Unell Riley

High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukemia resistant to fludarabine therapy.

The combination of high dose methylprednisolone and rituximab induces superior overall (93%) and complete (14%) response rates compared to high dose methylprednisolone alone (overall 43%, complete remission 0%) in heavily pre-treated chronic lymphocytic leukemia patients with advanced disease. Despite its efficacy the combination is not easily manageable because of the high rate of opportunistic infections.

An early CT-diagnosis-based treatment strategy for invasive fungal infection in allogeneic transplant recipients using caspofungin first line: an effective strategy with low mortality

Empirical antifungal therapy is frequently used in allogeneic transplant patients who have persistent febrile neutropenia and can be associated with high cost, toxicity and breakthrough infections. There are limited reports of strategies for early diagnosis of invasive fungal infection (IFI) and, to our knowledge, no reports of treatment strategies based only on high-resolution computerized tomography (HRCT) scans. We used an early treatment strategy for IFI in 99 consecutive patients undergoing allogeneic transplantation. Patients received caspofungin if they had antibiotic-resistant neutropenic fever for more than 72 h and a positive HRCT scan. Fifty-three of 99 patients (54%) had antibiotic-resistant neutropenic fever at 72 h and would have received parenteral antifungal treatment if an empirical approach had been used. The HRCT-based strategy reduced the use of parenteral antifungal agents to 17/99 patients (17%), a 68% reduction. No subsequent diagnoses of IFI occurred within 100 days in patients with a negative HRCT. Only one patient died from IFI within 100 days. These data suggest that this non-empirical strategy may be feasible and that caspofungin may be effective in this setting. A randomized controlled trial is warranted to further assess these results.

Antimicrobial Prophylaxis to Prevent Opportunistic Infections in Patients with Chronic Lymphocytic Leukemia after Allogeneic Blood or Marrow Transplantation

Opportunistic infections have been a problem after BMT in CLL. We have allografted seven patients with B-CLL (n = 6) or B-prolymphocytic leukemia (n = 1) from matched siblings (n = 6) or a mismatched unrelated donor (n = 1). Amongst the first six, we saw two cases of recurrent or prolonged cytomegaloviremia and CMV disease, one listeria meningitis, and one fatal toxoplasma encephalitis. The latter two developed in the setting of steroid therapy of GVHD with extensive prior fludarabine therapy. Prophylaxis for opportunistic infections was developed on an ongoing basis as new infectious complications were seen. The current drug prophylaxis, which has been successful for eight months in the last patient despite pretreatment with fludarabine and steroid therapy for GVHD, is directed against pneumocystis, toxoplasma, fungi, and pneumococci. It includes immunoglobulin (for 3 1/2 months), pyrimethamine-sulfadiazine (for 4 months and during steroids), fluconazole (for 2 1/2 months), cotrimoxazole or pentamidine (for 2 years) and penicillin (lifelong). Dietary precautions are followed for 4 months and during steroids to prevent listeriosis. Four patients are alive in remission with no active infectious problems 8-44 months (median 29) after BMT. We recommend adoption of these or similar prophylactic measures for BMT in CLL as a baseline which can be modified if new infections are identified and according to individual needs.

High readmission rates are associated with a significant economic burden and poor outcome in patients with grade III/IV acute GvHD

Graft‐versus‐host disease (GvHD) is a common complication following haematopoietic stem cell transplant but little is published about the impact of this condition on hospital readmission rates. We report a retrospective analysis of readmission rates and associated costs in 187 consecutive allogeneic transplant patients to assess the impact of GvHD. The overall readmission rate was higher in patients with GvHD (86% (101/118) vs. 59% (41/69), p < 0.001). The readmission rate was higher both in the first 100 d from transplant (p = 0.02) and in the first year following transplant (p < 0.001). 151/455 (33%) of all readmission episodes occurred within 100 d of transplant. The mean number of inpatient days was significantly higher in patients with grade III/IV acute GvHD (101 d) compared with those with grade I/II GvHD (70 d; p = 0.003). The mean cost of readmission was higher in patients with GvHD (£28 860) than in non‐GvHD patients (£13 405; p = 0.002) and in patients with grade III/IV GvHD (£40 012) compared with those patients with grade I/II GvHD (£24 560; p = 0.038). Survival was higher in those with grade I/II GvHD (55%) compared to grade III/IV GvHD (14%; p < 0.001). This study shows the high economic burden and poor overall survival associated with grade III/IV GvHD.

First report of fatal human infections with the cactophilic yeast Sporopachydermia cereana

Sporopachydermia cereana is a cactophilic yeast, which is not recognised as a human pathogen. We describe two fatal infections with this fungus in profoundly neutropenic patients. S. cereana escapes detection by conventional mycological identification methods. This organism may be an under-recognised cause of fatal fungal sepsis among immunocompromised patients.

Clinical profile and outcome of urotheliotropic viral haemorrhagic cystitis following haematopoietic stem cell transplantation: a 7-year tertiary centre analysis

Abstract Viral haemorrhagic cystitis (HC) is a significant complication after haematopoietic stem cell transplantation (HSCT), with a potential for major morbidity. The aim of this 7-year analysis of 1160 HSCT patients was to evaluate risk factors for the incidence, severity, toxicity of therapy, clinical course, and outcome of this condition. The overall incidence of HC was 5·8%, with most cases occurring after allogeneic HSCT. Unrelated donors (P = 0·001), non-peripheral blood stem cell source (P = 0·005), myeloablative conditioning (P<0·001), use of alemtuzumab in conditioning (P = 0·001), and severe acute graft versus host disease (P<0·001) were independent risk factors for an increased incidence of HC post-allogeneic transplant on multivariate analysis. Severe forms of HC were associated with grades II–IV acute graft versus host disease and a longer duration of haematuria. Contrary to previous studies which were carried out on smaller patient populations, busulphan, cyclophosphamide, anti-thymocyte globulin, and total body irradiation were not found to independently increase the risk of viral HC, unless used in a myeloablative combination. Neither duration of viriuria nor peak viral load in urine influenced the severity of HC on multivariate analysis. Severe HC contributed to the deaths of two patients. Overall survival was not statistically different between patient subgroups with non-severe and severe HC.

An early computed tomography-guided antifungal treatment strategy is safe and efficacious in patients undergoing chemotherapy for high-risk acute leukemia

We read with interest the recent review by Ruping et al. [1] on the prevention and treatment of invasive fungal infections (IFIs) in patients with leukemia. The Royal Marsden NHS Foundation Trust is a large cancer center in south London, treating patients with high-risk acute leukemia (AL) with intensive chemotherapy and allogeneic transplant. In January 2006, we instituted an early treatment strategy for IFIs based on computed tomography (CT) criteria rather than empirical therapy. Patients underwent high-resolution CT (HRCT) of the thorax (1.25 mm sections at intervals of 10 mm) after 72 h of persistent antibiotic-resistant neutropenic fever. Patients with a positive HRCT (based on major changes: cavitation, air-crescent sign, and halo sign; or minor changes: nodules and new infiltrates) commenced liposomal amphotericin B (3 mg/kg once daily). Patients with a negative CT scan continued itraconazole prophylaxis. We had previously found this to be a feasible approach in patients undergoing allogeneic transplant [2]. Here we present results from a recent audit of 151 adult patients, treated between 2006 and 2009, with intensive chemotherapy for AL in our unit. The study was approved by the clinical audit committee and patients had given informed consent. Prophylaxis with itraconazole was used in patients with acute myeloid leukemia and fluconazole in those with acute lymphoblastic leukemia. Of 151 patients identified, 62% had a persistent fever, of whom 78% had HRCT performed at 72 h. Fifty-five percent of patients had a positive scan and 45% had a negative scan. All patients with positive HRCT had antifungals commenced according to the policy. In addition, antifungal therapy was commenced in three patients with negative HRCT, and six patients with no HRCT, due to clinical symptoms and/or positive laboratory tests, and in two patients empirically during an intensive care unit admission. Thus, approximately half the patients with ongoing temperatures did not require antifungal treatment. Importantly, in this group there were no breakthrough infections or deaths due to fungal infection within 100 days. This represented a significant cost saving, and reduced toxicity to the patient from additional agents, without compromising their clinical outcome. In the group who received antifungal treatment, responses to therapy were excellent, with only two deaths directly related to IFIs (Aspergillus fumigatus, Candida dubliniensis)—both in patients with refractory leukemia. In conclusion, we believe this to be a safe and efficacious strategy for patients with AL. In line with recommendations made in a recent review by Leventakos et al. [3], we agree that an individualized patient approach within the overall strategy is critical, in particular the need to carefully correlate the HRCT findings with clinical and laboratory