ALBERT

Description: B cell non-Hodgkin’s lymphoma (B-NHL) consists of different pathological entities that are frequently characterized by distinct genetic alterations. However, the knowledge on these genetic lesions in B-NHL is still limited. In order to obtain a more comprehensive view of genetic lesions in B-NHL, we performed genome-wide analysis of copy number (CN) alterations as well as allelic imbalances using Affymetrix SNP arrays in 190 B-NHL cases, including 64 samples of diffuse large B-cell lymphoma (DLBCL), 62 of follicular lymphoma (FL), 64 of mucosa-associated lymphoid tissue lymphoma (MALT-L). SNP array data were analyzed with CNAG/AsCNAR software, which enabled sensitive detection of CN alterations in allele-specific manner, and thus allelic imbalances, without depending on availability of paired normal controls. Most frequent numerical abnormalities in B-NHL were gains of chromosomes 3 and 18, although gains of chromosome 3 were less prominent in FL. Chromosomal deletions that lead to loss of heterozygosity (LOH) were commonly found in 1p, 6q and 10q. However, the more chracteristic feature of B-NHL genomes was high frequency of CN netural LOH or uniparental disomy (UPD), which was found in 35 cases of DLBCL (55%), 32 cases of FL (52%) and 18 cases of MALT-L (28%). It is widely distributed in the genome, but more frequently found in 1p, 1q, 6p, 6q and 12q. High-grade amplifications and homozygous deletions frequently provide a clue to identify relevant gene targets. In our series, 12 loci of high-grade amplifications and 14 loci of homozygous deletions were identified, and helped to specify the candidate genes. These regions included, FCGR2B amplified in 5 cases of DLBCL, RERE amplified in 2 cases of FL and CDKN2A/CDKN2B deleted in 9 cases of DLBCL. The most notable finding in the current study was, however, the identification of common genomic alterations in genes that regulate activation of NFkB pathway in more than 50% of B-NHL cases. Eight lymphoma cases harbored high-grade amplification of cREL gene, and gain including cREL was detected in 28 samples (14.7%). Fourteen cases had gains or amplification of TRAF6, and another 16 cases had deletion at 10q including PTEN. These abnormalities were supposed to cause dysregulation of NFkB. Aberrant NFkB activity has long been implicated in the pathogenesis of B-NHL, and our study confirmed that dysregulation of NFkB pathway was main mechanism of lymphomagenesis, providing further rationale that he treatment against malignant lymphoma with inhibitor of NF kappa B pathway.

Description: Abstract 3370 Poster Board III-258 Although the outcome of patients (pts) with adult T-cell leukemia-lymphoma (ATL) remains poor when they are treated with conventional chemotherapy, we previously showed in a multi-center prospective study that one-third of pts who underwent RIST from a related donor in CR or PR could survive without disease for more than 2 years (Tanosaki R et al., BBMT 2008). In this retrospective study, we reviewed our single-center experience with RIST for ATL pts, focusing on the outcome of those who underwent RIST in non-remission status or who relapsed after RIST. A total of 24 pts underwent RIST from a related donor between 2001 and 2008. The median age was 54 years (range, 44-65). Of the 14 males and 10 females, 19 were acute type and 5 were lymphoma type. Disease status at transplantation was 5 CR, 10 PR, 8 NC and 1 PD. Donors were siblings in 18 and children in 6, including 5 HTLV-1 healthy carriers. HLA in serology was 6/6 in 19 and 5/6 in 5. Stem cell sources were PBSC in 22 and BM in 2. Conditioning regimens were fludarabine (30 mg/m2 iv days -8 to -3) and busulfan (3.2 mg/kg iv days -6 and -5) with (n=8) or without (n=16) rabbit anti-T-lymphocyte globulin (ATG, Fresenius; 2.5 mg/kg iv days -2 and -1). All patients received cyclosporine alone for GVHD prophylaxis. Engraftment was rapid in all 24 pts (neutrophil〉500/uL; median 12 days, range 10 -19), with no graft failure. There were 3 non-relapse mortalities; respiratory failure from bronchiolitis obliterans at 21 months (mos), interstitial pneumonitis at 47 mos, and pneumococcal sepsis at 38 mos. Notably, 10 of the 19 pts who were non-CR at RIST survived without disease progression to a median of 53 mos (range, 20 to 85). All of these pts were acute type, and had circulating ATL cells in the peripheral blood (PB) immediately before RIST (average 33% of WBC, range 5-73). Circulating ATL cells decreased to below 5% within 1 mo in 8 pts. A total of 12 pts relapsed within 16 mos; 7 (58%) within 3 mos, and 11 (92%) within 12 mos. Two patients who had relapsed after RIST showed a significant but transient response to the withdrawal of immunosuppression (CR 1, PR 1). Donor lymphocyte infusion was performed in 6 pts without significant benefits. Seven pts who relapsed at a single site, which was confirmed by CT scan or FDG-PET, were treated with local irradiation alone, and 3 whose HTLV-1 proviral load in PB had become negative at relapse survived to 48, 64 and 77 mos; 1 pt required 2 courses of irradiation because of immediate relapse at the margin of the preceding radiation field, and another pt underwent surgical resection of a residual mass since a biopsy revealed a viable lesion at the irradiated site. The 5-year overall and progression-free survival of all pts were 52% (95% CI, 38-66%) and 37% (95% CI, 22-52%), respectively, at a median follow-up of 59 mos (range, 12 to 85) in surviving pts. HTLV-1 proviral load in PB was examined using real-time PCR for tax in 208 samples from 21 evaluable pts, and it became negative at least once in 15 pts (71%), including 1 pt whose donor was an HTVL-1 carrier; proviral load remained negative in 7 pts at a median follow-up of 32 mos (range, 3 to 84). Since HTLV-1 tax is a promising target molecule for identifying the immunological mechanism, HLA-restricted tax-specific CTLs were examined in HLA-A2- and/or A24-positive pts using tax tetramers by taking blood samples periodically after informed consent was obtained from each pt. A total of 80 samples in 13 pts were analyzed. The number of tax tetramer-positive (tax+) cells did not change significantly up to at least 1 year after RIST, while the clinical responses and decrease/disappearance of HTLV-1 proviral load were observed within 3 mos in most cases. An increase in tax+ cells was observed after 1 year in 2 pts who had achieved CR. In conclusion, about half of the acute-type ATL pts with a significant involvement of ATL cells in PB at RIST could survive for a long time in our cohort. ATL pts who relapsed at a single site after RIST still have a chance to be cured with local treatment using irradiation alone or surgical resection with the aid of HTLV-1 proviral load as a marker for minimum residual disease. Since most ATL pts had already become resistant to chemotherapy and the intensity of conditioning was reduced, potent GV-ATL and GV-HTLV-1 effects might have played a key role in disease control. However, tax-specific CTL kinetics did not correlate with either clinical responses or the HTLV-1 proviral load, which suggested that other molecules may be immunologically targeted. Our results might contribute to the establishment of the cure-oriented treatment strategy for ATL pts. Disclosures: No relevant conflicts of interest to declare.

Description: Majority of malignant lymphoma arising from the ocular adnexae are ocular adnexal MALT lymphomas (OAL). Several genetic abnormalities, including t(14;18)(q32;q21), trisomy 18 and trisomy 3 have been reported in OAL. However, none of them are found in more than half of cases with OAL by conventional methods. High density Single Nucleotide Polymorphism (SNP) array analysis with CNAG/AsCNAR algorithm allows high-resolution and genome-wide detection of both loss of heterozygosity (LOH) and copy number abnormality, especially uniparental disomy (UPD), without depending on the availability of paired normal DNA (Yamamoto et al, Am J Hum Genet. 2007; 81:114–26). UPD is acquired by somatic recombination and therefore not detected by conventional cytogenetic analysis or array CGH. In this study we analyzed DNA from OAL for the presence of LOH with or without copy number changes. Tissue samples from patients with OAL at our institute between 1995 and 2003 (N=32) were subject to SNP-array (250K NspI) analysis with CNAG/AsCNAR algorithm. The patients included 21 males and 11 females, and the median age of 56.5 years at the time of diagnosis (range, 15–90 years). Clinical stage was I (29 cases), II (1 case), and IV (2 cases). Trisomy of 3, 18, and 21 were found in 9, 7 and 1 cases, respectively. Overall, LOH due to UPD more than one chromosomal band were found in 16 cases (50%). Recurrent one allele deletion was detected at 6q23-24, 12p13 and 17q21 (N=15, 15 and 21, respectively). In total, 28 (82%) among 32 cases showed one or more of the above changes. Characterization of these recurrent genetic abnormalities might reveal the pathogenesis of OAL.

Description: Abstract 2318 Introduction: ES has been well recognized to increase non-relapse mortality (NRM) in autologous hematopoietic cell transplantation (HCT). However, little information is available on ES in allogeneic HCT, particularly after reduced-intensity conditioning. To determine the incidence, risk factors and outcome of ES after RIST, we retrospectively reviewed the medical records of 285 patients (pts) who underwent RIST at our institution between 1999 and 2007. Patients and Methods: After excluding 37 pts who received cord blood transplantation or a second or subsequent allogeneic HCT, and those who experienced primary graft failure, 248 pts (male 153, female 95) with a median age of 55 y (range, 21–68) fulfilled the criteria of this study. The underlying diagnosis included lymphoma (106 pts; 43%), acute myeloid leukemia (59; 24%), myelodysplastic syndrome (51; 21%), and others (32; 13%). Ninety-two pts (37%) had a standard-risk disease such as acute leukemia or lymphoma in CR1, and 156 (63%) had a high-risk disease. The donor and stem cell source were related PBSC in 170 pts (69%), related BM in 8 (3%), and unrelated BM in 70 (28%). All of the pts received reduced-intensity conditioning with a purine analog and a busulfan-based regimen. With the use of G-CSF after HCT, neutrophil engraftment (ANC ≥500/μ l) was achieved at a median of 12 days (range, 5–28). ES was diagnosed when the patient showed at least 2 of the following symptoms within 96 h of neutrophil engraftment: (1) fever (〉38.0°C) without an identifiable source of infection, (2) skin rash (〉25% of body surface area) that was not due to a drug reaction, (3) weight gain (〉2.5% of baseline body weight), and (4) hypoxia (sPO2

Description: Abstract 270 BACKGROUNDS: A20 (also called TNFAIP3) gene encodes an ubiquitin-modifying enzyme involved in termination of NF-kB responses, and that is negative regulator of NF-kB. We previously reported that A20 is a common genetic target in B-cell lymphomas by using a genome–wide analysis of genetic lesions in 238 B-cell lymphomas. [Kato et al., Nature 459; 712, 2009] In the study, we showed that three Hodgkin's lymphoma (HL)-derived cell lines have deletion of both alleles or loss of one allele and a mutated allele of A20 gene by high-density typing using CNAG/AsCNAR algorism, which enabled accurate determination of allele-specific copy numbers, and thus allowed for sensitive detection of loss of heterozygosity (LOH) without apparent copy-number reduction, even in the presence of up to 70–80% normal cell contamination. Twenty-four primary samples from HL were also analyzed for the mutations and microdissected CD30-positive tumor cells (Hodgkin-Reed-Sternberg (HRS) cells) revealed one intronic and four missense mutations. However, we might have missed the homozygous deletions, which are shown in other B-cell lymphoma subtypes, and underestimates the frequency of involvement of A20 gene in primary HL cases. MATERIALS AND METHODS: The objects were 12 of the 24 samples of our previous cohort. The samples included one case that showed mutation in the previous study. We tried to detect A20 gene deletion in HRS cells with the combination of anti-CD30 immunofluorescence with FISH (fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasm: FICTION) method. BAC clones suitable for FISH analysis of A20 gene were screened. A BAC clone RP11-783B20 (TNFAIP3 locus, 6q23) labeled with spectrum orange by nick translation, was selected because of the best signal/noise ratio. CEP 6 Spectrum Green Probe was used to detect centromere of chromosome 6 (6p11.1-q11). Approximately 4 micrometer thick slides were immunostained with anti-CD30 antibody and FISH was performed. As the diameter of HRS cells is known to be several times more than the 4 micrometer thickness of the section slides suitable for FISH, ratio of A20/CEP 6 signals were calculated and the A20 gene status was evaluated in CD30 positive cells. A20 and CEP6 signals were also counted in CD30 negative cells and used as a control. We counted signals of 30(15–55) CD30 positive cells and 50 CD30 negative cells. RESULTS: In 9 cases among 12 cases, signals were successfully counted. The average number of CEP6 signals on the CD30 negative cells was 1.53, which showed that a whole cell is located on the section slides. The ratio of A20/CEP6 signals on these CD30 negative cells were approximately 1.0 confirming the quality of FISH signals. As predicted, the average number of the CEP6 signals on the HRS cell was approximately 1.21, which suggested that one HRS cell is cut in the middle and divided into pieces during preparation of the section slides. In these CD30 positive cells, the A20/CEP6 ratio was less than 1.0; the cells contained less A20 gene signals than CEP6 signals. The relative numbers of signals determined by FICTION in 9 cases are shown in the table. We knew that the case #3 had A 20 gene mutation determined by direct sequence analysis of micro-dissected CD30 positive cells. As the sequence analysis showed no residual wild A20 genes, the relative ratio of 0.71 was considered as a consequence of loss of normal allele. Thus, the cut-off level of 0.71 was set to define deletion of at least one allele. Two cases showed that the A20/CEP6 signal ratio was more than this figure (0.90 in case #1, and 0.80 in case #4). Except for these 2 cases, 7 out of 9 cases were judged to have deletions of A20 gene. Notably case #6 had the ratio of 0.14, which suggested that virtually complete loss of A20 gene had occurred. The sequence analysis had missed the deletions probably due to the contaminated surrounding cells. CONCLUSIONS: We found a frequent deletion of A20 gene in HL cases including a case with a complete loss. The involvement A20 gene deletion associated with the pathogenesis of HL might be more frequent than previously suggested by the sequence analysis. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 971 NFκB is a tightly regulated transcription factor of lymphocyte activation, proliferation and development. Controlled activity of NF κ B signaling pathway plays critical roles in coordination of immune and inflammatory response. Constitutive NFκB activation is recognized as a key pathological feature in several subsets of B-cell malignant lymphoma, and it is well known that lymphoma frequently occurred in association with chronic inflammation. Recently, our group showed frequent inactivation of A20, a negative regulator of NF κ B, in B-lineage malignant lymphomas. However, the molecular mechanism underlying the aberrant NF κ B activation in lymphomagenesis has not fully understood. In this study, to clarify the genetic basis of the aberrant NFκB activation, we performed genome-wide analysis of copy number alterations as well as allelic imbalances of primary B-lineage lymphoma specimens using Affymetrix GeneChip 250K genomic microarray with the CNAG/AsCNAR algorithm. We also searched for possible mutations in CARD11, CYLD, IKK and TRAF family genes and IκB genes, to obtain comprehensive registry of lesions in genes regulating NFκB pathway. This study included 238 primary lymphoma samples, including 64 samples of diffuse large B-cell lymphomas (DLBCL), 52 of follicular lymphomas (FL), 35 of mantle cell lymphomas (MCL), and 87 of mucosa-associated tissue (MALT) lymphomas. Five Hodgkin lymphoma-derived cell line (KM-H2, L1236, HDLM2, RPMI1666, L540) was also analyzed. Through a genome-wide analysis, we identified that each histology type had a unique genomic signature, suggesting a distinctive underlying molecular pathogenesis for different histology types. In contrast to the fact that A20 mutation was highly associated with loss of heterozygosity at 6q23.3, mutations of CARD11 (5 cases of DLBCL, 2 cases of MALT lymphoma) and IκB family genes (2 cases of DLBCL and 1 cases of MALT lymphoma) had no association with copy number abnormality at the locus of the genes. In total, mutations and copy number alterations in genes regulating NFκB pathway were found in more than 40% of B-cell lymphomas, which underpinned the importance of aberrant NFκB activation in lymphomagenesis. To also assess the role of uncontrolled signaling of NFκB pathway in lymphomagenesis, we re-expressed wild-type A20 in two lymphoma-derived cell lines without normal functional A20 alleles (KM-H2 and L1236). In both cells, re-expression of wild-type A20 resulted in suppression of cell growth and induction of apoptosis, accompanied by down-regulation of NFκB activation. The A20-deficient KM-H2 stably generated tumors in immunodeficient mice, whereas the tumorigenicity was effectively suppressed by re-expression of A20. We further investigated the role of A20 inactivation during clonal expansion of lymphoma by competitive proliferation assays using A20-deficient lymphoma-derived cell lines with or without re-expression of A20. The proportion of A20-expressing cells gradually decreased during competitive cell culture, and A20-expressing cells outgrew control cells in NOG mice, indicating the importance of A20 inactivation in clonal evolution of lymphoma. We demonstrated that uncontrolled NFκB signaling caused by alterations of multiple genes is a common feature of B-lineage lymphomas. Considering the physiological function of NFκB activation induced upon a variety of upstream stimuli, our observations provide an intriguing insight into and the pathogenesis of lymphoma. Our study also indicated that NFκB inhibition may have a role in lymphoma therapeutics. Disclosures: No relevant conflicts of interest to declare.

Description: Background: The management for recurrent lymphoma after allogeneic hematopoietic stem cell transplantation (HSCT) is challenging and it is not clear concerning its outcomes. Since potent graft-versus-lymphoma (GVL) effect is observed in some patients (pts) with follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL) or adult T-cell leukemia/lymphoma (ATL) after allogeneic HSCT using reduced-intensity conditioning (Tanosaki et al, ASH 2006, BBMT2008;14:702), we hypothesized that it could also be exerted in relapsed patients. Hence, we retrospectively analyzed the outcomes among patients with lymphoma who relapsed after allogeneic HSCT. Patients and Methods: Between January 1999 and December 2007, 164 patients with refractory lymphoma, who were deemed incurable with standard or high-dose chemotherapy, underwent allogeneic HSCT in our single institution. Seventy-five pts remain in CR, 33 died associated with non-relapse mortality, 4 were lost follow-up, and 52 pts relapsed after the median of 71 days (range 1–1457), including 1 graft failure. Therefore, 51 pts were analyzed in this study. Results: Histological subtypes were diffuse large B-cell lymphoma (DLBCL) 13, ATL 12, lymphoblastic lymphoma 8, PTCL 7, FL 4, Hodgkin lymphoma (HL) 3, mantle cell lymphoma (MCL) 2, extranodal NK/T-cell lymphoma 2. Ten pts had an early relapse within 30 days, while 41 pts had a systemic (18 pts) or solitary relapse (23 pts) after the median of 98 days (range 33–1457). Relapse-oriented interventions included withdrawal of immunosuppressants (WIS), irradiation or surgical resection of localized lesion, donor lymphocyte infusion (DLI) and chemotherapy, which were used singly or in combination according to the clinical conditions; the breakdown and its outcomes were shown in Table. At the time of relapse, 46 pts (90%) had immunosuppressants, and WIS was first tried in 31 pts who didn’t have GVHD. Overall survival rate (OS) at 2 years after relapse in pts with relapse 〉day 30 and ≤day 30 was 37±8% and 0% (pDay 30     Solitary 23 10 12 2 1 10 (5) 0 11     Systemic 18 15 0 1 1 6 (4) 1 11 Relapse ≤ Day 30 10 6 0 2 2 0 (0) 1 9 Total 51 31 12 5 4 16 (9) 2 31

Description: Background: Ranimustine (MCNU), a derivative of nitrosourea that was developed in Japan, shows good penetration into cerebrospinal fluid and might be expected to decrease CNS relapse of lymphoid malignancies when used before transplantation (Takaue Y, et al. Cancer67:1830, 1991). However, its feasibility and efficacy have not been extensively analyzed in adult patients with lymphoma. Patients and Methods: We retrospectively evaluated an MCEC regimen which consisted of MCNU (200 mg/m2 on days -8 and -3), carboplatin (300 mg/m2 on days -7 through -4), etoposide (500 mg/m2 on days -6 through -4) and cyclophosphamide (50 mg/kg on days -3 and -2) in 68 patients with lymphoma (median age, 48 yr: range, 20–65 yr) who underwent autologous peripheral blood stem cell transplantation (PBSCT) at our institution between January 1999 and February 2008. The diagnosis included diffuse large B-cell lymphoma (n=32), T-cell lymphoma (12), Hodgkin lymphoma (9), follicular lymphoma (14), including 6 transformants, and intravascular lymphoma (1). The median time from diagnosis to PBSCT was 20 months (4–198 mo), and the median number of prior chemotherapy regimens was 3 (2–7). Sixty-six patients (97%) had ECOG PS〈 2, 28 (41%) had prior XRT, 3 (4%) had bulky disease, 42 (62%) had stage III–IV disease, 19 (28%) had IPI at relapse of high (H) or high-intermediate (H-I), and one had IPS 〉4. The disease status at transplantation was 1st CR/PR in 10 (15%), ≥2nd CR/PR in 49 (72%), and NC/PD in 9 (13%). Results: The median number of days to neutrophils〉 500 /μL and platelets〉 20,000 /μL was 10 (8–19) and 10 (4–30), respectively. The platelet count did not decrease below 20,000 /μL in 9 patients. Grade (G) 4 non-hematological toxicities (CTCAE ver. 3.0) included elevated transaminase (1), hyponatremia of 116 mEq/L (1) and hypokalemia of 2.3 mEq/L (1). GI and CNS toxicities consisted of mucositis (G3, n=10), diarrhea (G3, n=27) and seizure (G2, n=1). G1 interstitial pneumonitis was observed in 5 patients. There were no grade 4 cardiac, pulmonary or renal toxicities except for one patient who died of treatment-related multi-organ failure. The cumulative incidence of relapse at 2 yrs was 49 %. Of 33 relapses, 2 occurred newly in the CNS without any previous history. With a median follow-up of 24 months (3–80) after transplantation for surviving patients, the 2-year overall survival (OS) and progression-free survival (PFS) were 68% (95% CI 55–81%) and 50% (95% CI 38–63%), respectively. In univariate analyses, T-cell phenotype (P

Description: Abstract 3508 Background: Allo-HCT is a therapeutic option for patients (pts) with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). However, the outcome of allo-HCT with a reduced-intensity conditioning (RIC) regimen for TL remains controversial, and no previous reports have compared the outcomes after allo-HCT for FL, TL, and DLBCL in the rituximab era. Patients and Methods: We retrospectively analyzed 73 consecutive pts with FL (n=33), TL (n=18), or DLBCL (n=22) who received allo-HCT at our institute between January 2000 and December 2008. We defined TL as DLBCL that was histologically proven in pts with pre- (n=8) or co- (n=10) existing FL. The median age of the 73 pts was 47 years (range, 26–67). The median duration from diagnosis to HCT was 38 months (range, 6–175). The median number of prior chemotherapy regimens was 4 (range, 1–10): 57 pts (78%) had received prior rituximab, and 23 (32%) had received high-dose chemotherapy with autologous HCT prior to allo-HCT. The disease status at allo-HCT was CR or PR/refractory; 23 (32%)/50 (68%) for all pts, 10/23 for FL, 7/11 for TL, and 6/16 for DLBCL. The age-adjusted international prognostic index (aaIPI) at HCT was high or high-intermediate risk in 21 pts (28%), and FLIPI at HCT was high risk in 11 pts with FL (15%). The median level of serum albumin at HCT was 4.2 g/dL (range, 2.7–5.1). A myeloablative conditioning regimen was used for 14 pts (19%), and a RIC regimen was used for 59 pts (81%). The donor and stem cell source were related peripheral blood stem cells in 44 pts (60%), related bone marrow in 2 (3%), unrelated bone marrow in 21 (29%), and cord blood in 6 (8 %). Results: With a median follow-up of 68 months in surviving pts, the 5-year estimated overall survival (OS; Figure) and progression-free survival (PFS) were 58% and 54% for all pts, 80% and 71% for FL, 67% and 67% for TL, and 20% and 17% for DLBCL, respectively. The 5-year cumulative incidences of relapse/disease progression (PD) and non-relapse mortality were 25% and 39% for all pts, 10% and 22% for FL, 24% and 13% for TL, and 50% and 67% for DLBCL, respectively. Grade III-IV acute GVHD occurred in 25% of all pts, and OS was significantly worse in such pts [hazard ratio (HR) 2.5 (95%CI 1.2–5.3), p=0.02]. Extensive chronic GVHD (cGVHD) occurred in 53% of pts who survived 100 days or longer, and OS for patients with extensive cGVHD was significantly worse than that in pts without extensive cGVHD [HR 4.5 (1.3-15.6), p=0.02]. The cause of death included PD in 10 pts, GVHD in 5, infection in 4, non-infectious lung complication in 5, cerebral infarction or hemorrhage in 2, and unknown in 3. No pts with FL died of PD, and no pts with TL who had survived for 7 months after HCT relapsed thereafter. By a multivariate analysis, the OS for DLBCL was significantly worse than that of TL [HR 4.8 (1.7-13.2), p=0.002]. OS for FL was not significantly different from that of TL [HR 0.74 (0.2-2.4), p=0.6]. Other factors that influenced OS were aaIPI at HCT [high or high-intermediate risk, HR 3.7 (1.6-8.5), p=0.002] and the serum albumin level at HCT [

Description: Abstract 3353 Poster Board III-241 [Background] Renal dysfunction is a life-threatening complication after hematopoietic stem cell transplantation, and the incidence of acute and chronic renal dysfunction after non-myeloablative transplantation is reportedly, 40 to 50% and 16 to 35%, respectively. In this study, we evaluated this complication after reduced-intensity stem cell transplantation (RIST) at a single institute. [Patients and Methods] We retrospectively reviewed the medical records of 286 patients (median age, 54 years; range, 21-68) with various hematological disorders who underwent RIST between 1999 and 2007, using a conditioning regimen that consisted of busulfan (oral 8 mg/kg or iv 6.4 mg/kg) and fludarabine (180 mg/m2, n=214) or cladribine (0.66 mg/kg, n=72). Sixty-seven patients also received 2-4 Gy of total body irradiation (TBI). The diagnosis included AML (n=77), ALL (n=9), MDS (n=56), malignant lymphoma (n=116), CML (n=14), and other (n=14). Whereas 188 patients were transplanted from a related donor (BM n=8, PB n=180), 98 were transplanted from an unrelated donor (BM n=80, PB n=1, CB n=17). GVHD prophylaxis consisted of cyclosporine (CSP, starting dose 3 mg/kg/day civ, target whole blood conc. 250-350 ng/ml, n=235) or tacrolimus (starting dose 0.03mg/kg/day civ, target whole blood conc. 10-20 ng/ml, n=51), with (n=131) or without (n=155) methotrexate, and 71 patients also received anti-human T-lymphocyte immunoglobulin (ATG, Fresenius, 5-10 mg/kg). Renal function was assessed in terms of the serum creatinine concentration and the estimated glomerular filtration rate (eGFR) as calculated by the Modification of Diet in Renal Disease equation (MDRD) for our population (eGFR=0.741*175*Age-0.203*Cr-1.154, *0.742, if female). Acute renal failure (ARF) within 100 days was categorized as grade 0 (decrease in eGFR of 25% but