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.

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.

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.

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.

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.

[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.

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.

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.

[Therapy of malignant liver tumors using microwave and radiofrequency ablation]. / Terapia tumorilor hepatice maligne cu microunde si unde de radiofrecventa.

The aim of our study was to evaluate the efficiency for thermo-ablation with microwave and radiofrequency on patients with malignant liver tumors. From January 2002 to January 2005, in our Center of General Surgery and Liver Transplantation in 53 patients 70 sessions of thermoablation were carried out. The mean age was 58 years (25-79 years). Sex ratio men: women was 1.8 (34:19). The diagnosis was hepatocarcinoma in 38 patients (72%), liver metastases from colorectal cancer in 9 (17%) and from non-colorectal cancer (6-11%). The most tumors were single (36-68%). The mean diameter was 39.5 mm (9-94 mm). Percutaneous approach was used in 14 interventions (20%), laparoscopic in 2 (3%) and open approach in 54 cases (77%). We performed 54 sessions of microwave ablation in 42 patients and 8 sessions of radiofrequency ablation in 5 patients. Both methods were applied in 6 patients during 8 sessions. Tumor ablation was done together with liver resection in 10 patients (19%) and resections of other organs in other 8 patients (15%). Morbidity was 12%. The encountered complications were ascites, right pleural effusion and liver abscesses. There was no death. Total and partial necrosis was observed in 27, respectively 20 patients. Local recurrence occurred in one patient but distal liver recurrences were diagnosed in 13 patients. After thermoablation for partial necrosis, local or distal recurrences patients received arterial chemoembolization (5), systemic chemotherapy (23), liver resection (1) and transplantation (1). The mean survival at 1 year and 3 years was 77% and respectively 38%. Microwave or radiofrequency ablation is a simple treatment method, with proved efficiency and minimal risks whose main indication is unresectable tumor.

[Central pancreatectomy--indications, technique, outcomes]. / Pancreatectomia centrala--indicatii, tehnica, rezultate.

Central pancreatectomy is a conservative resectional procedure indicated for benign and low malignant tumors located in the neck and/or body of the pancreas. We report our experience on 5 patients and some considerations about this surgical technique from medical literature.

[Current treatment of hepatocellular carcinoma. Analysis of a series of 123 cases over a 5-year period]. / Tratamentul multimodal al carcinomului hepatocelular. Analiza unei experiente clinice de 123 de cazuri în 5 ani.

We analyze a 123-cases experience over a 5-year period in the treatment of hepatocellular carcinoma (HCC). Liver resection, transplantation and hyperthermic ablation of the tumor were used according to the indication and patient selection. Systemic chemotherapy followed resection in 18 cases and hyperthermic ablation in 5 cases. Chemo-embolisation was performed in patients to be transplanted and in other two patients with tumor destruction. A number of 86 liver resections were performed in 84 patients (2 re- resections in 1 patient, subsequently transplanted) - 43 on normal liver and 41 on cirrhotic liver. Postoperative mortality was 4.7% in non-cirrhotic and 4.9% in cirrhotic patients. Survival in non-cirrhotic patients was 77% at 1 year, 65% at 2 years, and constant - 45% at 3 and 4 years, whereas in cirrhotic patients it was 60%, 56%, 56% and 36% (Kaplan-Meyer actuarial survival rates). Nine patients underwent liver transplantation (4 OLTs, 3 living donor LT, 1 split LT and 1 "domino" LT); postoperative mortality was 11% (1 patient). At present five patients are alive and well. One patient died by peritoneal carcinomatosis at 10 months; another patient died at 6 months by severe cholestatic recurrent C virus hepatitis and one patient was discharged with permanent severe neurologic disturbances. In 31 patients hyperthermic ablation of the tumor was used with zero mortality. Actuarial survival rates were 75% at one year and 67% at 2 years. In conclusion, in non-cirrhotic patients with HCC resection is the treatment of choice. In cirrhotic patients limited resections should be preferred and liver transplantation is the best solution in selected cases; local ablative methods may be used for some unresectable tumors. The role of adjuvant chemotherapy has to be determined in future comparative studies.

[Orthotopic liver transplantation in adult patients with cadaveric grafts. Experience of the Fundeni Center of General Surgery and Liver Transplantation]. / Transplantul hepatic ortotopic de la donator cadavru la adult. Experienta Centrului de Chirurgie Generalai si Transplant Hepatic Fundeni.

We analyze the experience of the Center of General Surgery and Liver Transplantation from the Fundeni Clinical Institute (Bucharest, Romania) regarding orthotopic liver transplantation (OLT) in adult recipients, with whole liver grafts from cadaveric donors, between April 2000 (when the first successful LT was performed in Romania) and December 2004. This series includes 37 OLTs in adult recipients (16 women and 21 men, aged between 29-57 years--average 46 years). Other two LT with whole liver cadaveric grafts and two reduced-size LT were performed in children; also, in the same period, due to the acute organ shortage, other methods of LT were performed in 28 patients (21 living donor LT, 6 split LT and one "do mino" LT), that were not included in the present series. The indications for OLT were HBV cirrhosis--10, HBV+HDV cirrhosis--4, HCV cirrhosis--11, HBV+HCV cirrhosis--2, biliary cirrhosis--5, Wilson disease--2, alcoholic cirrhosis--1, non-alcoholic liver disease--1, autoimmune cirrhosis--1. With three exceptions, in which the classical transplantation technique was used, the liver was grafted following the technique described by Belghiti. Local postoperative complications occurred in 15 patients (41%) and general complications in 17 (46%); late complications were registered in 18 patients (49%) and recurrence of the initial disease in 6 patients (16%). Intrao- and postoperative mortality was 8% (3/37). There were two patients (5%) who died because of immunosuppressive drug neurotoxicity at more than 30 days following LT. Four patients (11%) died lately because of PTLD, liver venoocclusive disease, recurrent autoimmune hepatitis and liver venoocclusive disease, myocardial infarction, respectively. Thirty-four patients survived the postoperative period (92%); according to Kaplan-Meier analysis, actuarial patient-survival rate at month 31 was 75%.

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.

Liver hemangioma revisited: current surgical indications, technical aspects, results.

BACKGROUND/AIMS: New developments regarding the diagnosis of liver hemangiomas, surgical indication and therapeutic options emerged recently. We reviewed our experience from the point of view of these modern developments. METHODOLOGY: Fifty-seven patients with liver hemangiomas were retrospectively studied. The relationship between size, symptoms and treatment was assessed. RESULTS: Indication for surgery was the size of the lesion in 5 patients, symptomatology in 48 and uncertain diagnosis in 4. Increase in size was noted in four patients. Six patients had associated intraabdominal benign or malignant pathology. The treatment of choice was enucleation. Postoperative complications were noted in 6 patients and mortality was nil. In 3 patients the hemangiomas recurred and were reresected in 2. CONCLUSIONS: Hemangiomas should be resected when larger than 10 cm and when they become symptomatic. With the modern diagnostic work-up, uncertainty of diagnosis as an indication for surgery should be rare. Surgery remains the main treatment, with a low morbidity and mortality if performed in a specialized hepatobiliary unit. Enucleation is the surgical option of choice. In selected cases laparoscopic enucleation can be performed with good results.

[Laparoscopic splenectomy--lessons learned from a series of 40 cases. The advantages of the postero-lateral approach]. / Splenectomia laparoscopica--experienta primelor 40 de cazuri. O pledoarie pentru abordul postero-lateral.

Until October 2000 in our surgical department 40 patients underwent laparoscopic splenectomy. Seven patients were converted to laparotomy for completion of splenectomy. All of these occurred in the first 20 patients and were due to bleeding. There was no postoperative mortality. Postoperative complications occurred in two patients: one abdominal wall hematoma and a postoperative hernia. Indications were idiopathic thrombocytopenic purpura, hereditary spheocytosis, autoimmune hemolytic anemia and others. In the last 30 cases we used the postero-lateral approach, that results in reduced blood loss, fewer patients that needed to be converted to open surgery and shorter postoperative stay. Accessory spleens can be successfully localized and with a carefull technique the capsular fractures can be minimized reducing the risk of splenosis.

[Pancreaticoduodenectomy--the rutin surgery?]. / Duodenopancreatectomia cefalica--operatie de rutina?

Pancreaticoduodenectomy with or without pylorus preserving remains the only possibility for cure for the patients with malignant tumors of duodenum, periampullary and cefalopancreatic region, and distal biliary tumors; Pancreaticoduodenectomy is proceeded also for benign tumors of the head of the pancreas (chronic pancreatitis, cysts) but today the standard became preserving duodenum pancreatectomy with good functional results comparing with standard Whipple resection. The last decade had shown a dramatically decrease of the postoperative death for this kind of operations, centers with high volume have been reported a postoperative mortality rate between 1-3%. Our study is a retrospective analysis witch compare the postoperative mortality between 1 January 1990-1 October 2002. The results have shown a decrease of the postoperative mortality from 30.4% (1990-1995) to 9.8% (1995-1999) and 3.6% in the last three years (2000-2002). Also the surgeon volume of operation is closely linked with the postoperative mortality, at the first operations the postoperative mortality rate is 20-33% and after 20 pancreaticoduodenectomy the rate decrease dramatically to 2.6-5.5%. We conclude that pancreatodudenectomy today is routine operation which mortality have decreased at 5% and should be performed in high volume hospitals by surgeons with sufficient experience to minimize the postoperative death.

[Central hepatectomy]. / Hepatectomia centrala.

Central hepatectomy (CH) is a major liver resection that removes Couinaud's segments IV, V and VIII, indicated for centrally located lesions and designed to preserve functional parenchyma and prevent liver failure. During an 8-year period between January 1995-November 2002, 507 liver resections were performed in Fundeni Center of General Surgery and Liver Transplantation (Bucharest). There were three CH performed for colorectal metastases (1 case) and inflammatory pseudotumor (2 cases). The mean duration of the procedure and the mean blood loss were, respectively, 231 minutes and 915 ml. The patients had a good post-operative course, with only minor complications.

[Neoadjuvant radiochemotherapy in the treatment of esophageal squamous carcinoma:Preliminary results in a series of 15 patients]. / Radiochimioterapia neoadjuvanta în tratamentul carcinomului epidermoid esofagian. Rezultate preliminare pe un lot de 15 pacienti.

The purpose of this study is to analyze the experience of the Center of General Surgery and Liver Transplantation from Fundeni Clinical Institute (Bucharest) regarding the results of neoadjuvant radiochemotherapy in the squamous carcinoma of the esophagus. During 01.01.2001-09.07.2003, 15 patients with squamous carcinoma of the esophagus were treated using neoadjuvant radiochemotherapy (RCT); 13 patients (86%) underwent esophageal resection (in 2 patients resection was not possible due to the mediastinal invasion). Complete histological response (the lack of malignant tissue on the esophagectomy specimens) was noted in 5 cases. The morbidity and mortality rates were 48%, respectively 6%. RCT increases the resectability in esophageal cancer and decreases the postoperative morbidity and mortality.