RESUMEN
Despite the high cure rate with initial therapy, approximately 10% of Hodgkin lymphoma (HL) patients are refractory to initial treatment, and up to 30% of patients will relapse after achieving initial complete remission. Despite promising initial results of treatment by immune checkpoint inhibitors, most patients will eventually progress. We analyzed 62 adult patients with relapsed or refractory HL (rrHL) treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in one of three University Hospitals of Switzerland (Zurich, Basel, and Geneva) between May 2001 and January 2020. The primary endpoint was overall survival (OS). Secondary endpoints were relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence, which were assessed in univariate analysis. The median follow-up was 61 months (interquartile range 59-139). The 2- and 5-year OS was 54% (standard error (SE) ±12) and 50.2% (SE ±13.3), respectively, and the 2- and 5-year RFS was 40.7% (SE ±16.3) and 34.4% (SE ±19.0), respectively. NRM was 23.1% (SE ±2.2) and 27.4% (SE ±2.5) at 2 and 5 years, respectively. The cumulative incidence of relapse was 36.1% (SE ±5.6) at 2 years and 38.2% (SE ±6.6) at 5 years. Our analysis of allo-HSCT outcomes in the context of rrHL shows encouraging OS and RFS rates, with the mortality rate reaching plateau at 50% at 2 years after allo-HSCT. This confirms that allo-HSCT still remains as a potentially curative option for half of patients with rrHL.
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BACKGROUND: Acquired hemophilia A is a rare autoimmune disease with clinically often significant bleeding diathesis resulting from circulating autoantibodies inhibiting coagulation factor VIII. Half of acquired hemophilia A cases are associated with an underlying disorder, such as autoimmune diseases, cancer, or use of certain drugs, or occur during pregnancy and in the postpartum period. In the other half, no underlying cause is identified. An association of acquired hemophilia A with plasma cell neoplasm seems to be extremely rare. CASE PRESENTATION: We describe a case of a 77-year-old Swiss Caucasian man who was diagnosed with acquired hemophilia A and smoldering multiple myeloma as an underlying cause. Acquired hemophilia A was treated with prednisolone, cyclophosphamide, and immunoadsorption. Extensive workup revealed a plasma cell neoplasm as the only disorder associated with or underlying the acquired hemophilia A. For long-term control of acquired hemophilia A, we considered treatment of the plasma cell neoplasm necessary, and a VRD (bortezomib, lenalidomide, and dexamethasone) regimen was initiated. Due to multiple complications, VRD was reduced to VRD-lite after two cycles. After nine cycles of induction therapy and five cycles of consolidation therapy, the patient is in complete remission of his acquired hemophilia A and very good partial remission of the plasma cell neoplasm. We conducted a literature review to identify additional cases of this rare association and identified 15 other cases. Case descriptions, including the sequence of occurrence of acquired hemophilia A and plasma cell neoplasm , treatment, evolution, and outcome are presented. DISCUSSION AND CONCLUSIONS: Our case, together with 15 other cases described in the literature, underscore the possibility of plasma cell neoplasm as an underlying cause of acquired hemophilia A. Physicians should consider including protein electrophoresis, immunofixation, and analysis of free light chains in laboratory diagnostics when treating a patient with acquired hemophilia A. The occurrence of excessive and unexplained bleeding in patients diagnosed with plasma cell neoplasm should raise suspicion of secondary acquired hemophilia A and trigger the request for coagulation tests, particularly in patients treated with immunomodulatory drugs such as thalidomide or lenalidomide. Additionally, early intervention with immunoadsorption can be lifesaving in cases with high-titer factor VIII inhibitors, especially when surgical interventions are necessary.
Asunto(s)
Hemofilia A , Mieloma Múltiple , Plasmacitoma , Anciano , Factor VIII , Hemofilia A/complicaciones , Hemofilia A/diagnóstico , Hemofilia A/tratamiento farmacológico , Humanos , Lenalidomida , Masculino , TalidomidaRESUMEN
The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2mg, and tropisetron 5mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.