Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

Independent risk factors for COVID-19-associated coagulopathy.

OBJECTIVE: Past three years since the beginning of the outbreak, we have obtained satisfactory data on COVID-19. However, data on risk factors of COVID-19-associated coagulopathy (CAC) are extremely limited. Prediction of CAC might be a game changer since it is related to poor prognosis. Seeking independent risk factors for CAC was the main aim of the study. PATIENTS AND METHODS: 510 hospitalized COVID-19 patients were retrospectively screened. Forty-eight of them were excluded due to irrelevant D-dimer or ferritin elevation. The remaining patients were stratified into three groups as overt coagulopathy, significant pulmonary microthrombosis, and patients without coagulopathy. The overt coagulopathy group included cases with macrothrombosis or disseminated intravascular coagulation (DIC). The significant pulmonary microthrombosis group covered the cases that had clinical deterioration with simultaneous marked D-dimer elevation. The group of patients without coagulopathy included the asymptomatic patients with normal or elevated D-dimer levels. RESULTS: Overt coagulopathy developed in 3.2% and significant pulmonary microthrombosis in 10.1% of the patients. In the multivariate analysis, not receiving low molecular weight heparin (LMWH) (p=0.002), a level of D-dimer >15,000 U/ml (p=0.013) were associated with overt coagulopathy. In addition, levels of initial LDH >480 IU/L (p=0.022) and initial ferritin >1,000 ng/ml (p=0.036) were associated with significant pulmonary microthrombosis. Not receiving LMWH (p=0.001) was also associated with significant pulmonary microthrombosis, when multivariate analysis was performed by the parameters with a p-value <0.1 in the univariate analysis. Furthermore, all cases with DIC had Gram-negative bacterial sepsis. CONCLUSIONS: Not receiving LMWH, high levels of D-dimer, initial LDH, and initial ferritin are independent risk factors for CAC. DIC does not appear to develop based on COVID-19.

An unusual presentation of a chronic lymphocytic leukemia patient with 17p deletion after reduced-intensity transplantation: Richter syndrome and concomitant graft-versus-host disease--case report.

Chronic lymphocytic leukemia (CLL) patients with 17p deletion comprise a challenging subgroup associated with poor overall survival. These patients should be treated with alternative strategies. Reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) can achieve long-term remission in this ultra-high-risk CLL group. Herein, we described a CLL patient with 17p deletion who developed Richter syndrome with extranodal involvement of the liver soon after RIC allo-SCT despite apparent acute graft-versus-host disease. The majority of chronic lymphocytic leukemia (CLL) patients respond well to chemoimmunotherapy. Patients who show ultra-high-risk genetics, such as 17p deletions, comprise a challenging subgroup of patients with poor response to chemoimmunotherapy and median life expectancy <2-3 years at the time of first-line treatment. Current treatment approaches for patients with 17p deletion include agents acting independently from the DNA damage pathway, such as alemtuzumab and high-dose corticosteroids. RIC allo-SCT for consolidation can achieve long-term remission in this ultra-high-risk CLL group.(1,2) Richter syndrome (RS) represents the clinicopathologic transformation of CLL to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL).(3) RS appearing after allo-SCT can be managed by tapering of immunosuppression, followed by dose-escalated donor lymphocyte infusion titrated to the degree of leukemia response and graft-versus-host disease (GVHD) encountered.(4) Herein, we describe a CLL patient with 17p deletion who developed RS with extranodal involvement of the liver soon after RIC allo-SCT despite apparent acute GVHD (aGVHD).

Severe bone marrow failure due to valganciclovir overdose after renal transplantation from cadaveric donors: four consecutive cases.

Valganciclovir is an l-valyl ester pro-drug of ganciclovir that was initially used to treat cytomegalovirus (CMV)-associated retinitis in patients with human immunodeficiency virus. Currently, it is also indicated for the prevention of CMV disease in solid-organ transplantation. It is primarily eliminated via the kidneys through glomerular filtration and tubular secretion. Decreased renal function results in decreased drug clearance. Valganciclovir has been reported to cause usually mild to moderate hematologic adverse effects such as leukopenia, neutropenia, anemia, thrombocytopenia, and pancytopenia. Severe and fatal bone marrow depression has been described in 1 adult patient. Herein, we describe the cases of 4 patients with end-stage renal disease who underwent cadaveric renal transplantation and received valganciclovir prophylaxis for CMV at a standard dose of 900 mg/d despite persistant renal failure. This therapy resulted in severe bone marrow failure after 18 to 20 days in all 4 patients, with fatal infections in 2 patients. This report demonstrates the in vivo pharmacodynamics of valganciclovir overdose in terms of hematotoxicity in the setting of renal impairment. Valganciclovir, as its derivative ganciclovir, should be used cautiously in patients with renal impairment.