Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience.

PURPOSE: To provide insights into the diagnosis and management of therapy-related myeloid neoplasms (t-MN) following PARP inhibitors (PARPi). EXPERIMENTAL DESIGN: In a French cancer center, we identified and described the profiles of 13 t-MN diagnosed among 37 patients with ovarian cancer referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post-PARPi among 37 t-MN post ovarian cancer according to PARPi exposure. Finally, we described 69 t-MN post-PARPi in a national cohort. RESULTS: From 2016 to 2021, cumulative incidence of t-MN was 3.5% (13/373) among patients with ovarian cancer treated with PARPi. At time of hematologic consultation, patients with t-MN had a longer PARPi exposure (9 vs. 3 months, P = 0.01), lower platelet count (74 vs. 173 G/L, P = 0.0005), and more cytopenias (2 vs. 1, P = 0.0005). Compared with t-MN not exposed to PARPi, patients with t-MN-PARPi had more BRCA1/2 germline mutation (61.5% vs. 0%, P = 0.03) but similar overall survival (OS). In the national cohort, most t-MN post-PARPi had a complex karyotype (61%) associated with a high rate of TP53 mutation (71%). Median OS was 9.6 months (interquartile range, 4-14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR, 1.046; P = 0.02), olaparib compared with other PARPi (HR, 5.82; P = 0.003) and acute myeloid leukemia (HR, 2.485; P = 0.01) were associated with shorter OS. CONCLUSIONS: In a large series, we described a high incidence of t-MN post-PARPi associated with unfavorable cytogenetic and molecular abnormalities leading to poor OS. Early detection is crucial, particularly in cases of delayed cytopenia.

Autoimmune hemolytic anemia and nodular lymphocyte-predominant hodgkin lymphoma: a rare association.

Autoimmune hemolytic anemia (AIHA) has been associated with chronic lymphocytic leukemia, non-Hodgkin lymphoma, and classical Hodgkin lymphoma, but to the best of our knowledge, the association of AIHA and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) has not been reported previously. A 20-year-old woman presented with conjunctival jaundice, fever, asthenia, and hemoglobin 9.2 g/dL revealing IgG-mediated warm antibody AIHA. Computed tomography (CT) scan and positron-emission tomography (PET) scan showed mediastinal and axillary lymph nodes with increased [(18)F]-fluorodeoxyglucose uptake. A mediastinal lymph node was biopsied during mediastinoscopy, and NLPHL was diagnosed by an expert hematopathologist. The hemoglobin level declined to 4.6 g/dL. The treatment consisted of four 28-day cycles of R-ABVD (rituximab 375 mg/m(2) IV, adriamycin 25 mg/m(2) IV, bleomycin 10 mg/m(2) IV, vinblastine 6 mg/m(2) IV, and dacarbazine 375 mg/m(2) IV, each on days 1 and 15). Prednisone was progressively tapered over 10 weeks. After the first chemotherapy cycle, the hemoglobin level rose to 12 g/dL. After the four cycles, PET and CT scans showed complete remission (CR). At the last followup (4 years), AIHA and NLPHL were in sustained CR.

Persistent poor long-term prognosis of allogeneic hematopoietic stem cell transplant recipients surviving invasive aspergillosis.

BACKGROUND: Voriconazole treatment increases early survival of allogeneic hematopoietic stem cell transplant recipients with invasive aspergillosis. We investigated whether this survival advantage translates into an increased long-term survival. DESIGN AND METHODS: This retrospective study involved all patients with an invasive aspergillosis diagnosis transplanted between September 1997 and December 2008, at the Saint-Louis Hospital, Paris, France. The primary end point was survival up to 36 months. Survival analysis before and after 12 weeks, as well as cumulative incidence analysis in a competing risk framework, were used to assess the effect of voriconazole treatment and other factors on mortality. RESULTS: Among 87 patients, 42 received first-line voriconazole and 45 received another antifungal agent. Median survival time was 2.6 months and survival rate at 36 months was 18%. Overall, there was a significant difference in the survival rates of the two groups. Specifically, there was a dramatic difference in survival rates up to ten months post-aspergillosis diagnosis but no significant difference after this time. Over the first 36 months as a whole, no significant difference in survival rate was observed between the two groups. First-line voriconazole significantly reduced aspergillosis-attributable mortality. However, first-line voriconazole patients experienced a significantly higher probability of death from a non-aspergillosis-attributable cause. CONCLUSIONS: Although the prognosis for invasive aspergillosis after stem cell transplantation has dramatically improved with the use of voriconazole, this major advance in care does not translate into increased long-term survival for these severely immunocompromised patients.