Feasibility of allogeneic hematopoietic stem cell transplantation in advanced age.

Although it is known that increasing age is associated with increased morbidity and mortality in allogeneic transplantation (allo-HSCT), individualization of the process may allow to perform it in progressively older patients.This study analyzed the outcome of 97 patients older than 60 years with a first allo-HSCT performed at our institution between 2011 and 2019.Median age was 66 years (range 60-79) and 15.4% were older than 70 years. The most frequent diagnosis was acute leukemia (50.5%), and 58.8% received a myeloablative conditioning. With a median follow-up of 33.9 months (range 7.9-111.5), at 3-years overall survival (OS) was 50%; progression-free survival (PFS), 46%; cumulative incidence of relapse, 22%; and non-relapse mortality (NRM), 32%. There were no significant differences in OS (p = 0.415), PFS (p = 0.691), cumulative incidence of relapse (p = 0.357) or NRM (p = 0.658) between patients of 60-64 years (n = 37), 65-69 (n = 45) and ≥ 70 years (n = 15). No differences were observed either depending on the intensity of the conditioning regimen in terms of OS (p = 0.858), PFS (p = 0.729), cumulative incidence of relapse (p = 0.416) or NRM (p = 0.270).In conclusion, older adults can safely and effectively undergo allo-HSCT with proper patient selection and individualized transplantation procedures.

6q deletion in Waldenström macroglobulinaemia negatively affects time to transformation and survival.

Deletion of the long arm of chromosome 6 (del6q) is the most frequent cytogenetic abnormality in Waldenström macroglobulinaemia (WM), occurring in approximately 50% of patients. Its effect on patient outcome has not been completely established. We used fluorescence in situ hybridisation to analyse the prevalence of del6q in selected CD19+ bone marrow cells of 225 patients with newly diagnosed immunoglobulin M (IgM) monoclonal gammopathies. Del6q was identified in one of 27 (4%) cases of IgM-monoclonal gammopathy of undetermined significance, nine of 105 (9%) of asymptomatic WM (aWM), and 28/93 (30%) of symptomatic WM (sWM), and was associated with adverse prognostic features and higher International Prognostic Scoring System for WM (IPSSWM) score. Asymptomatic patients with del6q ultimately required therapy more often and had a shorter time to transformation (TT) to symptomatic disease (median TT, 30 months vs. 199 months, respectively, P < 0·001). When treatment was required, 6q-deleted patients had shorter progression-free survival (median 20 vs. 47 months, P < 0·001). The presence of del6q translated into shorter overall survival (OS), irrespective of the initial diagnosis, with a median OS of 90 compared with 131 months in non-del6q patients (P = 0·01). In summary, our study shows that del6q in IgM gammopathy is associated with symptomatic disease, need for treatment and poorer clinical outcomes.

Response to Novel Drugs before and after Allogeneic Stem Cell Transplantation in Patients with Relapsed Multiple Myeloma.

Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P < .001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P < .001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment.

Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma.

Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not yet been explored. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated according to immunoglobulin recovery at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression free, 88 patients (52%) showed immunoglobulin recovery and 81 (48%) did not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; Hazard Ratio: 0.45, 95%Confidence Interval: 0.31-0.66; P<0.001), and improved overall survival (11.3 vs. 7.3 years; Hazard Ratio: 0.45, 95%Confidence Interval: 0.27-0.74; P=0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: nine months and one year. In conclusion, the recovery of polyclonal immunoglobulins one year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival.

Multiple primary cutaneous plasmacytoma a decade after a nasal solitary extramedullary plasmacytoma: a puzzling case.

Primary cutaneous plasmacytoma should be in the differential diagnosis in case of solitary or multiple erythematous-violaceous nodules or papules. The diagnosis relies on clinical, histological, and immunochemical findings, without underlying evidence of multiple myeloma. Treatment should be individualized, and agents such as bortezomib or lenalidomide have shown to be effective.