Molecular Demonstration of a Pneumocystis Outbreak in Stem Cell Transplant Patients: Evidence for Transmission in the Daycare Center

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection in hematology. Although occasionally reported, the role of interhuman transmission of P. jirovecii in PCP, compared to that of reactivation, remains an unresolved question; the recommendation to isolate PCP patients in the hematology ward are not well evidence-based. Following an unexpected increase in the number of febrile pneumonia patients with P. jirovecii DNA detected in respiratory samples in our hematology ward, we explored 12 consecutive patients from November 2015 to May 2016. Genotyping of P jirovecii was performed using microsatellite markers. The frequency of simultaneous occupancy of these 12 patients in the same unit on the same day from 4 months prior to the first diagnosis was recorded. In three patients, the P. jirovecii genotype could not be determined because DNA was insufficient. One rare single genotype (Gt2) was found in four of the other nine, all allogeneic stem cell transplant recipients. The transmission map showed that these 4 patients had multiple opportunities to meet on the same day (median, 6.5; range, 4–10) at the daycare center. It was much less among the eight non-Gt2 patients (median, 1; range, 0–9; P = 0.048). This study, based on modern molecular technics, strongly suggests that interhuman transmission of P. jirovecii between allogeneic stem cell transplant recipients is possible. P. jirovecii DNA detected in respiratory specimens supports that isolation and respiratory precautions be recommended in such cases in the hematology ward

Regulatory T-cell depletion in donor lymphocyte infusions for haematological malignancies: long-term outcomes from a prospective study.

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Immunogenicity and safety of the meningococcal B recombinant (4CMenB) vaccine in allogeneic hematopoietic cell transplantation recipients

International audienceObjectivesDespite a high risk of invasive meningococcal (Men) disease, there is no published data on any MenB vaccine after hematopoietic cell transplantation (HCT). We investigated the immunogenicity and safety of the 4CMenB recombinant vaccine (Bexsero) in adult HCT recipients.MethodsPatients were eligible from 6 months post-HCT to receive 2 4CMenB doses at 2-month intervals. Sera were collected at baseline, 1 month after the second dose, and 12 months after enrolment. The serum bactericidal activity (SBA) using human complement (hSBA) was assessed against fHbp, NadA, PorAP1.4, and NHBA antigens. The vaccine response was defined by one criterion for one vaccine antigen: (1) in patients with a hSBA titer <4 at baseline: a titer ≥4; (2) in patients with a hSBA titer ≥4 at baseline: at least a 4 time increase.ResultsForty (40) patients were included at a median of 2.14 (0.57–13.03) years posttransplant. At baseline, most patients (32/40, 80%) had hSBA titers <4 for all vaccine antigens. After 2 vaccine doses, the proportion of patients with a titer ≥4 was significantly increased for fHbp (23/40, 57.5%), NadA (25/40, 62.5%), and PorA (31/40, 77.5%) but not for NHBA for which only 6 of 40 (15%) patients responded. Of patients, 36 out of 0 (90%) were responders to ≥1 antigen. However, 9 months later, only 23 out of 37 (62.2%) patients were still seroprotected. No severe adverse event was observed.DiscussionThe response rate of 90% for ≥1 vaccine antigen and our safety data supports the 4CMenB vaccination of HCT recipients from 6 months after transplant with 2 doses

Toxoplasmosis as an Early Complication of Allogeneic Hematopoietic Cell Transplantation

International audienceAmong 419 consecutive allogeneic hematopoietic cell transplant recipients, we observed 17 (4.0%) cases of toxoplasmosis at a median time of day 45 (range, 6 to 322) after transplant. Seven of these 17 cases occurred before day 30 after transplant. Because of the lack of PCR screening and trimethoprim-sulfamethoxazole prophylaxis before engraftment, the diagnosis of toxoplasmosis was late, and 5 of these 7 patients died. Analyzing these cases, early Toxoplasma blood PCR screening, starting from transplant, is crucial

Risk Factors and Scoring System for Predicting Bacterial Resistance to Cefepime as Used Empirically in Haematology Wards

Objectives. Bacterial resistance is of growing concern in haematology wards. As the inappropriate administration of empirical antibacterial may alter survival, we studied risk factors for resistance to our usual empirical first-line antibacterial therapy, cefepime. Methods. We retrospectively studied 103 first episodes of bacteraemia recorded in our haematology department over 2.5 years. Risk factors for cefepime-resistance were identified by multivariate logistic regression with backward selection (P<0.05). A scoring system for predicting cefepime-resistance was built on independent factor, with an internal validation by the bootstrap resampling technique. Results. 38 (37%) episodes were due to Gram-negative bacteria. Fifty (49%) were due to bacteria resistant to cefepime. Cefepime resistance was significantly associated with a decreased survival at day 30 (P<0.05). Three risk factors were independently associated with cefepime-resistance: acute lymphoblastic leukaemia; ≥18 days since hospital admission; and receipt of any β-lactam in the last month. Patients with ≥2 of these risk factors had a probability of 86% (CI 95%, 25 to 100%) to carry a cefepime-resistant strain. Conclusion. Using our scoring system should reduce the indication of very broad antibacterial regimens in the empirical, first-line treatment of febrile hematology patients in more than 80% of the cases

Allogeneic hematopoietic stem cell transplantation for T-prolymphocytic leukemia: a report from the French society for stem cell transplantation (SFGM-TC)

T-prolymphocytic leukemia (T-PLL), a rare aggressive mature T-cell disorder, remains frequently resistant to conventional chemotherapy. Studies have suggested that allogeneic hematopoietic stem cell transplantation (HSCT) might possibly serve to consolidate the response to initial chemotherapy. The current report summarizes the outcome of 27 T-PLL cases identified in the registry in French Society for stem cell transplantation (SFGM-TC). Prior to HSCT, 14 patients were in complete remission (CR), 10 in partial response, three refractory, or in progression. Following HSCT, 21 patients achieved CR as best response. With a median follow-up for surviving patients of 33 (range, 6–103) months, 10 patients are still alive in continuous CR. Overall survival and progression-free survival estimates at 3 yr were 36% (95% CI: 17–54%) and 26% (95% CI: 14–45%), respectively. The relapse incidence after HSCT was 47% occurring at a median of 11.7 (range, 2–24) months. Overall cumulative incidence of transplant-related mortality was 31% at 3 yr. These results suggest that HSCT may allow long-term survival in patients with T-PLL following induction treatment; however, it is associated with a significant rate of toxicity

Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients

Abstract Background Cytomegalovirus (CMV) infection and disease (CMV episodes) are global concerns after allogeneic hematopoietic stem cell transplantation (HSCT). They affect survival, both by direct and indirect effects. Due to safety issues of current anti-CMV antivirals, long-term CMV prophylaxis is poorly tolerated and the most common strategy to decrease the incidence of CMV disease is preemptive. New, less toxic, molecules are currently being assessed for CMV prophylaxis which should replace or considerably decrease the preemptive approach. The aim of this study was to assess the economic burden of CMV episodes after HSCT with a preemptive approach. Methods We analyzed data from 208 consecutive adults transplanted in our institution, between 2008 and 2013. Hospital resource utilization was retrieved via the linked hospital admissions and Diagnostic Related Groups for the period of conditioning to 12 months after transplant. Results CMV episodes occurred in 70 patients (34%) over the first 12 months following HSCT, after a mean of 75 days (median: 46 (7–334)). The mean total length of stay was significantly associated with the occurrence of a CMV episode (113.9 vs. 87.5 days, p = 0.0002) but was associated neither with the pre-transplant CMV serology of donors/recipients nor with survival. The mean cost of transplant was €104,016 (SD = €37,281) after 12 months. Bivariate and multivariate analyses indicated that the occurrence of >1 CMV episode increased the costs of allogeneic HSCT by 25–30% (p < 0.0001). Conclusion Our study, which is the largest, single-institution cost study of allogeneic HSCT in Europe, shows that two or more CMV episodes significantly increased the transplant cost. New prophylactic strategies to prevent CMV infection and disease should decrease transplant costs