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Deferasirox is an oral iron‐chelating agent having possible antileukemia and immune modulatory effects. Few reports have evaluated deferasirox in the setting of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We investigated the impact of deferasirox after allo‐HSCT in acute myeloid leukemia (AML). Of 326 consecutive patients undergoing allo‐HSCT in remission, analysis of 198 patients not receiving deferasirox revealed the negative prognostic effect of hyperferritinemia (≥1000 ng/mL) before and after allo‐HSCT on survival mainly due to increase in relapse. Of 276 patients with hyperferritinemia at 1 month after allo‐HSCT, 128 patients (46%) received deferasirox. Deferasirox induced a faster decline in serum ferritin level with a manageable safety profile, which significantly reduced relapse rather than nonrelapse mortality, resulting in better survival compared to patients not receiving deferasirox. Of note, the deferasirox group had a significantly higher incidence of chronic graft‐vs‐host disease, indicating improved graft‐vs‐leukemia (GVL) effects evidenced by the presence of suppressed regulatory T cells and sustained higher proportion of NK cells in peripheral blood. This study firstly demonstrates the improved survival and restoration of GVL effects of patients with AML by deferasirox, which also clarifies the detrimental effect of hyperferritinemia through after allo‐HSCT. Survival outcomes were improved according to iron chelation with deferasirox after allogeneic hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to evaluate the long-term outcomes of allogeneic stem cell transplantation ( SCT) in patients with paroxysmal nocturnal hemoglobinuria ( PNH) with or without aplastic anemia ( AA). Method A total of 33 patients with PNH clones who underwent allogeneic SCT were analyzed. Results After a median follow-up of 57 months (range, 6.0-151.3), the 5-year estimated overall survival rate was 87.9±5.7%. Four patients died of transplant-related mortality ( TRM). With the exception of one patient with early TRM, 32 patients were engrafted. Two patients who had developed delayed GF received a second transplant and recovered. The cumulative incidences of acute graft-vs-host disease ( GVHD) (≥grade II) and chronic GVHD (≥moderate) were 27.3±7.9% and 18.7±7.0%, respectively. Twenty-one patients receiving SCT with reduced-intensity conditioning ( RIC) had available follow-up data for PNH cell population for the first 6 months post-transplant. Analysis of these data revealed that the PNH clones disappeared within approximately 2 months. Conclusion RIC regimen was sufficient to eradicate PNH clones with sustained donor-type engraftment after allogeneic SCT. Therefore, application of allogeneic SCT with RIC should be considered in patients with PNH, in accordance with the severity of the underlying bone marrow failure. [ABSTRACT FROM AUTHOR]

In relapsed or refractory non-Hodgkin lymphoma (NHL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides graft-versus-lymphoma activity resulting in fewer incidences of relapse. However, therapy-related mortality (TRM) remains an important challenge. We attempted to introduce our reduced-intensity conditioning (RIC) regimen. From 2007 to 2013, we treated 28 relapsed or refractory NHLs with allo-HSCT. All were pre-conditioned with fludarabine [FLU, 180 mg/body surface area (BSA)/6 days] and melphalan (MEL, 70 mg/BSA/1 day); 25 (all but 3) were additionally treated with total body irradiation (TBI, 800 cGy/4Fx/2 days). Peripheral blood stem cells were collected from matched siblings (n = 10) or suitably matched unrelated (n = 18) donors. There were eight diffuse large B-cell lymphomas, seven peripheral T-cell lymphoma not otherwise specified, give lymphoblastic lymphomas, two mantle cell lymphomas, and six various other lymphomas. Of these patients, 10 relapsed after auto-HSCT, 5 relapsed after chemotherapy, and 13 were refractory lymphomas. After allo-HSCT, complete remission was achieved in 22 (78.5%) patients. After a median follow-up of 24.8 months, 3-year overall survival and disease-free survival were 62.4 and 59.2% and the 3-year TRM and relapse incidence were 14.9 and 28.6% respectively. Acute and chronic graft-versus-host diseases (GVHDs) were identified in 17 (≥Grade II in 12 patients) and 18 patients respectively, and the group with chronic GVHD showed favourable survival outcomes. In relapsed or refractory NHL, RIC-allo-HSCT using FLU + MEL + 800 cGy TBI showed favourable survival outcomes with acceptable TRM and relapse incidence. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Few studies have been performed to identify factors that are associated with an increased risk of infections during the neutropenic period in patients undergoing allogeneic stem cell transplantation (allo- SCT). The aim of this study was to identify the host immune cells responsible for infections before engraftment. Methods A total of 282 patients who underwent allo- SCT were enrolled. Peripheral blood samples were collected before conditioning therapy. Expression of CD161-expressing T cells, natural killer cells, and immature myeloid cells was analyzed by flow cytometry. Microbially and clinically defined infections and fevers of unknown origin as proposed by the Immunocompromised Host Society were included in this study. Results The median age was 45 years (range, 16-68 years). Patients had various hematologic disorders and were transplanted from human leukocyte antigen ( HLA)-matched siblings, unrelated donors, and familial HLA-mismatched donors. In univariate analysis, younger age and a familial HLA-mismatched donor were risk factors for the occurrence of infections. After adjusting for potential variables in univariate analysis, multivariate analyses revealed that a lower frequency of CD3+ CD4+ CD161+ cells was significantly associated with the occurrence of neutropenic infections. An age of 35 years or younger and allografting from familial HLA-mismatched donors showed a trend toward higher infection rates. Conclusion Our data indicated that a lower frequency of CD3+ CD4+ CD161+ T cells in peripheral blood before conditioning therapy was associated with a higher incidence of infection during the neutropenic period. These results suggest that recipient innate T cells with expression of C-type lectin CD161 can guard against infections before engraftment. [ABSTRACT FROM AUTHOR]

Posaconazole was introduced as the primary antifungal prophylaxis ( PAP) in acute myeloid leukaemia ( AML) or myelodysplastic syndrome ( MDS) patients during remission induction chemotherapy. Data on breakthrough invasive fungal infections ( IFIs) from various centres are essential, as there are several considerations in treating IFIs in the posaconazole era. The aim of this study was to evaluate the effectiveness of posaconazole PAP and identify characteristics of IFIs at a single centre in Korea. We retrospectively reviewed consecutive patients with AML/ MDS undergoing remission induction chemotherapy between December 2010 and November 2013. Of the 424 patients, 140 received posaconazole and 284 received fluconazole prophylaxis. The incidence of breakthrough proven/probable IFIs (15.5% vs. 2.9%, P < 0.001) and empirical antifungal treatment ( EAFT) (45.8% vs. 12.9%, P < 0.001) decreased in the posaconazole group compared to the fluconazole group. In the posaconazole PAP group, two cases of breakthrough mucormycosis were noted among 13 proven/probable/possible IFI cases (15.4%). Overall and IFI-related mortality was 12.1% and 1.9% respectively. Fungus-free survival was significantly higher in the posaconazole group (74.7% vs. 87.1%, P = 0.028). Breakthrough IFIs and EAFT decreased significantly after posaconazole PAP. The benefit in fungus-free survival was noted with posaconazole PAP. Clinicians should be vigilant to identify non- Aspergillus IFIs with active diagnostic effort. [ABSTRACT FROM AUTHOR]

In Asia, the incidence of chronic lymphocytic leukaemia (CLL) is lower than in Western countries. Only a few studies of CLL have been conducted in Korea, and no long-term clinical outcome data are available. We assessed the frequency of common chromosomal aberrations in Korean CLL patients using interphase fluorescence in situ hybridization (FISH) and investigated their relationship to clinical outcomes. Between 2000 and 2011, conventional cytogenetic studies were performed in 58 patients, and FISH results were available in 48 patients. We used six DNA probes for the detection of del(13q14), trisomy 12, del(11q22), del(17p13), IGH rearrangement and del(6q23). Chromosomal aberrations were identified in 15 of 58 patients (26%) with conventional cytogenetic studies and in 25 of 48 patients (52%) with interphase FISH, including six patients with complex karyotypes. In contrast with the results of Western studies, trisomy 12 was the most common aberration, followed by IGH rearrangement, del(13q14), del(11q22) and del(17p13). Deletion of 6q23 was not observed, and isolated del(13q14) was less frequent than in Western studies. Compared with the other types of chromosomal aberrations, patients with del(11q22) and del(17p13) were more likely to be Rai stage 3-4 and Binet stage C, resulting in poor responses to chemotherapy and worse outcomes. In contrast, patient with trisomy 12 and isolated del(13q14) showed better responses and superior survival outcomes. The incidence of CLL is lower in Korea than in Western countries, and the frequency of chromosomal aberrations differs, perhaps reflecting differences in the pathogenic mechanism between ethnicities. Large prospective studies are needed to further assess the prognostic value of these results in Korean CLL patients. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background In unrelated donor allogeneic stem cell transplantation ( URD- SCT), most studies reported that peripheral blood stem cells ( PBSC) resulted in higher incidence of acute and/or chronic graft-versus-host disease ( GVHD) without survival benefits compared with bone marrow (BM). To overcome these shortcomings of PBSC, we have used a risk-adapted GVHD prophylaxis for patients that received HLA-matched URD- SCT, which was adding low-dose rabbit antithymocyte globulin (Thymoglobulin®, 1.25 mg/kg for 2 d) to conditioning in the transplants with PBSC and not BM. Methods To determine whether this strategy is effective, we analyzed 115 adult patients with acute myeloid leukemia who received HLA-matched URD- SCT with PBSC ( n = 70) or BM ( n = 45) using our risk-adapted GVHD prophylaxis strategy. Results The PBSC group showed faster neutrophil (11 d vs. 13 d; P < 0.01) and platelet (12 d vs. 18 d; P < 0.01) engraftment compared with the BM group. No difference was observed in the incidence of acute GVHD grade II-IV at 100 d (54.3% vs. 64.4%; P = 0.38) and chronic GVHD at 4 yr (65.1% vs. 60.0%; P = 0.83). Other outcomes including the incidence of relapse (30.8% vs. 31.2%; P = 0.53), non-relapse mortality (13.5% vs. 6.9%; P = 0.24), disease-free survival (55.7% vs. 61.9%; P = 0.68), and overall survival (62.2% vs. 63.2%; P = 0.96) at 4 yr were not significantly different. Conclusion Our risk-adapted GVHD prophylaxis strategy resulted in similar transplant outcomes including comparable incidence of GVHD between the PBSC and BM groups in HLA-matched URD- SCT. [ABSTRACT FROM AUTHOR]

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]

High levels of expression of Wilms' tumor gene 1 ( WT1), survivin, or telomerase reverse transcriptase ( TERT) genes are introduced as leukemia-associated targets predicting clinical outcome. We prospectively investigated the leukemia-associated gene transcripts by real-time quantitative polymerase chain reaction from 151 adult patients with AML associated with the patients' clinical characteristics. The maximum levels of each gene in bone marrow were 64.4-, 8.1-, and 3.9-fold higher than those in the normal control, respectively. In contrast to the WT1 and TERT levels, survivin showed comparatively higher expression in the unfavorable cytogenetic group of patients. We found a significant difference in s urvivin levels between the CR and non- CR groups ( P = 0.0237). TERT expression levels were higher in patients who had a greater number of peripheral blood leukemic blasts at diagnosis ( P = 0.0191). Non- MRC subtypes and patients without specific mutations were the most powerful predictive factors for a better CR rate, by multivariate analyses. The lower levels of both WT1 and survivin co-expression ( P = 0.0129) and both survivin + TERT co-expression ( P = 0.0115) were significant factors for better OS. Besides lower initial levels of serum ferritin ( P = 0.0401), lower levels of WT1 ( P = 0.0438) and survivin ( P = 0.0401), lower levels of both WT1 and survivin co-expression ( P = 0.0031), and the three-gene combination of lower WT1 + survivin + TERT ( P = 0.0454) were powerful predictive factors for better EFS. As our findings were based on a single disease entity, that is, adult AML, they suggest that the expression of these genes may be critical for the immunobiology of AML to influence the clinical outcome in various ways. [ABSTRACT FROM AUTHOR]

No consecutive analysis of BAALC and WT1 expressions associated with core-binding factor AML ( CBF- AML) from diagnosis to hematopoietic stem cell transplantation ( HSCT) has yet been reported. We investigated BAALC and WT1 expressions using a method of real-time quantitative polymerase chain reaction ( RQ- PCR) at diagnosis, after induction chemotherapy, at pre- HSCT, and at post- HSCT period in 45 consecutive patients [t(8,21) ( n = 28), inv(16) (n = 17)], who received HSCT as a post-remission treatment. BAALC and WT1 RQ- PCR decrement ratio ( DR) was also calculated at post-induction chemotherapy, at pre- HSCT, and at post- HSCT compared with the diagnostic level. Higher BAALC expression at diagnosis showed significantly inferior OS ( P = 0.031), EFS ( P = 0.011), and higher CIR ( P = 0.002) rates. At post- HSCT, both higher BAALC and WT1 expressions showed significantly inferior OS ( P = 0.005, 0.016), EFS ( P = 0.002, 0.006), and higher CIR ( P = 0.001, 0.003) rates. A subgroup of t(8;21) showing higher BAALC and WT1 expressions at post- HSCT were also associated with inferior OS ( P = 0.018, 0.015) and higher CIR rates ( P = 0.019, 0.011). While BAALC DR showed no significant results on outcomes, WT1 DR more than 2-log at post- HSCT showed significantly lower CIR rate ( P = 0.028). This study showed that higher post- HSCT BAALC and WT1 expressions in patients with CBF- AML may be good markers of minimal residual disease for the prediction of survival and relapse after HSCT. [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]

This study describes a retrospective analysis on the transplant outcome of 56 consecutive patients with myelodysplastic syndrome ( MDS) according to their response to hypomethylating agents ( HMA). While 2-yr disease-free survival ( DFS) of patients who transformed to acute myeloid leukemia ( n = 12) was 25%, that of the remaining patients with MDS according to response to HMA was 73.1%, 68.1%, 50.0%, and 20.8% in G- COR (group of continuous response, n = 19), G- No C (group of no change, n = 15), G- LOR (group of loss of response, n = 6), and G- DP (group of disease progression, n = 4), respectively. When dichotomized as G- COR/ G- No C versus G- LOR/ G- DP, significantly different 2-yr DFS (71.0% vs. 33.3%; P = 0.004) and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate analysis, G- LOR/ G- DP [hazard ratio ( HR), 3.91; P = 0.008] and poor karyotype at transplantation ( HR, 2.69; P = 0.017) were the significant predictors for poor DFS, as G- LOR/ G- DP was for relapse ( HR, 6.28; P = 0.011). DFS was significantly poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P = 0.001) or higher-risk MDS ( Hr MDS) at the time of HMA (80.7% vs. 29.2%; P = 0.005). G- COR showed a trend of better DFS compared with G- No C among Hr MDS (74.6% vs. 36.5%; P = 0.090). These results implicate the significance of response to HMA on hematopoietic stem cell transplantation ( HSCT) outcomes and support the need for future study to verify the suggested strategy of proceeding to transplantation before LOR or DP, especially for Hr MDS. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the optimum conditioning intensity for allogeneic stem cell transplantation (SCT) in young (age ≤50), lower-risk (INT-1 by IPSS) Myelodysplastic syndrome (MDS) patients without significant comorbidities (hematopoietic cell transplantation-comorbidity index score ≤3). Methods: Transplant outcomes from 46 consecutive patients were retrospectively analyzed according to the conditioning intensity: reduced-intensity conditioning (RIC; n = 14), intensified RIC by adding low-dose total body irradiation (iRIC; n = 15), and myeloablative conditioning (MAC; n = 17). Results: After a median follow-up of 73.7 months, RIC had a better 4-yr overall survival (OS) (92.9%) compared with the iRIC (64.2%) or MAC (70.6%). Multivariate analysis showed that RIC was associated with improved OS compared with the MAC [relative risk (RR) of 0.08, P = 0.022] because of a lower transplant-related mortality (TRM) (RR, 0.08, P = 0.035). iRIC failed to show survival benefits over the MAC (RR of 0.77, P = 0.689) because of similarly high TRM (RR of 0.41, P = 0.480). Cumulative incidence of acute and chronic graft-versus-host disease (GVHD) after RIC was higher, but GVHD-specific survival was significantly better (RIC 100% vs. iRIC 45.7% vs. MAC, P = 0.018). Relapse rate was not different among the three groups, but in the RIC group, azacitidine was available and useful for inducing remission in two patients. Conclusion: This study shows that RIC improved OS by directly lowering TRM and indirectly giving an additional chance for relapsed MDS in the era of hypomethylating treatment. RIC-SCT should be considered for relative healthy lower-risk MDS patients. [ABSTRACT FROM AUTHOR]

Summary Invasive aspergillosis (IA) remains an important cause of mortality in acute leukaemia patients. Previous studies reported that serum galactomannan (GM) levels correlate strongly with IA outcomes in patients with haematological cancers. This study aimed to clarify the usefulness of serial GM testing for outcome evaluation of IA in acute leukaemia patients. We retrospectively analysed 58 acute leukaemia patients who had IA during neutropenic period after chemotherapy and whose serum GM was serially monitored until discharge or death. The kappa correlation coefficient was used to determine the strength of correlation between GM and clinical outcome (survival or death) of IA. The correlation between clinical outcome and GM kinetics was good at week 6 [κ = 0.663, 95% confidence interval (CI): 0.465-0.861] and excellent at week 12 (κ = 0.819, 95% CI: 0.667-0.91). Survival was significantly better in patients whose GM values normalised than in patients with persistently positive GM ( P < 0.0001) regardless of whether neutropenia resolved or acute leukaemia responded to chemotherapy. In neutropenic patients with acute leukaemia, serum GM correlated strongly with survival outcome of IA. This finding further supports the usefulness of the GM index as a surrogate marker for assessing IA outcome and the need for serial GM testing in therapeutic monitoring. [ABSTRACT FROM AUTHOR]

To correlate clinical outcomes with the expression of interleukin-2 receptor alpha (CD25) positive cells during induction chemotherapy (IC) in adult patients with acute myeloid leukaemia (AML), we investigated the prognostic importance of subsets of peripheral blood (PB) CD45+CD25+ cells. Seventy-five patients with newly diagnosed AML received the same initial IC; and serial PB samples were taken. The gated CD45/CD25 cell populations were used to compare the intensity of immunophenotypic signals based on the treatment timeline. Patients who responded poorly to IC demonstrated exceptionally higher levels of PB CD45+CD25+ cells by percentage ( p = 0.003) or by absolute count ( p = 0.046) on the seventh day (D + 7) of initial IC. In addition, patients in complete remission (CR) ( n = 61) demonstrated relatively lower levels of steady PB CD45+CD25+ after standard IC. These results suggest that the expression of CD25 can be used to predict the response to IC during an early period of treatment. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Summary. The aim of this study was to evaluate the outcomes for Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) patients in remission treated with allogeneic bone marrow transplantation (BMT). Twenty-three adults were entered onto this study. The 2-year probabilities of relapse and disease-free survival (DFS) were 39·4 ± 11·6% and 43·5 ± 10·3% respectively. The presence of chronic graft-versus-host disease (GVHD) was found to be an independent predictive factor affecting lower relapse and DFS. To monitor the BCR-ABL transcript, we also analysed 48 bone marrow samples of eight patients using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR). The kinetics of the BCR-ABL transcript correlated well with the patients' clinical course. In six patients who were in continuous remission after BMT, a rapid decrease in BCR-ABL copy number to the PCR-negative status was observed after the development of chronic GVHD. Meanwhile, routine bone marrow examination of two patients showed PCR positivity with a 3 or 4-log increase of BCR-ABL copy number and subsequent haematological relapse, which occurred 2 and 4 months later respectively. Although our data should be interpreted cautiously, the presence of chronic GVHD may reduce the risk of relapse in Ph+ ALL. Real-time quantitative RT-PCR appears to be a useful test for BCR-ABL transcript monitoring. [ABSTRACT FROM AUTHOR]

Abstract: The reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with fluorescence in situ hybridization (FISH) and real-time quantitative RT-PCR (RQ-PCR) for minimal residual disease (MRD) monitoring in 266 post-transplant bone marrow samples from 78 patients with chronic myelogenous leukemia (CML). The sensitivities of FISH to BCR-ABL positive samples determined by first-round (1st) RT-PCR, second-round (2nd) RT-PCR, and RQ-PCR were 64.2%, 25.8%, and 20.7%, respectively. The BCR-ABL/ABL ratio by RQ-PCR had a mean of 0.000 13 in the 1st RT-PCR-negative samples and 1.42 in the 1st RT-PCR-positive samples ( P <0.001), and means of 0.000 39 and 0.51 in the 2nd RT-PCR-negative and -positive samples ( P< 0.001). The mean ratios of BCR-ABL/ABL by RQ-PCR were significantly different in N/N (1st/2nd RT-PCR) or N/P and P/P ( P <0.001), but not in N/N and N/P, which showed that the discriminative power of RQ-PCR is confined to the 1st RT-PCR level. In this respect, monitoring of the 1st RT-PCR might be useful for estimating normalized BCR-ABL levels after transplantation. Nested RT-PCR was of limited use, as RQ-PCR quantified the BCR-ABL transcripts in 60 (91%) of 66 samples determined to be negative by 2nd RT-PCR. FISH was significantly correlated with RQ-PCR in FISH-positive samples ( n =24, r =0.79, P =0.001). An increase of FISH preceded that of RQ-PCR in a few cases with molecular relapse. By analyzing a large number of samples post-transplant, we found that RQ-PCR might be the most useful assay for MRD monitoring; however, FISH and RT-PCR were found to be useful complementary tools. [ABSTRACT FROM AUTHOR]

Summary. The prognostic relevance of karyotype has been established in adult acute lymphoblastic leukaemia (ALL) patients treated with chemotherapy but not definitively evaluated in an allogeneic bone marrow transplantation (BMT) setting. To determine the factors affecting the outcome of allogeneic BMT for adults with precursor B-lineage ALL in first or second complete remission (CR), a total of 41 consecutive patients with a successful karyotype were enrolled in this study. There were 21 men and 20 women with a median age of 27 (15–43) years. The distribution of French–American–British (FAB) subtypes was as follows: L1 (n = 26), L2 (n = 15). Unfavourable karyotypes (n = 12) were defined as Ph+ or t(4;11). Disease status at the time of transplant was first CR (n = 35) or second CR (n = 6). With a median follow-up of 36 months, the 3-year probabilities of relapse and disease-free survival (DFS) were 36·3 ± 8·4% and 57·3 ± 8·4% respectively. Potential variables predicting worse relapse and DFS were FAB subtype (L2), extramedullary involvement, pre-BMT status (second CR), unfavourable karyotype and type of graft-versus-host disease (GVHD). Further multivariate analysis showed that karyotype and pre-BMT status were independently associated with relapse and DFS. In addition, chronic GVHD was found to be significantly associated with a lower relapse rate. [ABSTRACT FROM AUTHOR]

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 CliniMACS 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., (© 2013 John Wiley & Sons Ltd.)

Objective: To investigate the immunoregulatory effects of allogeneic mixed chimerism induced by T cell-depleted, nonmyeloablative bone marrow transplantation (BMT) on chronic inflammatory arthritis and autoimmunity in mice deficient in interleukin-1 receptor antagonist (IL-1Ra)., Methods: IL-1Ra(-/-) mice (H-2K(d)) were treated with antibody to asialoganglioside G(M1) (anti-natural killer cell), total body irradiation (500 cGy), and T cell-depleted, nonmyeloablative BMT derived from C57BL/6 mice (H-2K(b)). Engraftment and chimerism were evaluated in peripheral blood, lymph nodes, and spleen by multicolor flow cytometry. The severity of arthritis was evaluated by clinical scoring and histopathologic assessment. Levels of IgG1 and IgG2a subtypes of anti-type II collagen (anti-CII) antibodies were measured in serum samples. After T cells were stimulated with CII, ovalbumin, and phytohemagglutinin, T cell proliferative responses and levels of cytokine production (interferon-gamma [IFNgamma], tumor necrosis factor alpha [TNFalpha], interleukin-10 [IL-10], and IL-17) were assayed in culture supernatants., Results: All IL-1Ra(-/-) mice receiving BMT showed marked improvement in arthritis within 3 weeks, as well as successful induction of mixed chimerism. These mice showed higher levels of IgG1, and lower levels of IgG2a anti-CII antibodies and weaker T cell proliferative responses than did mice in the control groups (either no treatment or conditioning alone without bone marrow rescue). In mixed chimeras, the levels of IFNgamma, TNFalpha, and IL-17 produced from CII-stimulated T cells were significantly suppressed and IL-10 production was significantly higher as compared with controls., Conclusion: The introduction of allogeneic mixed chimerism showed a strong immunoregulatory potential to correct established chronic inflammatory arthritis and autoimmunity originating from a dysregulated proinflammatory cytokine network.