Christèle Ferry

Epstein-Barr virus (EBV) reactivation in allogeneic stem-cell transplantation: relationship between viral load, EBV-specific T-cell reconstitution and rituximab therapy.

Background. Monitoring of Epstein-Barr virus (EBV) reactivation after allogeneic hematopoietic stem-cell transplantation markedly improved with quantitative real-time polymerase chain reaction amplification of EBV DNA and visualization of EBV-specific CD8+ T cells with peptide-human leukocyte antigen (HLA) class I tetramers. We decided to combine these methods to evaluate posttransplant EBV reactivation and rituximab therapy. Methods. We followed 56 patients treated with an HLA-genoidentical sibling (n=32), an HLA-matched unrelated donor (MUD, n=19), or an unrelated cord-blood transplant (n=5). EBV DNA was quantified in plasma and in peripheral blood mononuclear cells (PBMC). Patient CD8+ T cells were stained with a panel of eight tetramers. Results. EBV DNA was detected in half of the patients, mainly in the MUD group (17/19). In 19 patients, viral DNA was detected only in the cellular compartment. All patients who controlled reactivation without rituximab and despite a viral load of greater than 500 genome equivalents (gEq)/150,000 PBMC mounted an EBV-specific CD8+ T-cell response in greater than 1.4% of CD3+CD8+ T cells. Plasmatic EBV genome was found in nine patients preceded by a high cellular viral load. Three of these patients controlled the reactivation before or without the introduction of rituximab, and they all developed a significant and increasing EBV-specific T-cell response. Patients with EBV-specific T cells at the onset of reactivation controlled viral reactivation without rituximab. Conclusion. This study emphasizes the benefit of an early and close monitoring of EBV reactivation and CD8+-specific immune responses to initiate rituximab only when necessary and before the immune response becomes overwhelmed by the viral burden.

Disseminated adenovirus infections after allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcome

We analyzed the factors and outcome of patients with disseminated adenovirus infection (dAdV) after allogeneic hematopoeitic stem cell transplantation (HSCT). Thirty patients with dAdV were identified among 620 allogeneic HSCT recipients. Primary diseases were leukemia (n=17), Fanconi anemia (n=12) or others (n=1). Source of stem cells was unrelated in 28 and related in 2 patients. The graft consisted of peripheral blood (n=3), bone marrow (n=12) and unrelated cord-blood (UCB, n=15). Risk factors for dAdV in unrelated HSCT recipients were previous Fanconi disease (p=0.03) and GVHD (p=0.02) in children, and cord blood source of stem cells (p=0.029) and GVHD (0.024) in adults.

Breakthrough Disseminated Aspergillus ustus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients Receiving Voriconazole or Caspofungin Prophylaxis

ABSTRACT Aspergillus ustus is an uncommon clinical species which is poorly susceptible to antifungals. We report two cases of A. ustus infections that occurred in allogeneic stem cell transplant recipients while they were receiving either voriconazole or caspofungin. Prolonged use of these new antifungal agents may increase the risk of the emergence of resistant organisms.

Palivizumab Treatment of Respiratory Syncytial Virus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Among 40 allogeneic stem cell transplant recipients who developed symptomatic respiratory syncytial virus infection, including 22 patients with lower respiratory tract infection, 19 received palivizumab (9 of whom had upper respiratory tract disease). Palivizumab did not prevent progression to lower respiratory infection and had no impact on the overall survival rate.

Outcomes, infections, and immune reconstitution after double cord blood transplantation in patients with high-risk hematological diseases.

A. Ruggeri, R. Peffault de Latour, M. Carmagnat, E. Clave, C. Douay, J. Larghero, J.‐M. Cayuela, R. Traineau, M. Robin, A. Madureira, P. Ribaud, C. Ferry, A. Devergie, D. Purtill, C. Rabian, E. Gluckman, A. Toubert, G. Socié, V. Rocha. Outcomes, infections, and immune reconstitution after double cord blood transplantation in patients with high‐risk hematological diseases
Transpl Infect Dis 2011: 13: 456–465. All rights reserved

Impact of comorbidity indexes on non-relapse mortality

Comorbidity indexes (CI) have been reported to predict non-relapse mortality (NRM) and overall survival after allogeneic hematopoietic stem cell transplantation (HSCT) (Charlsons comorbidity index (CCI), hematopoietic cell transplantation CI (HCT-CI) and the pre-transplantation assessment of mortality (PAM) score). Which of these indexes best predict survival is unknown yet. We retrospectively studied 286 patients who underwent allogeneic HSCT. HCT-CI and PAM scores required grading according to pre-transplant pulmonary function tests (PFTs), which were lacking for some patients. We thus designed a reduced HCT-CI and an adjusted PAM, without results of PFTs. Using CCI, 25% of patients had indexes of 1 or more; median reduced HCT-CI score was 1; median adjusted PAM score was 24. The discriminative properties of the three CIs were rather low in our population. Comparison of patients and transplant characteristics between our and Seattle groups cohorts, however, revealed significant differences in more children, in more cord blood HSCT and in HSCT for Fanconi anemia in St Louis. Finally, multivariate analysis of scoring items revealed that age, matched unrelated or mismatched donor and hepatic disease were associated with NRM in our cohort. Translating use for patients counseling or decision to proceed to transplant of these CIs will need prospective studies in a large independent cohort.

Double cord blood transplantation in patients with high risk bone marrow failure syndromes

Patients with bone marrow failure syndromes (BMFS) who reject a first allogeneic transplant or fail immunosuppressive therapy (IST) have an especially grim prognosis. We report 14 patients (eight adults, six children) transplanted with double cord blood transplantation (dUCBT) for BMFS. Neutrophil recovery was observed in eight patients, with full donor chimerism of one unit, and acute GVHD in 10. With a median follow‐up of 23 months, the estimated 2 years overall survival was 80 ± 17% and 33 ± 16% for patients with acquired and inherited BMFS, respectively. Transplantation of two partially HLA‐matched UCB thus enables salvage treatment of high‐risk patients with BMFS.

Influence of bone marrow graft B lymphocyte subsets on outcome after HLA‐identical sibling transplants

The potential role of the infused B cell subset after Hematopoietic Stem Cell Transplantation has not been yet studied. The present study analyzed the impact of B cells on transplant outcome in 254 patients who received a bone marrow graft from a human leucocyte antigen‐identical sibling donor. The influence of B lineage‐specific hematopoietic progenitor cells (CD34+ CD19+) and B cells (immature and mature B cells, CD34− CD19+) was also analyzed. All included patients received a myeloablative regimen. The cumulative incidence function of acute graft‐versus‐host (GvHD) grade II to IV was 48% and was inversely associated with the number of CD34+ CD19+. There were no statistically significant associations between B cell subsets and chronic GvHD or survival. The CD34+ CD19+ B cell subset remained significantly associated with acute GvHD in multivariate analysis (Relative risk = 0·32, 95% confidence interval: 0·11–0·92, P = 0·035). In conclusion, a higher B lineage‐specific hematopoietic progenitor cells (CD34+ CD19+) cell dose is associated with a significant decrease incidence of acute GvHD.

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.

Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks

Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23–230) and 8.6×108 (range 0.7–75×108), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units.