Reduced-intensity conditioning by fludarabine/busulfan without additional irradiation or T-cell depletion leads to low non-relapse mortality in unrelated bone marrow transplantation

In reduced intensity, allogeneic stem cell transplantation from unrelated donors (u-RIST), graft-versus-host disease (GVHD), graft failure, and non-relapse mortality (NRM) are persistent problems. Although anti-thymocyte globulin, alemtuzumab, and total body irradiation (TBI) have been explored as conditioning modalities for u-RIST, the necessity for T-cell depletion or TBI to prevent GVHD or facilitate engraftment in u-RIST has not been determined. We here report the use of u-RIST with bone marrow grafting, following a simple conditioning regimen of 180?mg/m(2) fludarabine and 8?mg/kg of oral or intravenous busulfan without TBI or T-cell depletion. The study population was exclusively Japanese patients with a history of prior chemotherapy. We retrospectively analyzed 31 consecutive patients (median age 53?years). Twenty-five patients (81%) were transplanted from HLA-A, -B, and -DRB1 allele-matched donors. In all patients, neutrophil engraftment was achieved. The cumulative incidence of grade II-IV acute GVHD was 42%. However, 77% of patients with acute GVHD improved with, and could be managed by, initial, systemic, high-dose steroid treatment alone. Two-year overall and event-free survival was 62 and 53%, respectively. The NRM of 10% at 2?years was relatively low. Our results suggest that u-RIST without TBI or T-cell depletion may improve the prognosis after u-RIST in certain patient populations.     

Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning

Despite the widespread adoption of reduced-intensity conditioning (RIC) for myeloma, there are few data comparing outcomes with RIC with myeloablative conditioning (MAC). We report the outcomes of patients undergoing allogeneic transplantations for myeloma and reported to the EBMT. A minimum data set was available on 320 RIC and 196 MAC allografts performed between 1998 and 2002. The RIC patients were older (51 vs 45 years) with more progressive disease (28% vs 21%) and more had received a prior transplant (76% vs 11%). In addition, there was a longer time to transplantation and an increased use of peripheral blood and T-cell depletion. For RIC and MAC, respectively, the nonrelapse mortality (NRM) at 2 years was 24% and 37% (P = .002); overall survival, 38.1% and 50.8% (not significant [ns]); and progression-free survival (PFS), 18.9% and 34.5% (P = .001). On multivariate analysis, RIC was associated with a reduction in NRM (HR, 0.5), but this was offset by an increase in relapse risk (HR, 2.0), and the conditioning intensity did not impact on overall survival or retain significance for PFS. These data suggest that there is a continuing need to investigate dose intensity in the conditioning for myeloma allografts.     

Cyclophosphamide, cytosine arabinoside and TBI as a conditioning regimen for allogeneic bone marrow transplantation in patients with leukemia.

This is a prospective study designed to determine the toxicity, efficacy and antileukemic effect of high-dose cytosine arabinoside (ara-C), cyclophosphamide and total body irradiation (TBI) as a myeloablative regimen prior to allogeneic bone marrow transplantation for patients with hematologic malignancies. Fifty-eight patients with hematologic malignancies were treated with cyclophosphamide, high-dose ara-C and total body irradiation (TBI) followed by allogeneic bone marrow transplantation. Fifty patients had good prognosis disease and eight had poor prognosis disease. Cyclosporine and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. The conditioning regimen consisted of ara-C 3000 mg/m2 twice a day x six doses on days -7, -6, and -5; cyclophosphamide 1800 mg/m2 on days -4 and -3; and TBI 1400 cGy midline dose at 5 cGy/min in eight total fractions administered twice a day on days -4, -3, -2, and -1. The bone marrow was infused on day 0 (zero). Toxicity related to the conditioning regimen was comparable to that reported with other conditioning regimens, except for diarrhea which appears to be more frequent. The actuarial survival at 1 year was 69% (58-82) and at 5 years was 54% (42-69) with the numbers in parentheses representing the 95% confidence interval of the Kaplan-Meier estimate. After a median follow-up of 28 months, 31 of 58 (53%) patients are alive without evidence of disease. Only four of the 58 patients (7%) have relapsed. Cyclophosphamide, ara-C and TBI is a safe and effective myeloablative regimen for patients with leukemia. The overall relapse rate in our study was 7% with a median follow-up of 28 months and appears to be lower than relapse rates reported in other series. This is probably due to the added antileukemic effect of ara-C. This regimen should be compared with other myeloablative regimens in a controlled study.     

Allogeneic bone marrow transplantation for children with histiocytic disorders: use of TBI and omission of etoposide in the conditioning regimen

The histiocytoses are rare disorders of antigen-processing phagocytic or antigen-presenting cells. Allogeneic bone marrow transplantation (BMT) can be curative of these disorders. We report a series of five children with Langerhans cell histiocytosis (n=2) or hemophagocytic lymphohistiocytosis (n=3), who received allogeneic BMT with a total body irradiation (TBI)-containing regimen (TBI, cytarabine, and cyclophosphamide) at our institution between 1995 and 2000. One of these patients received busulfan, cyclophosphamide, and etoposide for the first of two BMTs. All grafts except one (a matched sibling-donor graft) were T-cell-depleted grafts from unrelated donors. All received cyclosporine graft-versus-host disease (GvHD) prophylaxis; the recipient of the matched sibling graft also received methotrexate. Three patients engrafted at a median of 24 days after transplantation. The patient who did not receive TBI experienced primary graft failure and recurrent disease. After the TBI-containing conditioning regimen was given, a second transplant engrafted on day +17. One patient with concurrent myelodysplastic syndrome died of toxicity on day +33 without evidence of engraftment. No acute or chronic GvHD was observed. Four patients survive disease-free, a median of 63 months after transplantation, all with Lansky performance scores of 100. We conclude that a conditioning regimen containing TBI but not etoposide is effective in allogeneic BMT for children with histiocytic diseases.     

Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen

The optimal approach to stem cell transplantation in children with immunodeficiency who lack a matched family donor is controversial. Unrelated donor stem cell transplantation gives equivalent outcome to mismatched family donor stem cell transplantation in severe combined immunodeficiency, whereas unrelated donors may be preferable in non-severe combined immunodeficiency children. However, unrelated donor stem cell transplantation with conventional conditioning regimens has been associated with significant treatment-related toxicity, particularly in non-severe combined immunodeficiency patients with preexisting organ dysfunction. We report the outcome of a series of 33 consecutive unrelated donor transplantations performed at our center in children with primary immunodeficiency using a reduced-intensity conditioning regimen between 1998 and 2001. We have compared these outcomes with a retrospective control cohort of 19 patients who underwent transplantation with myeloablative conditioning between 1994 and 1998. All children in both groups had primary engraftment. There was no statistical difference in the speed of immune reconstitution or incidence of graft-versus-host disease between the 2 groups. Overall survival was significantly better in the reduced-intensity conditioning group: 31 (94%) of 33 patients survived, compared with 10 (53%) of 19 in the myeloablative conditioning group (P = .014). We conclude that the reduced-intensity conditioning regimen results in improved survival and reduced transplantation-related mortality compared with myeloablative conditioning in high-risk patients undergoing unrelated donor transplantation.     

Anthracyclines added to the conditioning regimen for allogeneic bone marrow transplantation are associated with a slower haematopoietic recovery

Factors which may influence haematopoietic recovery after allogeneic bone marrow transplantation were analysed. Forty-six evaluable patients transplanted with lymphocyte-depleted marrow for acute lymphoblastic leukaemia, acute non-lymphoblastic leukaemia, chronic myeloid leukaemia, myelodysplastic syndrome and severe aplastic anaemia were studied. The median time for platelet recovery to greater than or equal to 20 and to greater than or equal to 50 x 10(9)/l was 21 (9-72) and 26 (11-86) days respectively. The neutrophil recovery to greater than or equal to 0.5 x 10(9)/l and the leucocyte recovery to greater than or equal to 1.0 x 10(9)/l was 19 (8-47) and 18 (6-47) days respectively. No relation was found between the number of infused granulocyte-macrophage colony-forming cells, erythroid burst-forming cells, diagnosis, graft-versus-host disease, antibiotic administration and recovery. Addition of a continuous 6-day infusion of anthracyclines to the conditioning regimen delayed the median recovery of platelets, neutrophils and leucocytes by 7-9 days. Fever during aplasia also inhibited haematopoietic recovery. It is speculated that leakage of intracellular anthracyclines after bone marrow infusion or fever secondary to anthracyclines-induced oromucositis is responsible for the delayed bone marrow recovery.     

Melphalan/TBI is not more carcinogeneic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a period of 26 years

As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2-17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P < 0.0001). The cumulative overall risk of developing a SMN at 2, 5, 10 and 15 years post transplant was 0.4% (95% CI 0.1-2.6%), 1.7% (95% CI 0.6-4.4%), 6.4% (95% CI 2.8-10.8%) and 6.6% (95% CI 3.4-12.4%), respectively. Even though age-adjusted rates were higher than the general population melphalan/TBI was not associated with higher age-adjusted risk than Cy/TBI (increased risk 7.9 vs 11.4; P = NS). The cumulative overall risk of SMNs was not different with CY/TBI or Mel/TBI (8/393 vs 4/363; 10 year risk 4.4%, 95% CI 1.8-10.6 vs 8.4%, 95% CI 2.9-22.9; P = NS). The risk was significantly higher with use of additional cranial or cranio-spinal irradiation (17.5% vs 2.7% at 10 years; P = 0.0241). Transplants for acute lymphatic leukaemia resulted in a higher incidence of SMNs than did transplants for other diseases (ALL: 17.4%, 95% CI 6.3-42.6%; other diseases: 3.4% (95% 1.3-8.5%, P = 0.0469). The risk of SMN for patients with chronic GVHD was 8.4% (95% CI 3.7-18.7%) as compared to 3.5% (95% CI 1-11.1%) for patients without chronic GVHD (P = NS). No factor was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI.     

High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths.

Interleukin 10 (IL-10) is a potent inhibitor of proliferative T cell responses toward alloantigens, and suppresses the production of pro-inflammatory cytokines which are important in cellular activation and recruitment to sites of inflammation. Because of these properties, we hypothesized that high IL-10 production in patients prior to BMT may predict a better outcome. To investigate this, peripheral blood mononuclear cells (PBMNC) were obtained from 58 recipients (11 autologous, 25 related donor (RD), and 22 unrelated donor (URD)), prior to conditioning therapy. PBMNC were cultured for 24 h in the presence and absence of lipopolysaccharide (LPS) and culture supernatants were assayed for IL-10 using an ELISA method. Spontaneously produced and LPS-stimulated IL-10 levels were correlated with the development of transplant-related complications (TRC) including grade II-IV acute GVHD, veno-occlusive disease, idiopathic pneumonia syndrome and multi-organ dysfunction syndrome, and with death before day 100. For the autologous group, there were no TRC and only one death prior to day 100; therefore, no statistical comparisons to IL-10 levels could be made. In the RD group, 36% developed one or more TRC and 24% died before day 100; however, there were no statistically significant associations between spontaneous or LPS-induced IL-10 levels. In URD patients 41% developed TRC and 55% died prior to day 100. In this group, higher levels of spontaneous IL-10 production were associated with a lower overall occurrence of TRC (P = 0.03) and early death (P = 0.04). Our data would indicate that higher levels of IL-10 production prior to URD BMT may predict fewer TRC, as well as early deaths. The hypothesis that high IL-10 production prior to BMT may decrease complications following URD BMT warrants further testing.     

Reduced incidence of GVHD without increase in relapse with low-dose rabbit ATG in the preparative regimen for unrelated bone marrow transplants in CML

Summary:Antithymocyte globulin (ATG) treatment prevents graft failure and results in a low incidence of GVHD, but an increased risk of relapse could be expected as a consequence of reduced GVHD. From September 1995 to June 2001, 28 consecutive chronic myeloid leukemia (CML) patients underwent unrelated bone marrow transplants: 21 were in chronic phase (CP) and seven in advanced phase (AP). Median age was 35.5 years (range 20-50). HLA typing was based on high-resolution molecular techniques; in eight cases there were one or more allele mismatches. The preparative regimen consisted of TBI, EDX 120 mg/kg and rabbit ATG 15 mg/kg. All patients engrafted and no rejection occurred. Acute GVHD grade III-IV occurred in six patients (21%). Chronic GVHD occurred in 10 (40%) and it was extensive in one. Four out of seven patients transplanted in AP had a hematological relapse. Of 21 in CP, there was one cytogenetic and one molecular relapse: these two patients are now in complete remission with imatinib mesylate. With a median follow-up of 45.7 months, the 5-year survival is 76.2% for those transplanted in CP. These data demonstrate that transplants performed in CP, with low-dose ATG, are associated with a good outcome, low incidence of GVHD and no increase of relapse.     

Morbidity and non-relapse mortality after allogeneic bone marrow transplantation in adult leukemia patients conditioned with busulfan plus cyclophosphamide: a retrospective comparison of oral versus intravenous busulfan

We retrospectively compared morbidity and non-relapse mortality (NRM) after allogeneic bone marrow transplantation (BMT) in 236 adults with leukemia and myelodysplastic syndrome conditioned with cyclophosphamide plus oral versus intravenous busulfan. Our findings demonstrate that conditioning therapy with intravenous busulfan resulted in lower morbidity and NRM than did oral busulfan.     

Dose-adjusted bendamustine as a replacement for carmustine in autologous stem cell transplant conditioning for patients with relapsed lymphoma: A retrospective single-center study

BEAM conditioning regimen (carmustine [BCNU], etoposide, cytarabine, and melphalan) has been widely used for autologous stem cell transplantation in patients with relapsed or refractory lymphoma. However, BCNU-associated toxicities have prompted research to explore other options. This study aimed to assess the feasibility of bendamustine as an alternative to BCNU. We compared 71 patients who received either bendamustine (Benda-EAM group) or BCNU (BEAM group) conditioning. Considering previous reports of increased cardiotoxicity, nephrotoxicity, and mucositis, we adopted a lower bendamustine dose of 160 mg/m²/day administered for 2 days. There was no increase in nephrotoxicity and cardiotoxicity. Further, positive results were also obtained for neutrophil and platelet engraftment, appearing earlier in patients treated with Benda-EAM (10 vs. 14 days and 16 vs. 27 days, respectively). However, caution is warranted because an increased frequency of Grade 3 mucositis was observed in the Benda-EAM group (82.4% vs. 48%). This was accompanied by an increased need for parenteral nutrition. Despite the lower dose of bendamustine, the overall and progression-free survival rates were comparable between the Benda-EAM and BEAM groups. In conclusion, a lower dose of bendamustine may be an attractive alternative to BCNU as a tolerable treatment modality for patients with relapsed/refractory lymphoma.     

Allogeneic bone marrow vs. peripheral blood stem cell transplantation: a long-term retrospective single-center analysis in 329 patients

Objectives: Granulocyte colony‐stimulating factor‐mobilized peripheral blood hematopoietic stem cell transplantation (HSCT) provides a valuable and increasingly used alternative to bone marrow transplantation (BMT). This retrospective study aimed at determining whether the stem cell source is predictive for outcome, relapse incidence, non‐relapse mortality, and severity and incidence of both, acute and chronic graft‐versus‐host disease (GVHD) in patients undergoing allogeneic HSCT. Patients and methods: Between 1983 and 2007, 329 adult patients (median age 40, range 18–76) received a first allogeneic HSCT from either sibling (n = 203) or volunteer unrelated donors (n = 126) at our institution. The source of stem cells was bone marrow in 177 (54%) and peripheral blood in the remaining 152 (46%) patients. Results: Overall survival was 37% (31–43%, 95% confidence interval, CI), the relapse incidence was 30% (25–36%, 95% CI), and the non‐relapse mortality was 43% (38–49%, 95% CI) for the entire cohort with no significant differences between peripheral blood stem cell or BMT. In patients receiving myeloablative conditioning, peripheral blood stem cell transplantation (PBSCT) was associated with a significantly lower non‐relapse mortality (32% vs. 46%, P = 0.05), which, however, was restricted to standard‐risk disease (23% vs. 42%, P = 0.02). The overall cumulative incidences of acute GVHD II–IV were 51% and 54% following bone marrow and PBSCT, respectively. Severe acute GVHD III–IV was significantly more frequent after BMT (24% vs. 14%, P = 0.04), whereas chronic GVHD was significantly more frequent following PBSCT (48% vs. 24%, P = 0.0001). By multivariate analysis, PBSCT was only predictive for chronic GVHD (RR 2.29, P = 0.02). Conclusion: Although we failed to demonstrate any advantage of PBSCT over conventional BMT with regard to overall survival, relapse incidence and non‐relapse mortality PBSCT were associated with a significantly higher incidence of chronic graft‐versus‐host disease. Therefore, and by virtue of observations, that some patient groups might benefit from either stem cell source, there is still need for prospective randomized trials with special emphasize on quality of life in long‐term survivors.     

Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases

From April, 1985, to February, 1989, 102 consecutive patients received unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia (CML) at four centers. Median age of the group was 31 years (range, 4.5 to 51 years). Fifty-four patients were in first chronic phase (CP) at time of transplantation, and 48 had evidence of more advanced disease (AD) (accelerated phase, 32; blast crisis, 9; second CP, 7). In 44 cases, the donor and recipient were identical at the HLA A, B, and DR loci and were nonreactive in bidirectional mixed leukocyte culture (MLC) ("matched"). In 58 cases, nonidentity between donor and recipient could be determined at at least one HLA locus or in bidirectional MLC ("mismatched"). Fifty-eight patients were prepared for transplantation with a combination of cyclophosphamide and fractionated total body irradiation (FTBI) and received acute graft-versus-host disease (GVHD) prophylaxis consisting of methotrexate alone or in combination with cyclosporine, prednisone, or antithymocyte globulin (ATG). In 44 cases, patients received preparative agents in addition to cyclophosphamide and FTBI, and marrow depleted of mature T lymphocytes by ex vivo incubation with either anti-CD3 antibody plus complement (n = 24) or Campath-1 (n = 20). Engraftment defined by a peripheral blood neutrophil count greater than 0.5 X 10(9)/L was demonstrated in 92 cases and occurred at a median of 22 days (range, 11 to 46 days). In 10 cases, peripheral blood evidence of engraftment did not occur, and in one case, engraftment was followed by aplasia. Hematologic relapse was seen in four cases. Recurrence or persistence of the Ph1 chromosome without evidence of hematologic relapse occurred in four additional cases. The incidence of grade II to IV acute GVHD is 65% (95% confidence interval [CI], +/- 10%). After adjustment for recipient age and donor matching status, recipients of T lymphocyte-depleted donor marrow had a significantly lower incidence of grade II to IV acute GVHD (P less than .01); however, T depletion was not significantly associated with improved survival (P = .34), disease-free survival (P = .51), or increased incidence of relapse (P = .39). Of 102 patients, 46 are alive, with a median survival of 12 months (range, 3 to 46 months), and the Kaplan-Meier estimate of disease-free survival is 29% (95% CI, +/- 9%) for the entire group at 2 1/2 years.(ABSTRACT TRUNCATED AT 400 WORDS)     

Intensification of GVHD prophylaxis with low-dose ATG-F before allogeneic PBSC transplantation from HLA-identical siblings in adult patients with hematological malignancies: results from a retrospective analysis

Several studies have shown that chronic GVHD (cGVHD) is more frequent in patients receiving transplants from PBSC than in those receiving BM. In the setting of PBSC-unrelated transplants, the addition of anti-T-cell globulin (ATG) has shown a significant decrease in incidence/severity of cGVHD, without an increase in relapses or infections. However, no prospective data are yet available in the sibling setting. We retrospectively analyzed the effects of intensification of standard GVHD prophylaxis (CsA+MTX) by the addition of low-dose ATG in 245 patients receiving a transplant from HLA-identical sibling. From 1996 to 2001, patients received PBSC as the preferred source (group 2), and then ATG was added before transplant (group 3) because of a high cGVHD rate. Patients receiving BM in the same time period were analyzed as a control group (group 1). The incidence of grade III-IV acute GVHD and cGVHD was not significantly different in the three groups, but extensive cGVHD was highest in group 2 (38%) compared with group 3 (21%) or group 1 (28%; P=0.03). OS, TRM and time to relapse/progression were similar in the three groups. Our analysis shows that adding ATG to PBSC sibling allogeneic transplants can lower cGVHD, without an increase of relapse. Further prospective studies are needed to confirm these findings.     

Treatment of hemophagocytic lymphohistiocytosis with chemotherapy and bone marrow transplantation: a single-center study of 22 cases

Twenty-two children with hemophagocytic lymphohistiocytosis were treated with a chemotherapy regimen consisting of VP16-213, corticosteroids, and intrathecal methotrexate. A sustained clinical and biologic complete remission was obtained in 15 children and a partial remission in one child; six children died early of opportunistic infection (n = 4) or of disease progression (n = 2). Of the 16 children who were placed in first remission, 10 received maintenance chemotherapy alone, while six underwent bone marrow transplantation (HLA matched in five, HLA mismatched in one). Of the children who received chemotherapy alone, only two are in long-term remission after cessation of treatment. The remaining eight patients relapsed after a mean period of 5.4 months (range 2 to 8 months). Further treatment using the same regimen induced second remissions of short duration; death occurred after a median period of 2.3 months (range 0.5 to 6 months). A total of nine patients received allogeneic bone marrow transplantation (BMT). Among the six children transplanted in remission, four are in long-term unmaintained remission, 1 to 6 years after HLA-matched BMT. However, the relapse that occurred in one patient 1 year post BMT is difficult to interpret because the donor, the patient's 5-year-old sister, also developed the disease 1 year later. An HLA-nonidentical BMT resulted in unmaintained remission for 1 year, with autologous hematologic reconstitution followed by disease relapse. HLA-nonidentical BMT failed in three other patients with active disease at time of transplant. The poor long-term results of chemotherapy alone justify the use of related HLA-matched BMT in complete remission.     

Successful allogeneic bone marrow retransplantation with the same donor after graft rejection: Application of a modified conditioning regimen

Summary A 26-year-old man with severe aplastic anemia was treated with high-dose Cyclophosphamide followed by the infusion of bone marrow cells from his HLA-identical sister. After initial take of the graft, rejection ensued by day 46 which was followed by a permanent complete aplasia. After 4 months, bone marrow retransplantation with the same donor was attempted after a more intensive conditioning regimen. This led to permanent engraftment with rapid normalization of the blood counts lasting now for over 12 months. The patient has since remained in excellent clinical condition without signs of graft-versus-host disease.     

Clinical importance of bone marrow monocytic nodules in patients with myelodysplasia: retrospective analysis of 21 cases

Bone marrow monocytic nodules (MNs) can occur in various myeloid disorders. This retrospective review identified 21 patients with myelodysplasia who had unusual and distinct MNs. Eight patients had chronic myelomonocytic leukemia (CMML); 4 had acute myeloid leukemia (AML); and 9 had myelodysplastic/myeloproliferative diseases. In each case, the cells forming MNs expressed strong CD68. MNs appeared to persist even after aggressive chemotherapy, including conventional chemotherapy for 2 AML patients and high-dose chemotherapy preceding allogeneic bone marrow transplantation for 1 CMML patient. Thirteen of 21 patients (62%) died, and acute leukemic transformation was the main cause of death in 3 of 8 patients with CMML. The median survival of the 20 patients with appropriate follow-up was 9.8 months. Our findings demonstrate that MNs are associated with CMML, AML, myelodysplastic syndromes, and myeloproliferative diseases and suggest that MNs are resistant to intensive chemotherapy and patients with bone marrow MNs have a poor prognosis.     

Liver transplantation in nonalcoholic steatohepatitis is associated with high mortality and post-transplant complications: a single-center experience

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) with its progressive form nonalcoholic steatohepatitis (NASH) is the most common chronic liver disease in western countries which is associated with end-stage liver disease and hepatocellular carcinoma (HCC). This entity is a consistently increasing indication for transplantation. However, data about postsurgery outcome and complications are still limited. Patients and Methods: Records of 432 consecutive transplanted patients between October 2007 and January 2011 were investigated retrospectively. Forty transplants were performed due to NASH-induced cirrhosis. Perioperative courses and short- and long-term outcomes were analyzed. Results: The NAFLD population consisted of 16 women and 24 men with a mean age of 55 years. The median MELD score was 27 at the time of liver transplantion. BMI before surgery ranged from 21 to 45 (mean 31). Sixteen of the initial 40 patients are still alive. Patients with sustained obesity and features of the metabolic syndrome had a worse 1-year mortality rate of 42%. Conclusions: A significant number of liver transplantations in our center was performed due to NASH; transplantation in this cohort was associated with high mortality and postoperative complications, most likely due to associated obesity and diabetes. Weight reduction prior to surgery may lead to a better outcome.