Sexuality- and Fertility-Related Issues in Women after Allogeneic Hematopoietic Stem Cell Transplantation.

Sexual dysfunction and fertility related issues appear as major post-allogeneic hematopoietic stem cell transplantation (HSCT) late effects in young women, with a heavy impact on quality of life. The objective of the present study was to evaluate the impact of disease and treatments on sexual quality of life, ovarian function, and family planning initiatives in the context of allogeneic HSCT. Between January 2014 and January 2016, adult female patients who underwent HSCT before age 35 and had been followed for more than 2 years in our center were offered participation in the study through a self-reported survey and/or ovarian function assessment if age <40 at inclusion. A total of 63 patients were included, with a median age of 23.4 years at transplantation and 30.9 years at inclusion. Twenty-nine patients (46%) underwent HSCT for acute leukemia and 16 (25%) underwent HSCT for aplastic anemia (AA). The conditioning regimen was myeloablative conditioning (MAC) in 37 patients (59%) and reduced-intensity conditioning (RIC) in 26 (41%). Fifty-eight patients completed the survey, and 34 were evaluated for ovarian function. Symptoms of hypoestrogenism were reported by 86% of the patients and changes in sexual life were reported by 76%, due mainly to low sex drive, negative impact of infertility problems, physical sequelae, and loss of self-confidence. Premature ovarian failure (POF) occurred in 74% of patients and was significantly associated with conditioning regimen (MAC versus RIC; P = .001) and baseline disease (bone marrow failure versus acute leukemia versus others; P < .001). However, one-half of the patients developed a POF despite the use of a RIC regimen. For 27 patients (47%), disease and treatments modified their desire for pregnancy, due mainly to fear of relapse and of disease transmission to offspring. Thirteen pregnancies were reported (21%), of which 8 were spontaneous and 5 were obtained through assisted reproductive technologies, mainly oocyte donation. With a median post-transplantation follow-up of 12.2 years, the 10-year cumulative incidence of first pregnancy was 16.6% (95% CI, 8.8-30.0). Among 20 patients (32%) who engaged in a family planning initiative, 13 (65%) succeeded in having children: 11 got pregnant and 2 adopted. Sixteen patients benefited from fertility preservation techniques consisting of ovarian tissue cryopreservation, and a single autologous ovarian tissue transplantation had been performed at the time of this report. This study shows a strong impact of disease and treatments on sexual quality of life, ovarian function, and family planning initiatives in the context of HSCT. It demonstrates the need to improve clinicians' awareness of sexual health- and fertility-related issues after HSCT. The difficulty of predicting ovarian function and fertility issues after RIC supports wide indications of pretransplantation fertility preservation. Evaluation of the use of cryopreserved ovarian tissues is warranted.

Poor outcome associated with mucormycosis in critically ill hematological patients: results of a multicenter study.

BACKGROUND: Mucormycosis is an emerging fungal infection that may lead to multi-organ failure, especially in patients with hematological malignancies (HM). We performed a retrospective, cohort study, in five intensive care units (ICU) to assess the outcome of critically ill patients with HM and mucormycosis between 2002 and 2018. The secondary objective was to identify prognostic factors in this setting. RESULTS: Twenty-six patients were included with a median age of 38 years [IQR, 26-57]). Acute leukemia was the most frequent underlying disease (50%). Nine patients (35%) underwent allogeneic stem cell transplantation (SCT). Nineteen patients (73%) had neutropenia and 16 (62%) had received steroids. The main reason for admission was acute respiratory failure (n = 14, 54%) followed by shock (n = 5 19%). The median SOFA score at admission was 7 [5-8]. According to EORTC/MSG criteria, mucormycosis was "proven" in 14 patients (54%), "probable" in 5 (19%) and "possible" in 7 (27%) in whom diagnosis was made by qPCR. Rhizopus and Mucor were the most frequent documented species. Seven patients (27%) had concurrent Aspergillus infection. Mucormycosis was diagnosed 1 day [-4 to + 6] after ICU admission. Sixteen patients (62%) had pulmonary involvement and ten (38%) rhino-cerebral involvement. Infection was disseminated in eight patients (31%). Twenty-two patients (85%) were treated with liposomal amphotericin B; 12 (46%) received antifungal combination including posaconazole in 7. Eight patients (31%) underwent curative surgery. Twenty-one patients (81%) required invasive mechanical ventilation (IMV), 18 (69%) vasopressors, and 9 (35%) renal replacement therapy. ICU and hospital mortality rates were 77% and 88%, respectively. The median overall survival was 9 days [3-22]. IMV was strongly associated with ICU mortality (p < 0.001) Three variables were associated with day 90 mortality in a Cox model including allogeneic SCT (HR 4.84 [95% CI 1.64-14.32]), SOFA score (1.19 [1.02-1.39]) and dual therapy (3.02 [1.18-7.72]). CONCLUSIONS: Mucormycosis is associated with a high mortality rate in patients with HM, especially in allogeneic SCT recipients. Benefit of ICU management in these patients should be assessed before admission and strategies aiming to improve these patients' outcome are urgently needed.

Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura.

Preemptive rituximab infusions prevent relapses in immune thrombotic thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However, the long-term outcome of these patients and the potential adverse events of this strategy need to be determined. We report the long-term outcome of 92 patients with iTTP in clinical remission who received preemptive rituximab after identification of severe ADAMTS13 deficiency (activity <10%) during the follow-up. Thirty-seven patients had >1 iTTP episode, and the median cumulative relapse incidence before preemptive rituximab was 0.33 episode per year (interquartile range [IQR], 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episodes per year (IQR, 0-1.32; P < .001). After preemptive rituximab, ADAMTS13 activity recovery was sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65), and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial improvement. ADAMTS13 activity usually improved with additional courses of preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained undetectable after the first rituximab course, but retreatment was efficient in 6 of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was associated with a change in ADAMTS13 conformation in respondent patients. Finally, in the group of 23 historical patients with iTTP and persistently undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP during remission is associated with a higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.

Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia.

BACKGROUND: Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results. METHODS: The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia. RESULTS: The median age of the patients was 46 years (range, 15-57 years). Sorafenib was introduced at a median of 70 days (range, 29-337 days) after HSCT. The median treatment duration was 8.4 months (range, 0.2-46 months). Eleven patients experienced treatment toxicities, mainly of grade 1 to 2 (graded according to the National Cancer Institute Common Toxicity Criteria [version 4.0]). Dose reduction or withdrawal was required in 4 patients and 4 patients, respectively. The persistence of toxicity prompted treatment withdrawal in 1 patient. Clinical improvement followed dose modifications. Thirteen patients experienced chronic graft-versus-host disease (limited in 9 patients and extensive in 4 patients), resulting in dose reduction in 5 patients followed by withdrawal in 1 of these individuals. At a median follow-up of 18 months (range, 4-48 months), 25 patients were alive (all of whom were in complete molecular remission) and 18 were still receiving treatment, with 1-year overall survival and progression-free survival rates of 92% ± 6% and 92% ± 5%, respectively. CONCLUSIONS: Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT. Cancer 2017;123:2867-74. © 2017 American Cancer Society.