Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group.

The aim of this work is to produce recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles released from 1999 to 2015 (January) was used as a source of scientific evidence. Recommendations were produced using a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet and European Blood and Marrow Transplantation Group. Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention and management of relapse after transplant. Patients with intermediate-2- or high-risk disease and age <70 years should be considered as candidates for allo-SCT. Patients with intermediate-1-risk disease and age <65 years should be considered as candidates if they present with either refractory, transfusion-dependent anemia, or a percentage of blasts in peripheral blood (PB) >2%, or adverse cytogenetics. Pre-transplant splenectomy should be decided on a case by case basis. Patients with intermediate-2- or high-risk disease lacking an human leukocyte antigen (HLA)-matched sibling or unrelated donor, should be enrolled in a protocol using HLA non-identical donors. PB was considered the most appropriate source of hematopoietic stem cells for HLA-matched sibling and unrelated donor transplants. The optimal intensity of the conditioning regimen still needs to be defined. Strategies such as discontinuation of immune-suppressive drugs, donor lymphocyte infusion or both were deemed appropriate to avoid clinical relapse. In conclusion, we provided consensus-based recommendations aimed to optimize allo-SCT in PMF. Unmet clinical needs were highlighted.

Umbilical cord blood graft engineering: challenges and opportunities.

We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specific T-cells or chimeric-antigen receptor T-cells which are reviewed in this study.

Adenoviral infections in adult allogeneic hematopoietic SCT recipients: a single center experience.

Disseminated adenoviral infection (AI) is associated with profound immunosuppression and poor outcome after allogeneic hematopoietic SCT (allo-HSCT). A better understanding of AI in allo-HSCT recipients can serve as a basis to develop more effective management strategies. We evaluated all adult patients who received allo-HSCT at MD Anderson Cancer Center between 1999 and 2008. Among the 2879 allo-HSCT patients, 73 (2.5%) were diagnosed with AI. Enteritis (26%) and pneumonia (24%) were the most common clinical manifestations; pneumonia was the most common cause of adenovirus-associated death. A multivariable Bayesian logistic regression showed that when the joint effects of all covariates were accounted for, cord blood transplant, absolute lymphocyte count (ALC) ≤ 200/mm(3) and male gender were associated with a higher probability of disseminated AI. The OS was significantly worse for patients with AI that was disseminated rather than localized (median of 5 months vs median of 28 months, P<0.001) and for patients with ALC ≤ 200/mm(3) (P<0.001). Disseminated AI, in patients who received allo-HSCT, is a significant cause of morbidity and mortality. Strategies for early diagnosis and intervention are essential, especially for high-risk patients.

Outcomes of second allogeneic hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia.

For patients with ALL who relapse following allo-SCT, only a second SCT provides a realistic chance for long-term disease remission. We retrospectively analyzed the outcomes of 31 patients with relapsed ALL after a prior allo-SCT, who received a second SCT (SCT2) at our center. With a median follow-up of 3 years, 1- and 3-year PFS was 23 and 11% and 1- and 3 year OS rates were 23 and 11%. Twelve patients (39%) were transplanted with active disease, of whom 75% attained a CR. We found a significant relationship between the time to treatment failure following first allograft (SCT1) and PFS following SCT2 (P=0.02, hazard ratio=0.93/month). In summary, a second transplant remains a potential treatment option for achieving response in a highly refractory patient population. While long-term survival is limited, a significant proportion of patients remains disease-free for up to 1 year following SCT2, providing a window of time to administer preventive interventions. Notably, our four long-term survivors received novel therapies with their second transplant underscoring the need for a fundamental change in the methods for SCT2 to improve outcome.

Acute Campylobacter jejuni enteritis in 385 hospitalised patients.

Twenty healthy controls and 385 adult patients suffering from acute enteritis or gastroenteritis were enrolled for the study of Campylobacter Jejuni infection over a period of 2 years. Thirty five stool samples showed C jejuni on stool culture. The isolation rates were at peak in the monsoon season and from watery and bloody stool specimens. Pure C jejuni culture was obtained in 18 of 35 samples; the other 17 samples showed polymicrobial infection or infestation. Nine of 35 patients were treated with erythromycin 1 g in divided doses for 7 days. Repeat stool cultures did not grow C jejuni. There was no resistance to erythromycin therapy. C jejuni are fastidious organisms and require special medium and microaerophilic environment for culture.

Association of peptic ulcer with Helicobacter pylori and the recurrence rate. A three year follow-up study.

Helicobacter pylori is associated with 70-100% of peptic ulcers. Relapse of infection has been shown to cause recurrences of ulcers in a large number of studies. We diagnosed 137 cases of peptic ulcer (121 DU; 16 GU) during a 3 year period. Of these, 117 were positive for H pylori. Sixty six of the 117 cases staying in the vicinity of the Hospital were followed up for a minimum period of 3 months upto a maximum period of 3 years. In 91 examinations there was relapse of H pylori infection and ulcer recurrence was seen in 58 (63%), whereas ulcer recurred only in 6 out of 61 examinations where H pylori had not relapsed (10%). The difference was highly significant by Chi square test. (P less than 0.001).

Relapse of Helicobacter pylori infection after different treatment regimens. A 3-month follow-up study.

Helicobacter pylori infection of gastric antrum is associated with a majority of cases of peptic ulcer (70-100%). Studies have shown that when this organism is eradicated, the recurrence of ulcer falls to less than one-third of those in whom the infection persists or relapses. Monotherapy with bismuth salts, tinidazone or amoxycillin has been shown to result in early relapse and recurrence of ulcers. However, dual or triple therapy regimens are more effective. We conducted a randomised controlled study using tripotassium dicitrato bismuthate (TDB) (10 patients); amoxycillin (combined with ranitidine for ulcer healing) (9 patients) and dual therapy with both amoxycillin and TDB (10 patients). Our study showed that relapse rates at the end of 3 months was significantly less if dual therapy with TDB and amoxycillin is used as compared to TDB alone (p less than 0.05).