Search

Summary We conducted a randomised phase II study to determine the optimal dose and schedule of melphalan, prednisone, and bortezomib (MPB) (jRCTs031180097). Transplant‐ineligible untreated multiple myeloma patients were randomised to Arm A (twice weekly bortezomib in one six‐week cycle followed by eight five‐week cycles of four times once weekly bortezomib with melphalan and prednisolone on days 1–4) or Arm B (nine four‐week cycles of three times once weekly bortezomib with melphalan and prednisolone on days 1–4). The primary end‐point was complete response (CR) rate. Of 91 patients randomised to two arms, 88 were eligible. The median cumulative bortezomib doses were 45·8 and 35·1 mg/m2, CR rate was 18·6% [95% confidence interval (CI) 8·4–33·4] and 6·7% (95% CI 1·4–18·3), and the median progression‐free survival (PFS) was 2·5 and 1·4 years in Arms A and B [hazard ratio (HR) 1·93 (95% CI 1·09–3·42)], respectively. Frequent grade ≥3 haematologic toxicities in Arms A and B were neutropenia (64·4% vs. 28·3%) and thrombocytopenia (35·6% vs. 10·9%). Grade 2/3 peripheral neuropathy was observed in 24·4/2·2% in Arm A and 8·7/0% in Arm B. In conclusion, Arm A was the more promising regimen, suggesting that the twice weekly schedule of bortezomib in the first cycle and higher cumulative dose of both bortezomib and melphalan influences the efficacy of modified MPB.

Summary Background Standard treatment for untreated advanced-stage follicular lymphoma is rituximab plus chemotherapy. The incidence of histological transformation of follicular lymphoma has been reported only in heterogeneously treated populations and rarely with long-term follow-up. Additionally, the incidence of secondary malignancies after treatment, without high-dose therapy for follicular lymphoma, is largely unknown. The aim of our study was to assess progression-free survival, overall survival, incidence of secondary malignancies, and incidence of histological transformation in a 10-year follow-up analysis of the JCOG0203 trial. Methods In the phase 2–3 randomised JCOG0203 trial, previously untreated patients with stage III or IV indolent B-cell lymphoma, including grades 1–3 follicular lymphoma, from 44 hospital centres in Japan, were randomly assigned (1:1) by use of a minimisation method to receive six cycles of R-CHOP (rituximab [375 mg/m2], given on day 1, plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2, capped at 2·0 mg] given intravenously on day 3, and oral prednisone [100 mg once daily on days 3–7]) every 3 weeks (R-CHOP-21) or every 2 weeks (enabled by mandatory granulocyte-colony stimulating factor administration once daily for 6 days, starting on day 8; R-CHOP-14) without rituximab maintenance. Age, bulky disease (nodal or extranodal mass ≥10 cm in diameter on CT), and institution were used as adjustment factors. Investigators enrolled participants, and assignment to trial groups was done with a computer-assisted randomisation allocation sequence that took place centrally at the Japan Clinical Oncology Group Data Center, without the intervention of investigators. Interventions were not masked for patients or investigators. Data were collected 10 years after enrolment of the last patient. The primary endpoint of the phase 3 part of the study was progression-free survival, and the primary endpoint of the phase 2 part of the study was the proportion of patients who achieved a complete response. Accrual was 4·5 years, and follow-up was 3 years after registration was closed. Data were updated on the cutoff date of Feb 28, 2017. Intention-to-treat analyses (ie, progression-free survival, overall survival, and incidence of secondary malignancies) were predefined, to be done at 10 years after the last patient was enrolled. An additional analysis of the incidence of histological transformation was defined 15 years after the protocol, on May 8, 2017, in a supplementary analysis plan, and assessed at 10 years after the last patient was enrolled. Follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00147121. Findings Between Sept 1, 2002, and Feb 28, 2007, 300 patients were enrolled, and 149 (50%) were assigned to the R-CHOP-21 group and 151 (50%) were assigned to the R-CHOP-14 group. After eligibility was assessed, one patient was excluded from the R-CHOP-21 group. 10-year progression-free survival was not different between groups (R-CHOP-21 33%, 95% CI 25–41; R-CHOP-14 39%, 31–47; hazard ratio 0·89, 95% CI 0·67–1·17). In 248 patients with grade 1–3a follicular lymphoma, progression-free survival was 39% (33–45) at 8 years and 36% (30–42) at 10 years. The cumulative incidence of histological transformation was 3·2% (95% CI 1·5–6·0) at 5 years, 8·5% (5·4–12·4) at 8 years, and 9·3% (6·1–13·4) at 10 years after enrolment. At 10 years, the cumulative incidence of secondary malignancies was 8·1% (5·1–12·0) and the cumulative incidence of haematological secondary malignancies was 2·9% (1·3–5·5). Interpretation R-CHOP is a viable option for first-line treatment in patients with newly diagnosed advanced follicular lymphoma. Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death. Funding National Cancer Center and Ministry of Health, Labour and Welfare of Japan.

The clinical features and prognostic significance of myeloma cells containing granules remain unclear. The purpose of this retrospective study was to investigate the clinical significance of granule‐containing myeloma cells in patients with newly diagnosed multiple myeloma (NDMM). We retrospectively analyzed the records of 122 patients diagnosed with NDMM between January 2007 and December 2013. Granule‐containing myeloma cells were defined as myeloma cells that exhibited three or more granules in their cytoplasm by May‐Giemsa staining. The patients were classified into two groups, the granule‐containing myeloma (GM) and nongranule‐containing myeloma (non‐GM) groups, depending on the proportion of myeloma cells that contained granules (cut‐off value: 10%). There were 25 (20.5%) patients in the GM group. Patients in the GM group displayed significantly higher CD56 and CD49e expression than those in the non‐GM group (t‐test, P = 0.027 and 0.042). None of the patient characteristics differed significantly between the two groups. There was no significant difference in the chemotherapy profiles of the two groups, and the overall response rates of the two groups were similar. During the median follow‐up period of 33.9 months, the overall survival (OS) in the GM group was similar to that in the non‐GM group; 4‐year OS of the GM and non‐GM groups were 78.5% and 51.9%, respectively (P = 0.126). We concluded that cases of NDMM involving granule‐containing myeloma cells are not infrequent. Moreover, CD56 and CD49e expression was significantly higher in the presence of myeloma cell populations, and the presence of granules did not affect survival.

Cancer-related fatigue (CRF) is one of the adverse events in multiple myeloma (MM) patients treated with cytotoxic agents, proteasome inhibitors (PIs), and immunomodulatory drugs (IMiDs) such as bortezomib, lenalidomide, and thalidomide. The aims of our study were to prospectively analyze the clinical significance of CRF, and to evaluate the cumulative incidence of CRF and the survival rates of 16 MM patients who were treated with PIs and IMiDs. Reactivation of salivary human herpes virus (HHV)-6 and HHV-7 was analyzed using real-time quantitative polymerase chain reaction (qPCR). CRF was evaluated using a visual analog scale (VAS). Eleven newly diagnosed multiple myeloma (NDMM) and five relapsed or refractory MM patients were enrolled in this study. The cumulative incidence of CRF was 54.9%. The treatment types were not associated with the CRF incidence. The cumulative incidence of reactivation of HHV-6 and HHV-7 was 73.1% and 45.6%, respectively. However, the reactivation of HHV-6 and HHV-7 was not related to CRF. The overall survival (OS) and progression-free survival (PFS) in NDMM patients with CRF was significantly shorter than in those without CRF. In conclusion, CRF was one of the major symptoms in MM patients, and predicted shorter OS and PFS in NDMM patients.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) sometimes occur following Anti-thymocyte globulin (ATG) administration for allogenic stem cell transplantation but are rare in aplastic anemia (AA) patients. A 55-year-old woman with AA following ATG developed refractory fever and was diagnosed with EBV-LPD. She was successfully treated with weekly rituximab monotherapy; however, she developed EBV encephalitis. She was admitted to the intensive care unit and finally recovered from unconsciousness. EBV-LPD should be considered after ATG for AA when symptoms appear. Because EBV-LPD following ATG for AA can rapidly progress, weekly monitoring of EBV-DNA and early intervention may be necessary.

Although anti-T lymphocyte globulin-Fresenius (ATG-F) is commonly used as prophylaxis for graft-versus-host disease (GVHD), the appropriate dosage of ATG-F in the setting of a reduced-intensity conditioning (RIC) regimen has not been determined. In the present study, we retrospectively analyzed the clinical outcomes of 103 patients after unrelated bone marrow transplant (uBMT) with RIC regimens. RIC regimens consisted of purine analogue plus busulfan with low-dose TBI or ATG-F (5–10 mg/kg in total). Median age was 57 years (range 20–68). The incidence of grade II–IV acute GVHD and chronic GVHD with ATG-F was significantly lower than that with TBI 2 Gy (15 vs. 61 %, P < 0.05; 33 vs. 57 %, P < 0.05). The incidence of 2-year NRM with ATG-F was significantly lower than that with TBI 2 Gy (6 vs. 28 %, P < 0.05). There was no statistically significant difference in the cumulative incidence of 2-year relapse between the ATG-F and TBI 2 Gy groups (37 vs. 20 %, P = 0.13). In conclusion, the addition of low-dose ATG-F to GVHD prophylaxis in patients who received uBMT resulted in decreased incidence of acute and chronic GVHD, which led to a significantly reduced risk of NRM without compromising overall survival. The beneficial effect of low-dose ATG-F should be assessed in a prospective clinical trial.

A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III-IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.

e256 Our results demonstrate different immune and hormonal abnormalities in MM patient’s. We have focused attention on differences in male and female patients. Immune response in women tend to be more vigorous .CD3+,CD4+,CD19+ and NK-cells are lower in female patients than in males. In men decreased FSH, LH and significantly decreased T/E2 ratio with increased E2 and cortisol concentrations were found. Female patients with multiple myeloma demonstrated normal values of FSH, LH ,but a diminished E level and T/E2 ratio, with significantly elevated cortisol level. Conclusion: a significant cellular imuune dysfunction and hormonal imbalances were found in multiple myeloma patients. Which will improve the approaches of MM patients according to gender and facilitate the introduction and optimization of novel immunotherapeutic and hormonal agents.

Background: Oral tacrolimus (Tac) was first developed as a twice-daily formulation (Tac BID) and has been widely used in solid organ and allogeneic hematopoietic stem cell transplantation (allo-SCT). Lifelong immunosuppression is required to preserve graft function after solid organ transplantation, and medical nonadherence of transplant recipients has been identified as a major cause of allograft failure. It has been well documented that frequent drug dosing affects patients' adherence. In response to this potential nonadherence problem, a once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed. Results of randomized prospective phase III studies have indicated that Tac QD is well tolerated with similar efficacy and safety profiles as those of Tac BID in recipients after organ transplantation. Although Tac BID has been widely used in allo-SCT recipients, there are no available data on the use of Tac QD in this population. In this study, we compared retrospectively the efficacy of Tac QD versus Tac BID administration. The objective of this study was to investigate whether Tac QD is as effective as Tac BID in the setting of allo-SCT from unrelated donors. Methods: The study cohort included 77 consecutive patients who received allogeneic bone marrow transplantation from unrelated donors for treatment of hematologic malignancies between 2000 and 2014: AML (n=35), ALL (n=15), CML (n=8), MDS (n=12), NHL (n=5), and MPN (n=2). Patients received Tac iv from day -1 with short-term methotrexate (MTX) on days 1, 3, 6, and 11; Tac iv was converted to either Tac QD (n=37) or Tac BID (n=40) when the patients were engrafted and could tolerate oral medication. Doses were modified to maintain a whole-blood trough concentration of 8-12 ng/ml. Tac BID was administrated until Oct 2008, and Tac QD was used from Nov 2008. Kaplan-Meier estimates were used for overall survival (OS), and cumulative incidence estimates were used for acute GVHD, chronic GVHD, and non-relapse mortality (NRM). Results: Median age was 53 years (range: 23-66) for Tac QD cohorts and 39 years (range: 17-56) for Tac BID cohorts. Tac QD patients were older (P Conclusions: Although Tac QD cohorts included older patients than Tac BID cohorts, there was no difference in the risk of acute GVHD or chronic GVHD between Tac QD cohorts and BID cohorts. As Tac QD possibly contributes to reducing physical and mental stress for patients who need to take several different medications, our findings may indicate that the use of Tac QD for GVHD prophylaxis is beneficial for patients undergoing allo-SCT from unrelated donors. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Background: The use of imatinib in combination with chemotherapy has increased a complete remission (CR) rate and allows to receive allogeneic hematopoietic cell transplantation (HCT) for the patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL). HCT is the standard of care for the eligible patients with Ph + ALL in first CR. We hypothesized that an intensified pre-transplant conditioning regimen might improve the outcome. The aim of this study was to assess the efficacy and safety of intensified conditioning regimen for the Ph + ALL patients who received imatinib-containing chemotherapy before HCT. Methods: We retrospectively analyzed the data of 12 patients with Ph + ALL in the first CR who underwent HCT in our hospital between 2003 and 2012. An intensified conditioning regimen consisted of total body irradiation (TBI) 10 Gy administered in 5 fractions, ETP 60mg/kg, and CY 120mg/kg. Results: The median time from achievement of CR to HCT was 4.1 months (range, 1.4-7.4 months). The median age at the time of HCT was 40 years (range, 30-52 years). Donors were related bone marrow or peripheral blood (n = 4), unrelated bone marrow (n = 5) or umbilical cord blood (n = 3). With a median follow-up of 4.3 years (range, 1.1-10.1 years), the probability of overall survival, relapse, and non-relapse mortality at 4 years were 91%, 18%, and 0%, respectively. All of the 7 patients who achieved molecular remission at the time of HCT remained alive in CR, whereas 2 of 5 patients who did not achieve molecular remission had relapse after HCT. Conclusions: Our results suggest that TBI and CY plus ETP might be a feasible and effective conditioning regimen for the Ph + ALL patients in the imatinib era, especially if the patients obtained molecular remission before HCT.

Abstract 4342 (Purpose) We retrospectively analyzed the data regarding patients who received fractionated administration (FR) of gemtuzumab ozogamicin (GO) and standard administration (ST) of GO for the treatment of their refractory and relapsed acute myeloid leukemia in order to review the efficacy and safety of GO in each type of administration. (Method) The patients with relapsed and refractory acute myeloid leukemia (excluding patients with acute promyelocytic leukemia) who were treated with the ST of GO received 2 doses of monotherapy with 9 mg/m2 GO as a 2-hour intravenous (iv) infusion with a 14–28-day interval. The fractionated GO group received 2 doses of GO monotherapy administered as a 2-hour iv infusion of 3 mg/(m2·day) on days 1, 3, and 5 with a 14–28-day interval. (Result) Eleven patients received ST and 9 received FR. The median age of all patients was 66.1 (55–77) years. Overall response rates (CR+CRp) in the ST and FR groups were 27% and 33%, respectively. The adverse events (grade 3–4) in the ST and FR groups were neutropenia (100% vs. 100%), thrombocytopenia (90.9% vs. 88.9%), and hypertransaminasis (18.2% vs. 0%). Grade 3–4 hypertransaminasis was seen only in the ST group. Infusion reactions occurred in 5 patients: 3 in the ST group and 2 in the FR group. The median CD33 positivity of blast cells of patients who received CR or CRp was 90.9% (78.2–99.5%). (Discussion) The response rates of the ST and FR groups were similar. However, the incidence of grade 3–4 hypertransaminasis tended to be higher in the ST group. These data suggest that FR of GO is less toxic than ST. Thus, FR of GO is safer than ST even for Japanese patients with acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.

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 Results: Among the 248 pts, 45 (18%) developed ES at a median of 14 days (6-23) after allogeneic HCT. Symptoms consisted of fever (100%), skin rash (53%), weight gain (62%) and hypoxia (33%). The incidence of ES in recipients of unrelated donor grafts was significantly higher than that in recipients of related donor grafts (28% vs 14%, p=0.02), and male pts had a significantly higher incidence of ES than female pts (22% vs 12%, p=0.04). No significant difference in the incidence of ES was observed between groups stratified according to age, stem cell source, TNC or CD34+ cell dose, disease risk, GVHD prophylaxis, and the timing of engraftment. By a multivariate analysis, use of an unrelated donor (HR 2.3, 95%CI 1.3–4.1, p=0.007), pts with lymphoid malignancy (HR 2.0, 95%CI 1.1–3.7, p=0.03) and male pts (HR 2.0, 95%CI 1.0–4.0, p=0.04) were associated with a significantly increased risk of ES. Among the 40 pts who required systemic corticosteroid therapy, 31 (78%) achieved a complete response, and the remaining 9 (23%) responded partially. There was a trend toward a higher incidence of grade III-IV acute GVHD (27% vs 18%, p=0.10) in pts with ES, and the incidence of extensive chronic GVHD (69% vs 62%, p=0.04) was significantly higher in pts with ES. Overall survival (OS) and non-relapse mortality (NRM) were not significantly different between the two groups, after a median follow-up of 53 months (range, 2–108) in surviving patents. A multivariate analysis showed that pts with high-risk disease (NRM, HR 1.9, 95%CI 1.1–3.3, p=0.01; OS, HR 2.5, 95%CI 1.6–3.8, p Conclusions: ES is a rather common complication after RIST, especially in recipients of unrelated donor grafts. Although ES shows an initial good response to corticosteroid therapy, ES may have a negative impact on survival, especially in pts with standard-risk disease, and this effect may be related to the occurrence of GVHD. The development of an optimal treatment for ES may improve the outcome of pts who have received RIST by reducing GVHD-related mortality. Disclosures: No relevant conflicts of interest to declare.

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 [ Conclusion: In the rituximab era, pts with TL showed more favorable outcomes after allo-HCT compared to those with DLBCL, and there was no significant difference in OS between FL and TL. AaIPI and the serum albumin level at HCT may be useful surrogate markers that influence OS for pts with B-NHL after allo-HCT. Allo-HCT, mainly with the use of a RIC regimen, might be a promising option for pts with relapsed or refractory FL and TL. Disclosures: No relevant conflicts of interest to declare.

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 [Results] The median follow-up in surviving patients was 746 days (87-3291). The numbers of patients who developed grade 1, 2 and 3 ARF were 139, 72 and 9, respectively. The cumulative incidence of grade 2-3 ARF was 29 % at 100 days after RIST. The overall survival was significantly better in patients with grade 0-1 ARF than in those with grade 2-3 ARF (62% vs 42% at 2 years, p [Conslusion] We found that ARF was significantly associated with a higher mortality after busulfan-based RIST, and that preceding grade 2-3 ARF led to the occurrence of CKD in surviving patients, which highlights the importance of preventing ARF. This study also indicated that the incidence of acute and chronic renal complications was lower in our population compared to previously reported data from Western countries. Therefore, ethnicity should be taken into account when designing future international clinical trials. Disclosures: No relevant conflicts of interest to declare.