Successful treatment of disseminated fusariosis with posaconazole during neutropenia and subsequent allogeneic hematopoietic stem cell transplantation

We report the case of a 16-year-old girl with acute myelogenous leukemia with disseminated fusariosis, who responded to salvage posaconazole therapy. She subsequently received additional cytotoxic chemotherapy and allogeneic hematopoietic stem cell transplantation with posaconazole continued as secondary prophylaxis. Despite intensive immunosuppressive therapy for graft-versus-host disease, no recrudescence of infection occurred.     

Posaconazole salvage therapy allows successful allogeneic hematopoietic stem cell transplantation in patients with refractory invasive mold infections

We describe the clinical courses of 3 patients with hematologic malignancies (2 with acute myelogenous leukemia and 1 with multiple myeloma) who developed invasive fungal infections due to uncommon molds (Alternaria spp., Paecilomyces lilacinus, and Zygomycetes). Breakthrough invasive fungal infections of the sinus (n=1), lung (n=3), and pericardium (n=1) developed despite fluconazole prophylaxis and failed to respond to treatment with other licensed antifungal therapies, including amphotericin B (n=3), caspofungin (n=2), and voriconazole (n=3), and surgical intervention (n=2). Salvage therapy with posaconazole oral suspension resulted in successful outcomes in all 3 patients, who subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) while on continued posaconazole therapy. The median duration of posaconazole treatment before HSCT was 5 months (range: 1.5-6 months). Posaconazole salvage therapy allowed successful allogeneic HSCT in 3 patients with refractory invasive mold infections.     

BK virus encephalitis with thrombotic microangiopathy in an allogeneic hematopoietic stem cell transplant recipient

R. Lopes da Silva, I. Ferreira, G. Teixeira, D. Cordeiro, M. Mafra, I. Costa, J.M. Bravo Marques, M. Abecasis. BK virus encephalitis with thrombotic microangiopathy in an allogeneic hematopoietic stem cell transplant recipient.
Transpl Infect Dis 2011: 13: 161–167. All rights reserved Abstract: BK virus (BKV) infection occurs most often in immunocompromised hosts, in the setting of renal or bone marrow transplantation. Hemorrhagic cystitis is the commonest manifestation but in recent years infections in other organ systems have been reported. We report an unusual case of biopsy‐proven BKV encephalitis in a hematopoietic stem cell transplant patient who subsequently developed thrombotic microangiopathy. As far as we know, this is the first report of such an association in a transplant patient.     

Disseminated Rhizopus microsporus infection cured by salvage allogeneic hematopoietic stem cell transplantation,antifungal combination therapy,and surgical resection

O. Lebeau, C. Van Delden, J. Garbino, J. Robert, F. Lamoth, J. Passweg, Y. Chalandon. Disseminated Rhizopus microsporus infection cured by salvage allogeneic hematopoietic stem cell transplantation, antifungal combination therapy, and surgical resection.
Transpl Infect Dis 2010: 12: 269–272. All rights reserved Abstract: Invasive Zygomycetes infection complicating prolonged neutropenia is associated with high mortality in the absence of immune recovery. We report a patient who developed disseminated zygomycosis due to Rhizopus microsporus during induction chemotherapy for acute myeloid leukemia. Rescue allogeneic hematopoietic stem cell transplantation (allo‐HSCT) was performed as her only chance of cure of this infection and to treat refractory leukemia. Posaconazole combined with liposomal amphotericin B contained the zygomycosis during prolonged neutropenia due to allo‐HSCT followed by intense immunosuppression for grade IV acute graft‐versus‐host disease. Surgical removal of all infected sites after immune recovery, with prolonged posaconazole treatment, ultimately cured the infection. New combination antifungal therapies might sufficiently control disseminated zygomycosis to allow allo‐HSCT to be performed, assuring life‐saving immune recovery. Surgery appears to be necessary for definite cure of these infections.     

Two cases of hepatic zygomycosis in allogeneic stem cell transplant recipients and review of literature

Gastrointestinal zygomycosis is a rare condition with a high mortality rate. We present 2 fatal cases of hepatic zygomycosis following allogeneic hematopoietic stem cell transplantation and review the literature.     

Non-comparative evaluation of the safety of aerosolized amphotericin B lipid complex in patients undergoing allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at increased risk for invasive fungal infections (IFIs) over prolonged periods of time. Aerosolized amphotericin B lipid complex (ABLC) has shown promise in lung transplant recipients as a convenient means of delivering protective drug to the upper airways avoiding systemic toxicities. The safety and tolerability of aerosolized ABLC in 40 subjects undergoing allogeneic HSCT was prospectively investigated in an open-labeled, non-comparative study. Subjects received aerosolized ABLC treatment once daily for 4 days, then once weekly for 13 weeks; fluconazole was administered daily as standard of care through post-transplant day 100. Pulmonary mechanics were measured before and after each dose of inhaled ABLC; adverse events (AEs) and the development of IFI were also monitored. Cough, nausea, taste disturbance, or vomiting followed 2.2% of 458 total inhaled ABLC administrations; 5.2% of inhaled ABLC administrations were associated with >or=20% decrease in pulmonary function measurements (forced expiratory volume in 1 second or forced vital capacity) and none required treatment with bronchodilators or withdrawal from study. Four mild AEs were considered possibly or probably related to study treatment; no deaths or withdrawals from treatment were attributed to study drug. Of 3 proven IFIs occurring during the study period, only 1, a catheter-related case of disseminated fusariosis, occurred while the subject was receiving study medication. Aerosolized ABLC was well tolerated in allogeneic HSCT recipients. With only 1 of 40 subjects developing IFI while receiving treatment, the combination of fluconazole and inhaled ABLC warrants further study as antifungal prophylaxis following allogeneic HSCT.     

Outcome and risk factors for late-onset complications 24 months beyond allogeneic hematopoietic stem cell transplantation

Objectives: The aim of this retrospective study was to assess the incidence of late complications occurring ≥2 years after allogeneic hematopoietic stem cell transplantation (HSCT) for malignant diseases using a T‐cell depletion strategy. Methods: Between 1984 and 2004, 142 patients were eligible for the study. Total body irradiation (TBI) was carried out in 85% of the patients and T‐cell depletion in 84%. Results: Non‐relapse mortality (NRM) was 3% (95% CI 0–11) at 10 years, and serious late events affected a substantial number of patients. The cumulative incidence (CI) of chronic graft‐versus‐host disease (cGvHD) was 30% (95% CI 23–40), and that of infectious complications was 17% (95% CI 11–23). Multivariate analysis showed a higher risk for late complications in patients with cGvHD (HR 1.9, 95% CI 1.2–3.2, P = 0.011) and patients receiving methylprednisolone during conditioning (HR 1.9, 95% CI 1.1–3.3, P = 0.019 1), patients with cGvHD also having a higher risk for NRM (HR 13.2, 95% CI 1.2–143, P = 0.03), as well as those receiving steroids for >3 months (HR 40.3, 95% CI 2.3–718, P = 0.02) and those receiving antithymocyte globulin (HR 9.6, 95% CI 0.8–68, P = 0.024). Conclusions: A significant proportion of long‐term survivors of HSCT had late complications. cGvHD remained an important risk factor for late complications despite T‐cell depletion resulting in immunosuppression and infectious complications.     

Persistent parvovirus B19 infection resulting in red cell aplasia after allogeneic hematopoietic stem cell transplantation

Persistent parvovirus B19 (PVB) infection has been reported sporadically in immunocompromised patients including hematopoietic stem cell and solid organ transplant recipients. However, the pathogenesis of persistent infection has yet to be fully elucidated. We report here a patient with multiple myeloma developing red cell aplasia during the hematopoietic recovery after allogeneic hematopoietic stem cell transplantation (HSCT) caused by PVB. The patient had already had PVB viremia before transplantation and remained asymptomatic. The route of PVB transmission was considered to be direct contact with the patient's family member with primary PVB infection 1 month before transplantation. Treatment with intravenous immunoglobulin resulted in prompt resolution of anemia. These findings suggest that monitoring of PVB DNA is recommended for patients undergoing HSCT and having contact with individuals with documented PVB infection, even if they are asymptomatic.     

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.     

Conventional versus reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with hematological malignancies

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)-compatible sibling donors is a potential curative treatment for hematological and non-hematological malignancies. Nevertheless, high mortality rates may be associated with this therapy, especially in older patients, those with other comorbidities or who receive a second HSCT. PATIENTS AND METHODS: We analyzed the factors associated with transplant-related mortality (TRM) and overall survival in 157 consecutive adult patients (104 males and 53 females) who received a HSCT [29 bone marrow (BM) transplantation and 128 peripheral blood (PB) transplantation] from a HLA-identical sibling between January 1995 and March 2002 in our institution. One hundred patients received a standard conditioning prior to HSCT (STAND) and 57 patients received a reduced-intensity conditioning (RIC) HSCT. Fifty-eight patients were in an early phase at transplant and 99 in a non-early phase. Median age was 46 yr (16-66), and 90 patients (57%) were >45 yr of age. RESULTS: Patients in the RIC group were older than those in the STAND group, and had a higher proportion of non-early disease phases including a prior autologous HSCT in 39%. Median follow-up for survivors was 28 and 15 months in the STAND and RIC groups (P < 0,001), respectively. Cumulative incidence of TRM at 2 yr was 30% [95% confidence interval (CI) 22-41%] for the STAND group and 22% (95% CI 13-37%) for the RIC group [non-significant (NS)]. Factors associated with a higher TRM in multivariate analysis were: STAND vs. RIC conditioning regimen [relative risk (RR) 5.4; 95% CI 2.3-12.8; P < 0.001]; age > or =45 yr vs. <45 yr (RR 5; 95% CI 2.4-10.8, P < 0.001); second vs. first HSCT (RR 2.8, 95% CI 1.3-6.3, P = 0.01) and non-T-cell-depleted vs. T-cell-depleted graft (RR 2.7, 95% CI 1.3-5.8, P = 0.009). Overall survival (OS) at 2 yr was 52.5 +/- 10.4% for STAND group and 59 +/- 16.8% in RIC group. Factors associated with poorer OS in multivariate analysis were: STAND vs. RIC conditioning regimen (RR 3.4, 95% CI 1.7-6.9, P = 0.001); age > or =45 vs <45 yr (RR 2.5, 95% CI 1.4-4.5, P = 0.002) and diagnosis [other than chronic myeloid leukemia (CML) vs. CML] (RR 2.6, 95% CI 1.2-5.7 P = 0.02). CONCLUSIONS: Our results indicate that the introduction of RIC allogeneic HSCT for patients at high risk for TRM (advanced age, prior HSCT and non-T-cell depletion) leads to a reduction in the TRM and improvement in the OS.     

Roseomonas bacteremia in a recipient of an allogeneic hematopoietic stem cell transplantation

Roseomonas are pink‐pigmented, oxidative, slowly growing, nonfermentative, gram‐negative coccobacilli whose identification may require extensive biochemical testing and molecular profiling. Roseomonas infections vary in severity and clinical presentation, and they predominantly occur in immunocompromised and chronically ill patients. The organism is generally susceptible to carbapenems and aminoglycosides, but resistant to most of the cephalosporins and broad‐spectrum penicillins. Reported here is a patient with lymphoblastic lymphoma who developed Roseomonas mucosa bacteremia after receiving her hematopoietic stem cell allograft. The bacteremic episode was successfully treated with imipenem and amikacin in addition to removal of the central venous catheter. To our knowledge, this is the first report of Roseomonas bacteremia in a stem cell transplantation recipient.     

Low incidence of invasive aspergillosis in allogeneic stem cell transplant recipients receiving amphotericin B inhalation prophylaxis

A. Nihtinen, V.‐J. Anttila, T. Ruutu, E. Juvonen, L. Volin. Low incidence of invasive aspergillosis in allogeneic stem cell transplant recipients receiving amphotericin B inhalation prophylaxis.
Transpl Infect Dis 2011. All rights reserved Abstract: In this retrospective study we evaluated the impact of amphotericin B (AmB) deoxycholate inhalation prophylaxis on invasive aspergillosis (IA) in 611 allogeneic stem cell transplant (alloSCT) recipients and their tolerance of the inhalations. The inhalations were not used in 1996–2000 (Period I). In 2001–2005 (Period II) all patients with acute graft‐versus‐host disease treated with high‐dose methylprednisolone used the inhalation prophylaxis with a dose of 25 mg daily. No systemic antifungal prophylaxis was routinely used during the study period. IA was detected in 17 (13 proven, 4 probable) out of 257 (6.6%) patients transplanted in Period I and in 9 (6 proven, 3 probable) out of 354 (2.5%) patients transplanted in Period II (P=0.007). The median time to the diagnosis of IA was 95 days and 155 days post transplant in the 2 periods (P=0.225). The mortality of the patients with IA was 94.1% and 66.6% in Period I and Period II. The median duration of AmB inhalation prophylaxis was 84 days. Breakthrough IA was detected in 1 of the 111 (1%) patients during the prophylaxis. No discontinuation of prophylaxis due to side effects was recorded. Overall, with a median follow‐up of 3.5 and 4.6 years, 42.4% and 59% of the patients were alive in Period I and Period II, respectively (P=0.001). In conclusion, the incidence of IA fell during the AmB inhalation prophylaxis, and the inhalations were well tolerated. Mortality of patients with IA was high. The overall survival of patients was significantly higher in Period II, indicating the advances made in SCT therapy over the 10‐year period.     

Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients

We report on bloodstream infection (BSI) rates, risk factors, and outcome in a cohort of 298 adult and pediatric hematopoietic stem cell transplantation (HSCT) recipients at Memorial Sloan-Kettering Hospital from September 1999 through June 2003. Methods. Prospective surveillance study. BSI rates are reported per 10,000 HSCT days. Date of engraftment is defined as the first of at least 3 consecutive dates of absolute neutrophil count >500/mm(3) after stem cell infusion. BSI severity grades: severe (intravenous antibiotics), life threatening (sepsis), or fatal (caused or contributed to death). Results. The incidence of pre- and post-engraftment BSI was 22% and 19.5%, respectively. Pre-engraftment highest rates were observed for viridans streptococci (58), Enterobacteriaceae (39), and Enterococcus faecium (34). Post-engraftment rates ranged from 0.2 to 2.9 without any predominant pathogen. In multivariate analyses, pre-engraftment BSI was associated with diagnosis of chronic myelogenous leukemia, age >18 years and peripheral blood stem cell graft; post-engraftment BSI was associated with acute graft-versus-host disease, neutropenia, and liver or kidney dysfunction. Attributable mortality was 12.5% and 1.7% for pre- and post-engraftment BSI, respectively. BSI fatality rates were 24% for viridans streptococci, 8% for E. faecium, 11% for Staphylococcus aureus, and 67% for Candida. Conclusions. Pre-engraftment BSI, especially by viridans streptococci and E. faecium, was associated with substantial attributable mortality. Post-engraftment BSI was a marker of post-transplant complications and rarely the primary cause of death.     

异基因造血干细胞移植后早期结核分枝杆菌感染

目的:分析异基因造血干细胞移植后早期结核分枝杆菌感染的患病率、临床特征、诊断、治疗及预后.方法:对我院连续接受异基因造血干细胞移植的258例患者中确诊为结核分枝杆菌感染的6例患者进行回顾性分析及总结.结果:结核病的发生率为2.32%(6/258),在单倍型、非血缘、同胞相合移植3种不同移植方式中发生率分别为1.90%、...     

Physical activity for patients undergoing an allogeneic hematopoietic stem cell transplantation: benefits of a moderate exercise intervention

An allogeneic hematopoietic stem cell transplantation (HSCT) can have profound and lasting adverse effects on a patient’s physical and psychological well‐being. So far, only few studies have investigated the effectiveness of physical activity over the entire inpatient phase of an allogeneic HSCT. Purpose: We performed a randomized controlled study to examine the influence of a controlled moderate exercise program starting parallel to chemotherapeutic conditioning and total body irradiation on the patient’s physical and psychological constitution. Patients and methods: Forty‐seven patients undergoing an allogeneic HSCT were randomly assigned to an exercise group (EG) or a control group (CG). While the EG took part in an endurance and activity of daily living‐training twice a day, the CG received the clinic’s standard physiotherapy program once a day. Results: Significant differences and/or trends in favor of the EG were observed regarding the primary endpoint endurance performance (P = 0.002), muscular strength (P = 0.022), fatigue (P = 0.046), and emotional state (P = 0.028) without posing an additional risk for the individual. Conclusion: The results show that the training program is feasible and seems to have positive influences on physical performance and quality of life in patients undergoing an allogeneic HSCT. However, further studies are necessary to confirm these results.     

异基因造血干细胞移植后并发肺孢子菌肺炎的临床观察

目的:探讨异基因造血干细胞移植后合并肺孢子菌肺炎(PCP)的临床诊断、治疗和预防措施.方法:回顾分析9例造血干细胞移植后临床诊断为PCP的表现、肺部CT影像、血气分析、G试验、支气管镜检查等相关资料,进行总结.结果:9例患者临床诊断PCP的时间在移植+80～+316 d,早期表现为发热、咳嗽、进行性呼吸困难等非特异性症...     

Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: a retrospective I-BFM analysis of 333 children

Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four-year probability of overall survival (4y-pOS) was 14%. 4y-pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001). Achievement of a subsequent remission impacted survival (P = <0·0001). For patients receiving a second transplant survival with or without achieving a subsequent remission was comparable. Graft source (bone marrow vs. peripheral blood stem cells, P = 0·046) and donor choice (matched family vs. matched unrelated donor, P = 0·029) positively impacted survival after relapse. Disease recurrence and non-relapse mortality at four years reached 45% and 22%.