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The major limitation of autologous stem cell transplantation (auto- SCT) in non- Hodgkin lymphoma ( NHL) is relapse. Although autologous graft contamination may be a potential cause, prior purging of the autograft remains controversial. Therefore, we retrospectively analysed 56 consecutive patients with NHL receiving auto- SCT at complete ( n = 41) or partial remission ( n = 15). Among them, 24 patients underwent autograft manipulation with positive selection of CD34+ cells using a Clini MACS device (purged group). Twenty-five patients had received ≥2 previous chemotherapy regimens before auto- SCT. After a median follow-up of 41·4 months, transplant-related mortality was observed only in unpurged group ( n = 2; 3·6%). The 3-year overall survival (91·7% vs. 56·1%, P = 0·009) and progression-free survival (78·7% vs. 53·1%, P = 0·034) favoured CD34+ purification. While neutrophil recovery was similar, platelet recovery was delayed in the purged group. Cytomegalovirus reactivation was predominantly observed in the purged group, although no other clinically unmanageable infectious complications occurred. Although this study has the inevitable limitations of heterogeneity in previous treatment and NHL subtypes, and a small number of patients analysed, the high survival rate in the purged group may suggest the need for prospective randomized trials to determine the role of CD34+ purification in auto- SCT for NHL. [ABSTRACT FROM AUTHOR]

Abstract: Using real-time quantitative PCR, we monitored Wilms tumor gene 1 (WT1) expression from diagnosis to hematopoietic stem cell transplantation (HSCT) in adult patients with cytogenetically normal acute myelogenous leukemia (CN-AML) and FLT3-ITD and NPM1 mutations. The values at diagnosis were evaluated in 104 patients. Data collected after induction chemotherapy were available for all patients, but only 68 patients were treated with HSCT. Significant WT1 expression cut-offs were determined by receiver operation characteristic curve analysis, and rates of overall survival (OS) and disease-free survival (DFS) were estimated. WT1 decrement ratios (DR) at postinduction chemotherapy and at pre- and post-HSCT compared with the diagnostic level were calculated. Higher WT1 expression at diagnosis, postinduction chemotherapy, and pre-HSCT showed inferior OS (P = .015, <.001, and .002) and DFS (P = .006, <.001, and .003). The cut-offs were determined at the median for diagnostic WT1 expression and at the 25% level from the top for other time points excluding post-HSCT. The WT1 DR ≥ 1-log after induction chemotherapy showed superior OS and DFS (P = .009 and .002) and WT1 DR ≥ 1-log preceding HSCT also showed superior OS and DFS (P = .009 and .003). Results of WT1 DR were consistently applicable in each subgroup with higher (≥1.0) and lower (<1.0) WT1 expression at diagnosis and also in NPM1-wild-type/FLT3-ITD–negative CN-AML. The WT1 DR therefore predicted survival outcomes after HSCT more accurately than did the diagnostic WT1 expression. WT1 expression may serve as a reliable marker for residual disease and WT1 DR as a prognostic indicator, particularly in NPM1-wild-type/FLT3-ITD–negative CN-AML. These measures may be applied throughout the course of treatment and even after HSCT. [Copyright &y& Elsevier]

Objective: As data on the effectiveness of tumor markers in detecting hepatocellular carcinoma (HCC) in cirrhotic patients are limited, we investigated the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), andLens culinarisagglutinin-reactive fraction of AFP (AFP-L3).Material and methods: This retrospective study enrolled 361 cirrhotic patients with HCC, and 276 cirrhotic patients without HCC occurrence.Results: Most patients were men (n = 431, 67.7%); the median age was 57.0 years. The main etiology of chronic liver disease was chronic hepatitis B (n = 467, 73.3%). The sensitivity and specificity of combined three biomarkers was 87.0 and 60.1% in overall HCC, and 75.7 and 60.1% in early HCC, respectively (cutoff: 20 ng/mL for AFP, 40 mAU/mL for PIVKA-II, and 5% for AFP-L3). The area under the receiver operating characteristic curve (AUROC) for HCC diagnosis was 0.765 (95% confidence interval [CI], 0.728–0.801) for AFP; 0.823 (95% CI, 0.791–0.854) for PIVKA-II; and 0.755 (95% CI, 0.718–0.792) for AFP-L3. The AUROC for early HCC diagnosis was 0.754 (95% CI, 0.691–0.816) for AFP, 0.701 (95% CI, 0.630–0.771) for PIVKA-II, and 0.670 (95% CI, 0.596–0.744) for AFP-L3. Combining the three tumor markers increased the AUROC to 0.877 (95% CI, 0.851–0.903) for HCC diagnosis, and 0.773 (95% CI, 0.704–0.841) for early HCC diagnosis.Conclusion: Diagnostic accuracy improved upon combining the AFP, PIVKA-II, and AFP-L3 tumor markers compared to each marker alone in detecting HCC and early HCC in cirrhotic patients. [ABSTRACT FROM PUBLISHER]

Eighty adult patients with acute myeloid leukemia (AML) received peripheral blood T cell–replete HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Disease status at transplantation was either first or second complete remission (CR, n = 69) or relapse/refractory (n = 11). Identical transplant-related procedures with conditioning regimen consisting of fractionated 800 cGy total body irradiation (TBI), fludarabine (30 mg/m 2 /day for 5 days), busulfan (3.2 mg/kg/day for 2 days), and antithymocyte globulin (1.25 mg/kg/day on days −4 to −1) and graft-versus-host disease (GVHD) prophylaxis with tacrolimus and methotrexate were used in all patients. Recovery of neutrophil (median, 11 days) and platelet (median, 10 days) counts was achieved in all patients with full donor chimerism (≥99%), and no delayed engraftment failure was observed. The cumulative incidence of grades III to IV acute GVHD and moderate to severe chronic GVHD was 11.2% and 26.3%, respectively. A donor CD8 + and CD4 + T cell dose above the median value was significantly associated with the incidences of grades II to IV acute GHVD and moderate to severe chronic GVHD, respectively. After a median follow-up of 28 months for survivors, the 2-year cumulative incidences of relapse (n = 20) and nonrelapse mortality (n = 10) were 26.6% and 12.2%, respectively. Although all but 1 patient in relapse/refractory status died, the 2-year overall and progression-free survival of patients in first CR was 82.5% and 75.1%, respectively. We suggest the strategy of fractionated 800 cGy TBI-based conditioning with unmanipulated peripheral blood stem cell grafts seems feasible with favorable outcomes for adult patients with AML undergoing haplo-HSCT in CR. [ABSTRACT FROM AUTHOR]

Objectives For patients with acute myeloid leukemia in first complete remission ( AML CR1) lacking HLA-matched sibling donors ( MSD), 8/8-matched unrelated donors ( URD) are mostly used in cases with poor-risk features. For AML CR1 with intermediate cytogenetics, however, the benefit of 8/8-matched URD should be compared with non-allogeneic therapies as well as MSD. Methods To address this issue, we assessed the transplantation outcomes of 8/8-matched URD ( n = 54) compared with MSD ( n = 145) or autologous transplantation ( n = 89) for AML CR1 with intermediate cytogenetics. Results In multivariate analyses, 8/8-matched URD had comparable 6-yr overall survival (OS, P = 0.997), disease-free survival ( DFS, P = 0.951), and relapse ( P = 0.672) to MSD, whereas 8/8-matched URD had a higher OS ( P = 0.070) and DFS ( P = 0.035) with lower relapse ( P = 0.009) than autologous transplantation. No difference in non-relapse mortality was observed according to donor type. Notably, these equivalent or superior outcomes of 8/8-matched URD compared with MSD or autologous transplantation, respectively, were particularly evident in patients without poor-risk features ( n = 200), such as older age, hyperleukocytosis at diagnosis, and myelodysplasia-related changes, who are not usual candidates for URD transplantation. Conclusions These results indicate that 8/8-matched URD are feasible next option in AML CR1 with intermediate cytogenetics, when lacking MSD, even in patients without poor-risk features. [ABSTRACT FROM AUTHOR]