy, additional nursing care and longer hospitalization. To date, the measures to prevent and treat this potentially devastating complication are inadequate and limited to the control of pain, infections, bleeding and nutrition. Nevertheless, in the last decade, a better insight into the pathogenesis of the mucosal damage has led to the development of novel therapeutic options which potentially could allow a targeted approach to mucositis.

CBV and BEAM are the two most frequently used regimens for patients with lymphoma undergoing autologous hematopoietic stem-cell transplantation (ASCT). This study compared their morbidity and transplant-related mortality (TRM) in 113 patients with non-Hodgkin's lymphoma (69) and Hodgkin's disease (44) undergoing ASCT between 1990 - 2004. CBV (cyclophosphamide, 6000 mg m(-2); VP-16, 750 mg m(-2); and high-dose BCNU, 800 mg m(-2)) was administered to 75 patients and 38 received BEAM (BCNU, 300 mg m(-2); VP-16, 800 mg m(-2); cytarabine, 800 mg m(-2); melphalan, 140 mg m(-2)). Patients in the BEAM group had a significantly higher median age (p = 0.002) and were more heavily treated before ASCT (p = 0.003). More patients showed active disease at transplant in the BEAM group (p = 0.04). Sinusoidal obstruction syndrome (SOS) was more frequent in the CBV group (11% vs 0%, p = 0.048). There were 20 (18%) transplant-related deaths, 18 in the CBV and two in the BEAM group. Infectious complications (12 patients, seven with pneumonia) and SOS (four) were the most frequent causes of death. The cumulative incidences of TRM were 25% in the CBV and 7% in the BEAM group (p = 0.02). CBV thus produced a higher incidence of SOS and TRM than BEAM in this series.

High-dose chemotherapy and radiation used as a preparative regimen for allogeneic stem cell transplantation (SCT) produces a considerable morbidity and mortality. An alternative strategy, developed to reduce transplant-related toxicity and to induce graft versus malignancy effect in the presence of full hematopoietic engraftment, includes the application of RIC that provide sufficient immunosuppression. We studied the efficacy and toxicity of RIC followed by allogeneic SCT in elderly patients or with relative contraindications to conventional SCT. In all, 22 patients with hematologic malignancies and HLA-identical sibling donors were included in this study. All patients were either refractory to therapy or beyond first complete remission (CR). The majority of patients received fludarabine 120 mg/m(2)+thiotepa 10 mg/kg as conditioning regimen and cyclosporine as graft versus host disease (GVHD) prophylaxis. Organ toxicity was acceptable and all evaluable patients achieved engraftment. Three patients (15%) showed grade >II aGVHD; extensive chronic GVHD occurred in three out of 15 evaluable patients (20%). With median follow-up of 63.5 months, survival was 31%, disease-free survival (DFS) was 23%. All the durable responses occurred in patients who developed GVHD. Transplant related mortality (TRM) at 100 days was 27.3%, 67% of that caused by infections, while 6-year cumulative incidence of TRM was 38%. Our data show that RIC: (1). allows the engraftment of HLA-matched hematopoietic stem cells (2). provide durable responses in patients not eligible for conventional SCT exploiting the graft-versus-malignancy effect and (3). is loaded by an high rate of fatal infections.

Chronic graft versus host disease (cGVHD) is a frequent complication of allogeneic stem cell transplantation. Extensive musculoskeletal and skin involvement may induce severe functional impairment, disability and quality of life deterioration. Physical rehabilitation is recommended as ancillary therapy in these forms, but experiences are sparse. A 39-year-old man affected by musculoskeletal and skin chronic graft versus host disease (cGVHD) was treated with a homecare-based motor rehabilitation program during palliation for disease progression. Significant functional improvement was obtained. Motor rehabilitation should be strongly considered for patients with musculoskeletal cGVHD, both in the palliative and in the curative phase of disease. [ABSTRACT FROM AUTHOR]