Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

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.

Proceedings from the 1st Insights in Hematology Symposium, Cluj-Napoca, Romania March 11-12, 2016.

In the March 2016 issue of the Lancet Haematology, the editorial office published a paper stating the roadmap for European research in hematology, based on the European Hematology Association (EHA) consensus document that outlines the directions in hematology for the following years across the continent. The meeting entitled "Insights in hematology" is organized a support for the initiative of a roadmap for European hematologists regarding research, may it be basic research or clinical research, but this consensus should not be focused mainly on European institutions, but rather form the backbone of global research between Europe and the United States, Japan or any other country. This will allow Europeans to learn as well as to share their experience with the rest of the scientific and medical community. And the Cluj-Napoca meeting should be followed by other such meetings all across the EU.

First Successful Haploidentical Stem Cell Transplantation in Romania.

Hematopoietic stem cell transplantation is an established treatment for many malignant and non-malignant haematological disorders. In the current case report, we describe the first haploidentical stem cell transplantation, used for the first time in Romania, the case of a 33 year-old young woman diagnosed with Hodgkin's lymphoma that has underwent a haploSCT after she relapsed from several chemotherapy regimens, as well as after an autologous stem cell transplantation. This success represents a prèmiere in Romanian clinical hematology, being the first case of a haploSCT in Romania, as well as in South-Eastern Europe.

Allogeneic stem-cell transplantation in patients with cutaneous lymphoma: updated results from a single institution.

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) and its common variants mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are rare extranodal non-Hodgkin's lymphomas. Patients who present with advanced disease and large-cell transformation (LCT) are incurable with standard treatments. In this article, we report the largest single-center experience with allogeneic stem-cell transplantation (SCT) for advanced CTCL. PATIENTS AND METHODS: This is a prospective case series of 47 CTCL patients who underwent allogeneic SCT after failure of standard therapy between July 2001 and September 2013. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) curves. The method of Fine and Gray was used to fit regression models to the same covariates for these cumulative incidence data. RESULTS: The Kaplan-Meier estimates of OS and PFS at 4 years were 51% and 26%, respectively. There was no statistical difference in the OS in patients who had MF alone, SS, MF with LCT, or SS with LCT. PFS at 4 years was superior in patients who had SS versus those who did not (52.4% versus 9.9%; P = 0.02). The cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 40% and 28%, respectively. The cumulative nonrelapse mortality rate was 16.7% at 2 years. CONCLUSION: Allogeneic SCT may result in long-term remissions in a subset of patients with advanced CTCL. Although post-SCT relapse rates are high, many patients respond to immunomodulation and achieve durable remissions. CLINICALTRIALSGOV: NCT00506129.

Are changes in HLA Ags responsible for leukemia relapse after HLA-matched allogeneic hematopoietic SCT?

Loss of heterozygosity (LOH) has been shown to be associated with leukemia relapse after haploidentical transplantation. Whether such changes are an important cause of relapse after HLA-matched transplantation remains unclear. We retrospectively HLA-typed leukemic blasts for 71 patients with AML/myelodysplastic syndrome obtained from stored samples, and the results were compared with those obtained at diagnosis and/or before the transplant. No LOH or any other changes in HLA Ag were found in any of the samples tested post transplant as compared with pretransplant specimens. One patient had LOH in HLA class I Ag (HLA-A,-B and -C); however, these changes were present in the pretransplant sample indicating that they occurred before the transplant. We concluded that, in contrast with haploidentical transplantation, HLA loss does not have a major role as a mechanism of relapse after allogeneic transplantation with a closely HLA-matched donor.

An update on allogeneic hematopoietic progenitor cell transplantation for myeloproliferative neoplasms in the era of tyrosine kinase inhibitors.

Myeloproliferative neoplasms are a category of diseases that have been traditionally amenable to allogeneic hematopoietic progenitor cell transplantation. Current developments in drug therapy have delayed transplantation for more advanced phases of the disease, especially for patients with CML, whereas transplantation remains a mainstream treatment modality for patients with advanced myelofibrosis and chronic myelomonocytic leukemia. Reduced-intensity conditioning has decreased the treatment-related mortality, and advances in the use of alternative donors for transplantation could extend the use of this procedure to an increasing number of patients with improved safety and efficacy. Here we review the current knowledge about allogeneic transplantation for myeloproliferative neoplasms and discuss the most important aspects to be considered when contemplating transplantation for patients with these diseases. Janus kinase 2 inhibitors offer the promise to improve spleen size and performance of patients with myelofibrosis and extend transplantation for patients with more advanced disease.

Clofarabine combined with busulfan provides excellent disease control in adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation.

We investigated the safety and early disease control data for i.v. busulfan (Bu) in combination with clofarabine (Clo) in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients (median age, 36 years; range, 20-64 years) received a matched sibling (n = 24), syngeneic (n = 2), or matched unrelated donor transplant (n = 25) for acute lymphoblastic leukemia in first complete remission (n = 30), second complete remission (n = 13), or active disease (n = 8). More than one-half of the patients had a high-risk cytogenetic profile, as defined by the presence of t(9;22) (n = 17), t(4;11) (n = 3), or complex cytogenetics (n = 7). Clo 40 mg/m(2) was given once daily, with each dose followed by pharmacokinetically dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic SCT 2 days later. The Bu dose was based on drug clearance, as determined by the patient's response to a 32-mg/m(2) Bu test dose given 48 hours before the high-dose regimen. The target daily area under the receiver-operating characteristic curve was 5500 µM/min for patients age <60 years and 4000 µM/min for those age ≥60 years. The regimen was well tolerated, with a 100-day nonrelapse mortality rate of 6%. With a median follow-up of 14 months among surviving patients (range, 6-28 months), the 1-year overall survival, disease-free survival, and nonrelapse mortality rates were 67% (95% confidence interval [CI], 55%-83%), 54% (95% CI, 41%-71%), and 32% (95% CI, 16%-45%), respectively. For patients undergoing SCT in first remission, these respective rates were 74%, 64%, and 25%. Our data indicate that the combination of Clo and Bu provides effective disease control while maintaining a favorable safety profile.

Reduced-intensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT.

Haploidentical SCT (HaploSCT) has been most commonly performed using a myeloablative, TBI-based preparative regimen; however, the toxicity with this approach remains very high. We studied the feasibility of a reduced-intensity conditioning regimen in a phase II clinical trial using fludarabine, melphalan and thiotepa and antithymocyte globulin (ATG) for patients with advanced hematological malignancies undergoing T-cell depleted HaploSCT. Twenty-eight patients were entered in the study. Engraftment with donor-derived hematopoiesis was achieved in 78% of patients after a median of 13 days. Six patients experienced primary graft failure, three out of four tested patients had donor-specific anti-HLA antibodies (DSA) (P=0.001). Toxicity included mostly infections. A total of 21 out of 22 patients with AML/myelodysplastic syndrome (MDS) achieved remission after transplant (16 with relapsed/refractory AML). Five out of the 12 patients (42%) with AML/MDS with <15% BM blasts survived long term as compared with none with more advanced disease (P=0.03). HaploSCT with this fludarabine, melphalan and thiotepa and ATG RIC is an effective, well-tolerated conditioning regimen for patients with AML/MDS with low disease burden at the time of transplant and allowed a high rate of engraftment in patients without DSA. Patients with overt relapse fared poorly and require novel treatment strategies.

Gallbladder adenoma with focal adenocarcinoma.

The majority of polypoid lesions of the gallbladder are cholesterolosis pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The case of a 52-year old male patient with an adenomatous polyp of the GB with focal adenocarcinoma is presented.

[Resection of the celiac axis increase resectability rate in locally advanced pancreatic body and gastric tumor]. / Rezectia de trunchi celiac--factor de crestere a rezecabilitatii in neoplasmele pancreatice si gastrice local avansate.

Celiac axis involvement in locally advanced neoplasia was considered in the past a criteria of non resectability. Carcinoma of the body and tail of the pancreas is often diagnosed at an advanced stage or metastatic stage. Gastric carcinoma (particularly antral localization) can also be locally invasive. Celiac axis can be invaded in both neoplasias. In order to increase resectability rate in those two types of neoplasia celiac trunk resection was proposed (en bloc with distal pancreatectomy, loco-regional lymph node excision with or without total gastrectomy). We report our experience on 3 patients and some considerations about this surgical technique from medical literature.

[Surgical treatment of liver metastases from colorectal cancer]. / Tratamentul chirurgical al metastazelor hepatice ale cancerului colo-rectal.

We analyze our experience over a 10-year period in the surgical treatment of liver metastases from colorectal cancer. Between 01.01.1995 and 08.31.2005 189 liver resections were performed in 171 patients with liver metastases from colorectal cancer (16 re-resections - 2 in the same patient and a "two-stage" liver resection in 2 patients). In our series there were 83 patients with synchronous liver metastases (69 simultaneous resections, 12 delayed resections and 2 "two-stage" liver resection were performed) and 88 metachronous liver metastases. Almost all types of liver resections have been performed. The morbidity and mortality rates were 17.4% and 4.7%, respectively. Median survival was 28.5 months and actuarial survival at 1-, 3- and 5-year was 78.7%, 40.4% and 32.7%, respectively. Between January 2002 and August 2005 hyperthermic ablation of colorectal cancer liver metastases has been performed in 6 patients; in other 5 patients with multiple bilobar liver metastases liver resection was associated with radiofrequency ablation and one patient underwent only radiofrequency ablation for recurrent liver metastasis. In conclusion, although the treatment of colorectal cancer liver metastases is multimodal (resection, ablation, chemotherapy and radiation therapy), liver resection is the only potential curative treatment. The quality and volume of remnant liver parenchyma is the only limitation of liver resection. The morbidity, mortality and survival rates after simultaneous liver and colorectal resection are similar with those achieved by delayed resection. Postoperative outcome of patients with major hepatic resection is correlated with the surgical team experience. The long-term survival was increased using the new multimodal treatment schemes.

Dural venous sinus thrombosis in a patient with sickle cell disease: case report and literature review.

We report a case of dural venous sinus thrombosis (DVST) in a patient who developed seizures following exchange transfusion for treatment of acute chest syndrome associated with sickle cell disease. Evaluation with magnetic resonance imaging and magnetic resonance venography of the brain indicated left sigmoid sinus thrombosis. The history and laboratory evaluation did not reveal any other inherited or acquired hypercoagulable states. This is the fourth case of dural venous sinus thrombosis associated with sickle cell disease reported in literature. The patient had a favorable outcome with early treatment of unfractionated heparin.