Case Report: Successful Treatment of Steroid-Refractory Immune Checkpoint Inhibitor-Related Pure Red Cell Aplasia With Cyclosporin.

Anemia associated with Immune checkpoint inhibitor (ICI) is usually hemolytic and regenerative. Cases of non-regenerative pure red cell aplasia are rare, and typically improve upon drug discontinuation and after corticotherapy. We herein report a case of nivolumab-related erythroblastopenia refractory to steroids in a melanoma patient that improved only after treatment with cyclosporin. Nivolumab had been well tolerated for 2 months after being introduced as an adjuvant treatment. Hemoglobin level then progressively decreased from 12.7 g/dl as baseline value to a nadir of 4.3 g/dL despite transfusion with a total of 29 packed red blood cells in 3 months. Extensive workup including repeated bone marrow examinations led to the diagnosis of pure red cell aplasia. Anemia persisted despite nivolumab discontinuation and over a month of corticotherapy, but improved dramatically 3 days after cyclosporin initiation and did not recur upon cyclosporin tapering. The patient remains cancer-free 9 months after nivolumab withdrawal. This case highlights the under-recognized risk of erythroblastopenia in patients treated with ICI and proves cyclosporin is a valid alternative for the treatment of steroid-refractory cases.

Short-course daptomycin lock and systemic therapy for catheter-related bloodstream infections: a retrospective cohort study in cancer patients with surgically implanted devices.

PURPOSE: Few in vivo studies have been reported describing efficacy and duration of antibiotic lock therapy (ALT) with daptomycin (DPT) for long-term catheter-related bloodstream infections (CRBSI) due to coagulase-negative staphylococci (CoNS). We retrospectively analysed the efficacy of short-course ALT with DPT in combination with systemic treatment (ST) for CoNS-associated CRBSI in our hospital. METHODS: Patients admitted for CoNS-associated CRBSI and treated with DPT as ALT and ST were retrospectively analysed. Success was defined as preservation of the catheter device 30 days after ending treatment. Catheter removal within 30 days of discontinuing treatment, for either microbiological documentation of CRBSI relapse or re-occurrence of unexplained fever, was considered as failure. RESULTS: Among 7610 patients admitted to the Departments of Internal Medicine/Infectious Diseases and Pneumology in Cannes from January 2013 to November 2015, we identified 28 episodes of CoNS-associated CRBSI. Seven patients died of cancer during follow-up. Thus, 21 episodes were analysed among 20 patients (median age 67 years, 12 males, all treated for neoplasia and carrying a port-a-cath® device). Staphylococcus epidermidis was the main agent responsible for CRBSI. Median duration of systemic and ALT DPT was 3 days, in combination with rifampin for 4 days and then generally followed by a switch to oral drugs, most frequently cotrimoxazole or linezolid, to achieve 14 median days of treatment. Clinical success and failure rates were 76% and 24%, respectively. CONCLUSIONS: Short-course DPT as ALT, combined with 14 days of ST, allowed conservative management of CoNS-associated CRBSI in surgically implanted-catheters in three-fourth of cases.

Autoimmune hemolytic anemia after nivolumab treatment in Hodgkin lymphoma responsive to immunosuppressive treatment. A case report.

The patients with refractory Hodgkin lymphoma have a poor prognosis. The nivolumab, an IgG4 monoclonal antibody inhibiting the program death 1 pathway has recently demonstrated its efficacy and its safety in patients with heavily pretreated refractory Hodgkin lymphoma. The side effects of this immunotherapy include autoimmune-like syndromes. A 75-year-old woman with no significant comorbidities was treated by nivolumab (3 mg/kg every 2 wk) as a third-line treatment for refractory Hodgkin lymphoma. A clinical response was observed with the first injection of nivolumab, with a reduction in superficial lymph nodes. After the second injection, the patient presented an authentic autoimmune hemolytic anemia with a profound anemia at 64 g/L and biologic characteristics of hemolysis (elevated unconjugated bilirubin, lactate dehydrogenase, and reticulocytes). The direct antiglobulin test was strongly positive for IgG antibodies, and the indirect antiglobulin test became positive with a very high level of autoantibodies. After 2 injections of nivolumab, the patient underwent a fluodeoxyglucose F 18 positron emission tomography-computed tomography, showing a partial response according to modified Cheson criteria. A treatment with prednisone (2 mg/kg), initiated after transfusion of 2 units of red blood cells, permitted the complete resolution of this autoimmune reaction after 3 months of corticotherapy. The fluodeoxyglucose F 18 positron emission tomography-computed tomography performed at the end of the corticotherapy showed a clear disease progression. Considering the very good response achieved after only 2 injections of nivolumab, the limited therapeutic resources for this old woman, and the complete resolution of the autoimmune hemolytic anemia, nivolumab was reintroduced at the same dose, with close clinical and biological monitoring. She received 6 more injections of nivolumab without recurrence of hemolysis.

Z-BeEAM (Ibritumomab tiuxetan, Bendamustine, Etoposide, Cytarabine, Melphalan) before autologous stem cell transplantation is safe and efficient for refractory large B-cell lymphoma.

BACKGROUND: Refractory or relapsed large B-cells lymphoma are usually treated with a high dose chemotherapy regimen followed by an autolougous stem cells transplantation. BEAM (carmustine, etoposide, cytarabine, melphalan) or more recently Z-BEAM (ibritumomab tiuxetan and BEAM) are commonly used regimens, but recently carmustine availability became difficult. The purpose of this study was to evaluate the feasibility and the safety of replacing carmustine by bendamustine in a new Z-BeEAM regimen (ibritumomab tiuxetan, bendamustine, etoposide, cytarabine, melphalan) prior to autologous stem cell transplantation. FINDINGS: This study was a retrospective analyze of six patients, with a median age of 60, treated by Z-BeEAM before autologous stem cell transplantation. We did not put in evidence any additional toxicities compared to conventional induction chemotherapy. The main toxicities were mucositis (3 grade III among 6 patients), gastrointestinal (2 grade III vomiting and 2 grade III diarrhea) and neutropenia (6 grade IV). Engraftment was successfully achieved for all patients. At the time of analysis of this study all patients were alive and in complete response based on the PET-CT evaluation. CONCLUSIONS: BeEAM plus ibritumomab tiuxetan combined regimen before autologous stem cell transplantation is feasible and safe in aggressive relapsing large B-cell lymphoma.

High-dose chemotherapy with carmustine, etoposide, cytarabine and melphalan followed by autologous stem cell transplant is an effective treatment for elderly patients with poor-prognosis lymphoma.

Autologous stem cell transplant (ASCT) after high-dose chemotherapy (HDT) increases overall survival when used in relapsed non-Hodgkin lymphoma (NHL) in patients under 65 years old. Limited experience is available for older patients. We present a retrospective analysis of 73 consecutive patients aged over 65 years treated for aggressive or relapsed lymphoma by HDT with carmustine, etoposide, cytarabine and melphalan (BEAM) at full dosage followed by ASCT. Patient data were obtained from medical charts from two institutions. Median age was 67 years (65-74). Significant comorbidities were present in 24.7% of patients. The median number of days for grade 4 neutropenia was 9 (5-18). The early treatment-related mortality rate (<100 days) was 2.7%. The estimated 2-year progression-free survival and overall survival rates were 67.2% and 78.5%, respectively. In conclusion, the full-dose HDT-ASCT regimen is feasible, safe and efficient in selected patients over 65 years old.

Visceral leishmaniasis due to Leishmania infantum with renal involvement in HIV-infected patients.

BACKGROUND: We describe histological, clinical findings and outcomes of renal involvement during Leishmania infantum infection in four HIV-infected patients in South France and North Italy hospital settings. CASES PRESENTATION: Four HIV-infected Caucasian patients (age 24-49) performed renal biopsy during episodes of visceral leishmaniasis. They presented severe immunosuppression, frequent relapses of visceral leishmaniasis during a follow-up period of several years and partial or complete recovery of renal function after anti-parasitic treatment. Main clinical presentations were nephrotic or nephritic syndrome and/or acute renal failure secondary to membranoproliferative type III glomerulonephritis or acute interstitial nephritis. Clinical outcome was poor, probably as a consequence of insufficient immuno-virological control of the HIV infection. CONCLUSIONS: Our findings suggest that the main histological findings in case of renal involvement due to Leishmania infantum infection in HIV-infected patients are type III MPGN and acute interstitial nephritis, with a histological specificity similar to that observed in canine leishmaniasis. Poor immune status in HIV-infected patients, altering the capacity for parasite clearance, and prolonged course of chronic active VL in this population may lead to the development of specific renal lesions.