Retrospective cohort analysis comparing the incidence of deep vein thromboses between peripherally-inserted and long-term skin tunneled venous catheters in hemato-oncology patients.

BACKGROUND: The introduction of central venous catheters has advanced medical care, particularly in hemato-oncology. However these can be associated with an increased thrombotic risk. Previous studies have compared the rate of thrombotic events between peripherally- inserted (PICCs) and long term skin tunneled catheters (LTSTCs) noting fewer complications associated with the latter, though this has rarely translated into clinical practice. The objectives of our study was to compare the cumulative incidence of thrombotic events between peripherally-inserted and long term skin tunneled venous catheters. PATIENTS/METHODS: We performed a retrospective, single center cohort analysis of patients with hematological malignancies who had either a PICC or LTSTC line inserted between January 2010 through January 2013. Cumulative incidences of thrombotic events were compared between the two groups, and post-thrombotic complications were also examined. RESULTS: 346 patients had a PICC inserted with cumulative incidence of symptomatic thrombosis of 5.8%, while 237 patients had a LTSTC inserted with a cumulative incidence of 1.7% (p = 0.003). Post-thrombotic complication rates, particularly infection, were higher in the PICC group compared to the LTSTC group (p = 0.597). CONCLUSIONS: Our study showed that the incidence of thrombotic events in hemato-oncology patients was significantly lower in those who had a LTSTC compared to PICC line. As the use of central venous lines increases in hemato-oncology patient care, a randomized trial comparing PICCs and LTSTCs is necessary to address which venous access is most appropriate in this cohort of patients, with minimal risk of morbidity and mortality.

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.

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

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.

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.

The feasibility of plerixafor as a second-line stem cell mobilizing agent in children.

In patients heavily pretreated with myelosuppressive chemotherapy or irradiation, Granulocyte colony stimulating factor (G-CSF) may fail to mobilize stem cells from the bone marrow. Plerixafor is emerging as a reliable alternate option in such situations in adult patients. Robust data in support of the high efficacy and safety of plerixafor are available in adults. Very little evidence is available on the usefulness of this drug among children. We report our experience with plerixafor usage on 5 occasions in pediatric patients, with a success rate of 60%. No significant side effects were encountered in any patient.

Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission.

BACKGROUND: Approximately 40% of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia achieve long-term survival following unrelated donor hematopoietic stem cell transplantation in first complete remission but severe graft-versus-host disease remains a problem affecting survival. Although T-cell depletion abrogates graft-versus-host disease, the impact on disease-free survival in acute lymphoblastic leukemia is not known. DESIGN AND METHODS: We analyzed the outcome of 48 adults (median age 26 years) with high-risk, Philadelphia-chromosome-negative acute lymphoblastic leukemia undergoing T-cell depleted unrelated donor-hematopoietic stem cell transplantation (67% 10 of 10 loci matched) in first complete remission reported to the British Society of Blood and Marrow Transplantation Registry from 1993 to 2005. RESULTS: T-cell depletion was carried out by in vivo alemtuzumab administration. Additional, ex vivo T-cell depletion was performed in 21% of patients. Overall survival, disease-free survival and non-relapse mortality rates at 5 years were 61% (95% CI 46-75), 59% (95% CI 45-74) and 13% (95% CI 3-25), respectively. The incidences of grades II-IV and III-IV acute graft-versus-host disease were 27% (95% CI 16-44) and 10% (95% CI 4-25), respectively. The actuarial estimate of extensive chronic graft-versus-host disease at 5 years was 22% (95%CI 13-38). High-risk cytogenetics at diagnosis was associated with a lower 5-year overall survival (47% (95% CI 27-71) vs. 68% (95% CI 44-84), p=0.045). CONCLUSIONS: T-cell depleted hematopoietic stem cell transplantation from unrelated donors can result in good overall survival and low non-relapse mortality for adults with high-risk acute lymphoblastic leukemia in first complete remission and merits prospective evaluation.

Relapse of primitive mediastinal lymphoma as a myeloid mass following beam autologous transplant and subsequent refractoriness to matched unrelated umbilical cord blood allograft.

Outlining the treatment for an unclassifiable lymphoid malignancy is often difficult. A highly undifferentiated lymphomatous mass that relapsed in spite of intense chemotherapy and autologous transplant is reported. At relapse, there was differentiation into myeloid lineage. Though remission was achieved with AML-type reinduction chemotherapy, the mass recurred post allogenic cord blood stem cell transplant.

The impact of extramedullary disease at presentation on the outcome of myeloma.

This study was conducted to compare the presenting features and outcome of newly-diagnosed myeloma with and without extramedullary (EM) manifestations and to determine the optimum treatment. Seventy-five (16.3%) patients with EM involvement at diagnosis were compared with 384 cases without EM disease. EM patients had a more favourable International Staging System and a different distribution of myeloma isotypes. When adjusted according to the independent risk factors, patients in the EM group treated with chemotherapy alone had significantly shorter overall survival (OS) compared to those without EM disease receiving similar treatment. High-dose treatment (HDT) was associated with significantly improved OS in both groups; however, it had more impact on OS among EM group, overcoming the negative prognostic impact of presenting EM disease. Patients in the EM group treated with HDT have a similar outcome to those without EM manifestations treated with HDT. HDT should form an integral component of first-line treatment for patients with EM disease whenever possible.

Familial T-cell non-Hodgkin lymphoma caused by biallelic MSH2 mutations.

Familial non-Hodgkin lymphoma (NHL) is rare and in most cases, no underlying cause is identifiable. We report homozygous truncating mutations in the mismatch repair gene MSH2 (226C-->T; Q76X) in three siblings who each developed T-cell NHL in early childhood. All three children had hyperpigmented and hypopigmented skin lesions. Constitutional biallelic MSH2 mutations have previously been reported in five individuals, all of whom developed malignancy in childhood. Familial lymphoma has not been reported in this context or in association with biallelic mutations in the other mismatch repair genes MLH1, MSH6 or PMS2. In addition, hypopigmented skin lesions have not previously been reported in biallelic MSH2 carriers. Our findings therefore expand the spectrum of phenotypes associated with biallelic MSH2 mutations and identify a new cause of familial lymphoma. Moreover, the diagnosis has important management implications as it allows the avoidance of chemotherapeutic agents likely to be ineffective and mutagenic in the proband, and the provision of cascade genetic testing and tumour screening for relatives.

Histologic features of the liver biopsy predict the clinical outcome for patients with graft-versus-host disease of the liver.

We reviewed liver histologic results from all allogeneic hematopoietic stem cell transplant recipients from our institution with a confirmed diagnosis of liver graft-versus-host disease (L-GVHD), no concomitant causes of liver dysfunction, and at least 1 diagnostic liver biopsy sample (n=33) to ascertain whether histologic features predicted clinical outcome. The 1-year probability of nonrelapse mortality (NRM) from the onset of liver dysfunction was 68.15%, with a median overall survival (OS) of 6.2 months for the entire group. Histologic features traditionally linked to the diagnosis of L-GVHD (eg, bile duct damage, bile duct lymphocytic infiltration, portal inflammation, and ductopenia) had no association with patient outcome. However, an extended histologic analysis showed that a high level of lobular inflammation (LI) and a low level of hepatocyte ballooning (HB) were independent favorable prognostic factors for NRM (RR, 5.14; P=.033; and relative risk (RR), 0.18; P=.018, respectively) and OS (RR, 3.99; P=.032; and RR, 0.23; P=.037, respectively). The presence and severity of LI and HB were not associated with patient- or transplant-related characteristics or L-GVHD clinical factors such as timing of the biopsy from the onset of L-GVHD, acute versus chronic presentation, or whether the patients had started immunosuppressive treatment with steroids at the time of the biopsy. In multivariate analysis that included clinical prognostic factors, the combined histologic risk posed by high LI and low HB retained independent favorable prognostic value for NRM (RR, 5.05; P=.015) and OS (RR, 3.31; P=.038). This information, if replicated in other studies, could expand current indications for liver biopsy in patients with L-GVHD, not only to exclude other causes of liver injury, but also to predict clinical outcome, and should be considered in the selection of patients and the design of future trials with new experimental therapies for this complication. Prospective validation of our findings is warranted.