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Abstract 2072 Poster Board II-49 Backgrounds Currently, there are many efforts to design risk-adapted strategies in newly diagnosed acute promyelocytic leukemia (APL) by modulating treatment intensity and those seem to be an efficient approach to minimize treatment-related morbidity and mortality (TRM) while maintain the potential in cure for each relapse-risk group. We had postulated that maintaining of Ara-C during induction therapy might have acceptable toxicities yet obtaining good CR in newly diagnosed APL, and idarubicin alone during consolidation periods might have excellent LFS and OS with low relapse rate. Patients and Methods Eighty six patients with newly diagnosed APL were enrolled in the “multicenter AML-2000 trial” after informed consents were obtained during the period of January 2000 to July 2007. For remission induction therapy, patients received oral ATRA (45mg/m2/d, maintained until CR) combined with idarubicin (12mg/m2/d, D1-D3) plus Ara-C (100mg/m2/d, D1-D7). After CR achievement, patients received 3 monthly consolidation courses consisting of idarubicin (12mg/m2/d, D1-D3) alone and maintenance therapy with ATRA (45mg/m2/d, D1-D15, every 2 month) alone had continued for 2 years. Total patients were divided into low-risk, intermediate-risk and high-risk groups according to a predictive model for relapse risk (Sanz score) based on pretreatment WBC and platelet count and the treatment outcomes were compared in the different risk groups. Results The median age of our cohort was 40 years old (range; 6-80) and median follow-up was 27 months (range; 1-90). The distribution of patients in the 3 risk groups was as follows ; 28 (32.6%) patients in low-risk, 40 (46.5%) in intermediate-risk and 18 (20.9%) in high-risk. Overall, CR was achieved in 78 (90.7%) of 86 patients. The CR rate according risk groups was 96.4% in low-risk, 87.5% in intermediate-risk, and 88.9% in high-risk group and there was no significant statistical difference among the different risk groups. During induction therapy, 48 (55.8%) patients experienced grade 3-4 treatment-related toxicity (TRT), mostly fever and infection (38.8% of all patients) and 6 (7.0%) patients died of treatment-related complications. During 3 consolidation courses, 25 (29.1%) of 78 patients experienced grade 3-4 TRT in 1st course, 27 (36.0%) of 75 patients in 2nd course, and 14 (28.0%) of 50 patients in 3rd course. Overall, 3 (3.5%) patients died of treatment-related complications in CR. The incidence of TRT and treatment-related mortality (TRM) during induction or consolidation therapy showed no significant statistical difference among the different risk groups. The relapse occurred in 6 (7.0%) patients; 2 cases in intermediate-risk and 4 cases in high-risk. However, none had relapsed in low risk group, 5 patients of relapsed patients relapsed during consolidation courses and only one patient, however, relapsed during maintenance therapy. The overall survival (OS) and leukemia-free survival (LFS) rate at 7 years in all of patients was 76.7% and 83.5%, respectively. The OS rate at 7 years was 92.9% in low-risk, 78.6% in intermediate-risk and 53.6% in high-risk group (P:0.04) and the LFS rate at 7 years was 96.4%, 83.4% and 62.2% respectively, showing the significant difference between 3 different risk groups (P:0.046). Conclusions This study indicates that our protocol composed of induction therapy with “3+7” chemotherapy plus ATRA followed by consolidations with three courses of idarubicin alone and maintenance therapy with ATRA alone yields a high CR rate and low relapse rate but minimal acceptable toxicities. Despite of adding Ara-C during induction therapy, we did not find much significant toxicities but having good CR rates, and despite of not adding any additional low/intermediate dose chemotherapies(ie, 6MP), we were able to observe significantly high relapse rate in low and intermediate risk group with excellent LFS and OS. Meanwhile, in high-risk group, the relapse rate was significantly higher than other risk groups and most of the relapses occurred in the middle of consolidation courses. This data suggests that our consolidation therapy composed of anthracycline alone may be not enough to minimize risk of relapse in high-risk group in contrast with the low and intermediate-risk groups. More intensive consolidation therapy combined with other effective, but get tolerable chemotherapies or hematopoietic stem cell transplantation in first CR or the combination of arsenic trioxide or others in front-line therapy should be considered in the patients with high-risk of relapse. Disclosures: No relevant conflicts of interest to declare.

Background: Autologous peripheral blood stem cell transplantation (PBSCT) has been used as a major treatment strateg for malignant lymphoproliferative disorder. The number of CD34 positive cells in the harvested product is a very important factor for achieving successful transplantation. We studied the factors that can predict the number of CD34 positive cells in the harvested product of multiple myeloma (MM) and Non-Hodgkin's lymphoma (NHL) patients after mobilizing them with chemotherapy plus G-CSF. Methods: A total of 69 patients (MM 25 patients, NHL 44 patients) with malignant lymphoproliferative disorder had been mobilizedwith chemotherapy and granulocyte colony-stimulating growth factor from January, 2003 to July, 2008. We analyzed the clinical characteristics, the peripheral blood (PB) parameters and the number of CD34 positve cells in the PB and their correlation with the yield of PBPCs collected from the mobilized patients. Results: The total number of leukapheresis sessions was 134 (mean: 1.94 session per patient), and the mean number of harvested CD34 positive cell per patient was /kg. The number of harvested CD34 positive cells was correlated with the patient's height, the number of peripheral blood hematopoietic progenitor cells (HPC) and the number of PB CD34 positive cells at the harvest (P＜0.05). But the number of PB CD34 positive cell was the only significant factor for the quantity of harvested CD34 positive cells on the linear regression analysis (P＜0.05). More than 23.7/ PB CD34 positive cells were needed to harvest /kg CD34 positive cells, according to the ROC curve (P＜0.05).Conclusion: The number of PB CD34 positive cells (23.7/) at the harvest might be the predictor of harvesting more than /kg CD34 positive cell for autologous PBSCT in patients with malignant lymphoproliferative disorder.

Cytogenetics is still being considered the most powerful single prognostic factor, which is useful to determine the types of post-remission therapy in AML, though various molecular markers are available for predicting the prognosis of AML patients. Most phase III studies have failed to demonstrate a clear advantage of allografting over chemotherapy in terms of overall survival because of significant risk of transplant-related mortality. Optimal post-remission therapies in terms of frequencies (number of treatment) or intensities are not decided yet. In this study, since 2000, we investigated that outcomes of post-remission therapies(high-dose cytarabine (HDAC) vs autologous stem cell transplantation (AutoSCT) vs allogeneic stem cell transplantation from sibling or unrelated donors (AlloSCT)) based on cytogenetic risk (GPG, Good prognosis group; IPG, Intermediate prognosis group; PPG, Poor prognosis group by MRC definition) on the AML patients who achieved complete remission after induction chemotherapy. The aims of this prospective intention to treat analysis was to compare the CR, recovery kinetics, DFS and OS in the different prognostic groups. Three plus seven (idarubicin 12mg/m2, D1–D3; cytarabine 100mg/m2, D1–D7) were given to de novo AML, secondary AML and therapy-related AML. Then, HDAC or AutoSCT was given after intermediate dose (8gm/m2) of cytarabine to the patients with GPG. Three times of post-remission therapy including HDAC, or AutoSCT followed by two times of post-remission therapy were given to IPG or PPG. If HLA-identical sibling was available, then AlloSCT underwent after 1st post-remission therapy. Since January, 2000, 506 patients(18 centers) were enrolled up to December, 2007. Among them, 92.3% was de novo AML, and GPG, IPG and PPG were, 23.1%, 62.1% and 14.8% respectively. Over all complete remission rate after 1st induction was 79.0% and CR rate in GPG, IPG, PPG were 92.0%, 81.0% and 43.9% respectively(P

We identified the clinical characteristics including disease status for expecting success outcome of empirical antifungal therapy for invasive fungal infection (IFI) using itraconazole in immunocompromised patients with hematological malignancies. The prospective multicenter observational study was performed at 26 medical centers for 9 months. Three hundred seventy six patients with hematological malignancies (median age 48) had been enrolled and analyzed. The patients with possible and probable categories for IFI according to the EORTC/MSG criteria were included. We excluded the patients with proven IFI. IV itraconazole was administered as routine schedule. Oral itraconazole solution was used after the IV itraconazole. Underlying disease consisted of 61% of AML and 15% of ALL. Overall success rate of empirical antifungal therapy with itraconazole was 196/376 (51%). Acute leukemia in non-CR status and advanced stage of MDS patients showed a lower trend of success rate. Combined co-morbidities, underlying lung disease, poor ECOG performance status (≥2), abnormal chest X-ray at the time of initiation of empirical antifungal therapy, no early initiation of empirical antifungal therapy (the duration of baseline neutropenic fever ≥3 days) and antifungal prophylaxis other than itraconazole were associated with decreased overall success rate. Multivariate analysis revealed that poor ECOG performance status (≥2) (P=0.01, HR = 1.90, 95% CI 1.17–3.06) and abnormal chest X-ray (P=0.02, HR = 2.00, 95% CI 1.12–3.58) were significantly associated with poor outcome of empirical antifungal therapy with itraconazole. Overall success rate of empirical antifungal therapy was not affected by antifungal prophylaxis. Defervescence in setting of neutropenia was 70% (264/276). Higher rate of defervescence was observed in the patients with early stage of MDS (92% vs. 40%, P = 0.02). Median time to defervescence after empirical itraconazole therapy was 3 days. Short mean time to defervescence was observed in the patients with acute leukemia in CR status (P = 0.002) or early stage of lymphoid malignancies (P = 0.03). Baseline fungal infections were diagnosed in 13 patients (3%). Of the patients with baseline fungal infections, 7 patients (54%) had a successful outcome. All 7 patients with successful outcome had baseline fungal infection with candidemia. The rate of breakthrough fungal infection was 4% (16/376). Breakthrough aspergillus infection was documented in the half of theses patients (8/16). The rate of breakthrough fungal infection also was not different according to the different disease status. Premature discontinuation of itraconazole therapy because of toxicity or lack of efficacy occurred in 35% (131/376). The proportion of patients who survived for at least 7 days after completion of itraconazole therapy was 90% (338/376). IV itraconazole followed by oral itraconazole solution is an effective regimen for empirical antifungal therapy in the haematological malignancy patients with persistent neutropenic fever. Poor performance status and abnormal chest X-ray were predictive factors for failure of empirical antifungal therapy with itraconazole in the patients with hematological malignancies. Table 1. Outcomes (overall success rate) according to the clinical characteristics Yes No P Co-morbidities 37/90 (41%) 156/286 (55%) 0.03 Diabetes mellitus 6/20 (30%) 187/356 (53%) 0.07 Lung disease 3/14 (21%) 190/362 (53%) 0.03 ECOG performance status -≥2 (vs. 0 or 1) 45/123 (37%) 148/253 (59%) < 0.001 Galactomannan test – positive 3/9 (33%) 33/74 (45%) 0.73 Abnormal chest X-ray 23/70 (33%) 156/278 (56%) 0.001 Abnormal chest CT 14/51 (28%) 5/8 (63%) 0.10 Duration of baseline neutropenia ≥7 days (vs. 10 days (vs. ≤10 days) 60/122 (49%) 133/254 (52%) 0.58 Duration of baseline neutropenic fever ≥3 days (vs.

Introduction: Central nervous system (CNS) involvement in patients with diffuse large B-cell lymphoma (DLBCL) is a serious complication with a poor prognosis. Secondary CNS involvements in DLBCL are divided into 2 types as follows: CNS involvement at the time of systemic relapse or progression, and isolated CNS relapse despite systemic remission. The frequency of secondary CNS involvement is reported as variable from 4% to 27% in patients with DLBCL who did not receive CNS prophylaxis. However, there is no clear consensus as to the subset of DLBCL benefits from CNS-directed preventive therapy. Furthermore, there is no general agreement on the intensity and type of therapy against secondary CNS involvement. Thus, we analyzed the clinical features and treatment outcomes of secondary CNS involvement in patients with DLBCL. Patients and methods: We analyzed 59 patients who diagnosed with DLBCL and had secondary CNS involvement. Secondary CNS involvement was defined as a brain parenchyma lesion or leptomeningeal involvement or combined during the follow-up or during the treatment. Results: 35 patients were initially treated with CHOP or CHOP-like regimens, and 24 patients with rituximab-CHOP (R-CHOP). The median age of the patients was 54 years old (range 17–77). 37 patients (62.7%) were presented as advanced stage (7 patients with stage III, 30 patients with stage IV), and 40 patients showed elevated serum LDH. Thus, 27 patients belonged to the high-intermediate or high risk of international prognostic index (IPI). The pattern of CNS involvement was as follows: 21 had lesions of brain parenchyma, 30 leptomeningeal involvements, and 8 combined lesions. There was no clinical variable predicting a pattern of CNS involvement. We dichotomized the patients based on the onset of CNS involvement: early CNS involvement occurred within one year from diagnosis (Early CNS group, 42 patients) and delayed CNS involvement after one year (Delayed CNS group, 17 patients). The early CNS group had more advanced stage of patients (26 patients with stage IV) than delayed CNS group (4 patients with stage IV). The presence of bone marrow invasion was also significantly associated with early CNS involvement: 18 patients in early CNS involvement and 1 patient in delayed CNS involvement. In addition, high or high-intermediate risk of IPI was related with early CNS involvement (P < 0.05). The response to the primary treatment against DLBCL was not related with the onset of CNS involvement, thus 46 patients showed objective response including 33 complete responses (CR). The use of rituximab was not associated with the onset of CNS involvement. However, the number of patients with partial response (PR) was higher in the early group (9/46, 19.6%) than delayed CNS group (2/17, 11.7%). Thus, these findings suggest patients with high tumor burden represented by advanced stage, high IPI, and bone marrow invasion might have CNS involvement at the time of diagnosis. However, the overall survival was not significantly different between these two groups, and the median overall survival of patients with secondary CNS involvement was 5.13 months (95% confidence interval: 3.39–6.87 months). When we compared survival based on the type of therapy in patients with isolated brain parenchyma involvement, combined treatment approach including systemic chemotherapy (high-dosage methotreaxate (MTX) chemotherapy) and localized therapy (intrathecal MTX chemotherapy and/or whole brain radiotherapy) showed a tendency of better survival than localized therapy alone. However, the addition of systemic chemotherapy was not translated into survival benefit in patients with isolated leptomeningeal CNS involvement. Furthermore, the role of systemic chemotherapy using high-dosage MTX was not proved in patients with systemic disease progression and secondary CNS involvement although it showed the tendency of better survival. Conclusions: Patients with advanced stage, high or high-intermediate risk of IPI, and the presence of bone marrow invasion might have a high risk of secondary CNS involvement even during the active treatment. Thus, CNS prophylaxis should be considered. However, further prospective study should be warranted to determine the intensity and type of treatment against secondary CNS involvement in DLBCL.

Backgound; Although allogeneic hematopoietic stem cell transplantation (alloSCT) from matched related donor (MRD) is a standard therapy for severe acquired aplastic anemia (AA), alternative donor (AD) alloSCT is increasing and the survival of alloSCT from AD improves nowadays. Aims: We planned this study to review the recent result of alloSCT survival and to compare AD with MRD. Methods: A retrospective study comparing MRD and AD for alloSCT in patients with AA was conducted by Korean Society of Blood and Marrow Transplantation (KSBMT2007-02 study). Results: The patient population was AA, pure red cell aplasia, paroxysmal nocturnal hemoglobinuria, and they underwent alloHSCT from 1997 and 2007. Total 336 patients were enrolled in 24 Korean alloSCT centers. Survival analysis was done in 331 patients because data were not available in 5 patients. Two hundred five adult patients with AA were also analyzed to define the characteristics of adult AA patients. AA was 97.3% and median age at alloSCT was 20.4 (1–62) years old. Median time from diagnosis to alloSCT was 6.2 (0.2–248.4) months. Male was 48.9%. Seventy nine percent patients received bone marrow (BM) as a stem cell source. AD had longer time from diagnosis to alloSCT (p=0.049) and received more peripheral blood (PB) or cord blood (CB) as a stem cell source (16.3% vs. 31.7%, p=0.004). Univeriate analysis showed MSD (p Summary: In conclusion, our study showed that donor type was not a significant factor for survival. Therefore, AD should be considered earlier when there is no MRD in patients with AA.

Peripheral T cell lymphoma (PTCL) is a heterogenous group of aggressive lymphoma, which T-cell phenotype itself associated with unfavorable prognostic factors when compare to patients with B-cell phenotype lymphoma. High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) has represented a rescue option from poor prognosis. We retrospectively investigated the clinical outcomes of ASCT in 139 Korean patients with PTCL between December 1994 and June 2007. The overall survival (OS) and progression-free survival (PFS) were measured from the date of transplantation and were estimated using the Kaplan-Meier method. The median age at transplantation was 41 years. The histological subtypes had 45.3% PTCL-unspecified, 13.7% anaplastic large cell (ALK +/−: 15.7/57.8%), 10.8% angioimmunoblastic T cell, 21.6% extranodal NK/T cell, and 8.6% others. Disease status at transplantation consisted of 54 patients (38.8%) with first complete response (CR)/partial response (PR), 58 patients (41.7%) with chemosensitive-relapsed CR/PR, 15 patients (10.8%) with refractory CR/PR and 12 patients (8.6%) with progressive or refractory. At a median follow-up of 29.3 months, the 5-year probability of OS and PFS was 42.3±4.9% and 42.2±5.9%, respectively. The 5-year OS and PFS rates in patients with 1st CR/PR were 64.9±7.2% and 61.1±7.6%, compared to those in patients with chemosensitive-relapsed and refractory CR/PR were 33.5±6.8% and 33.2±8.3%, respectively. Early transplant-related mortality was 10.1%. Histological subtypes, bulky (≥10cm), prognostic index for PTCL (PIT) at diagnosis (0–2 vs 3–4), age-adjusted IPI at diagnosis, disease status at transplantation, the transplant timing (front-line vs second-line) and conditioning regimen were significant differences of survivals in univariate analysis. PIT, the transplant timing and the achievement of CR before transplantation were the variable prognostic for OS and PIT, bulky, and the achievement of CR provided significant independent factors for PFS in multivariate analysis. Our data showed that patients with PTCL who had low PIT and achieved CR before ASCT improved the OS and PFS regardless of the transplant timing and front-line ASCT of primary chemosensitive patients was effective in the OS. Figure Figure

Aplastic anemia (AA) and pure red cell aplasia (PRCA) seems more frequent in Asian countries including Korea. However, there is no exact data regarding its prevalence and frequency of allogeneic hematopoietic stem cell transplantation (HSCT) in Korea. Here we present the demographic data of AA/PRCA in Korea. Data were prepared by retrieving computerized database of National Health Insurance Corporation and Korea National Statistical Office. HSCT data were collected from all HSCT centers in Korea through Korea Hematopoietic Stem Cell Transplantation Nurses’ Society. The selection criteria of PRCA and AA were D60 and D61 in ICD-10 code. Study years for crude incidence/prevalence of AA/PRCA and trend of HSCT for AA/PRCA were from 2000 to 2005, and from 1997 to 2006, respectively. All patients were 10 or more years old. In terms of prevalence, PRCA was decreasing annually from 2000 to 2005 with 0.97, 1.12, 0.72, 0.61, 0.67, and 0.47 per 100,000 persons, respectively. On the contrary, the prevalence of AA was almost same from 2000 to 2005 with 11.28, 12.93, 12.36, 11.07, 11.09, and 10.54 per 100,000 persons, respectively. Female was more affected to both AA and PRCA. The average female to male ratios in AA and PRCA were 1.38 and 1.82. The peak decades of AA were fourth and fifth decades. On the other hand, the peak decades of PRCA were second and sixth decades. The frequency of HSCT for AA/PRCA was increasing in spite of the decreasing crude incidence during a decade from 1997 to 2006, in that 48, 56, 78, 88, 69, 68, 76, 85, 86, and 92, respectively. The frequency of HSCT was similar in both genders. In spite of the possibility of over-estimation, the prevalence of AA and PRCA was very higher in Korea than in western countries.

Patients with bone marrow failure syndrome (BMFS) are suffered from cytopenia and resulting requirement of transfusion. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the standard therapy for severe aplastic anemia (AA) with suitable sibling donor. However, it is true in many cases that alloHSCT can not be performed even in very severe AA due to no suitable donor. Although there were several reports of Alemtuzumab (ALM) for immune cytopenia and pure red cell aplasia, no report were published regarding ALM for BMFS. We studied the feasibility of ALM and cyclosporine A (CsA) for patients with BMFS. Inclusion criteria were transfusion-dependent BMFS including AA, myelodysplastic syndrome (MDS), pure red cell aplasia (PRCA). Prior IST or other drugs for BMFS except for ALM were not excluded. The dose of ALM was escalated from stage I dose (10mg on day 1, 20mg on day 2, and 30mg on day 3) to stage II dose (30mg/day for 3 days) along with CsA for at least 6 months. Prophylactic ciprofloxacin, acyclovir, and bactrim were given for first 2 months. Without partial response (PR) or more within 6 months, subsequent alloHSCT or antithymoglobulin therapy was allowed. Total 17 patients were enrolled. The majority was female (n=13, 76.5%). Median age was 48 (16–74) years. Diseases were 12 severe AA, 3 moderate AA and 1 hypoplastic MDS and 1 PRCA. All patients were transfusion-dependent. Fourteen patients were red cell transfusion-dependent and 12 patients were platelet transfusion-dependent. Median amount of transfused red cell, platelet concentrate and platelet apheresis prior to ALM-CsA were 6 (0–41), 3 (0–172) and 1 (0–22) units, respectively. Prior therapy were none in 13 (76.5%), anti-thymoglobulin in 3 (17.6%), and danazol in 1 (5.9%). Mean WBC, absolute neutrophil, hemoglobin and platelet were 3194 (600–6730)/mm3, 1365 (312–4257)/mm3, 7.3 (3.4–13.5)g/dl and 58K (3–334)K/mm3, respectively. Mean bone marrow cellularity was 11.9 (3–40)%. Patients received stage I dose in 13 and stage II dose in 4. Three patients could not receive full scheduled CsA because 2 patients died of infection and 1 patient underwent alloHSCT within 6 months after CsA. Median follow-up for response was 289 (91–691) days. Response to ALM-CsA were no response in 11 (64.7%), PR in 2 (11.8%), and CR in 4 (23.5%). Therefore, overall response rate was 6/17 (35.3%). Overall response in stage I dose and stage II dose were 5/13 (38.5%) and 1/4 (25%), respectively. All responsive patients showed their responses within 3 months. Median time to response was 55 (29–71) days. All CRs were converted from initial PR. Median time to CR and median time from PR to CR were 345.5 (91–691) and 278 (31–508) days. Neither diagnosis, fever nor skin rash during treatment did not affect the possibility of response to ALM-CsA (p=0.301, p=0.482, p=0.793, respectively). Toxicity during ALM was fever in 4 (23.5%), skin rash in 5 (29.4%), G1 ALT elevation in 7, G2 ALT elevation 2, G1 AST elevation in 5, and hyperbilirubinemia in 4 (G1 in 3, G3 in 1). There were no anaphylaxis, serum sickness or CMV reactivation. Three patients died of infection (n=2) or after alloHSCT (n=1). Four patients underwent alloHSCT after ALM-CsA treatment and 3 patients were successful.In spite of small number, ALM-CsA showed comparable response rate within 3 months after treatment. Therefore in conclusion, ALM-CsA is feasible and tolerable therapy for BMFS and stage I dose may be more recommendable.

Bortezomib has been used for patients with relapsed or refractory multiple myeloma. However, considering most patients with multiple myeloma are elderly people, the management of bortezomib-induced adverse effects became important. Varicella zoster virus (VZV) reactivation was reported as another adverse event associated with bortezomib in the APEX trial. Although some concomitantly administered drugs such as steroid may induce herpes zoster, proteasome inhibition itself may be associated with VZV reactivation because NF-κB inactivation may reduce antiviral response, and proteasome inhibition may affect the cellular localization of VZV leading to nuclear accumulation of VZV. Therefore, we analyzed the incidence of VZV reactivation among 267 relapsed or refractory myeloma patients treated with bortezomib. All patients were treated with at least one kind of treatment other than bortezomib before bortezomib therapy. 58 cases of VZV reactivation was observed (21.72%, 58/267) during or after bortezomib treatment while only 25 cases were found during other treatments such as VAD, MP etc (9.36%, 25/267). The incidence of VZV reactivation was not different based on the type of regimen: bortezomib monotherapy (22.58%) vs. bortezomib combined with dexamethasone, alkylating agents or thalidomide (22.72%). The characteristics of patients were compared in table. VZV reactivation (−) VZV reactivation (+) P value † number of prior VZV/total number of patients, ‡median (range), mean ± SD Age (median, range) 63 (43–82) 63 (37–82) n. s. Gender (male: female) 129:80 32:26 n. s. Number of prior zoster† 20/209 5/58 n. s. Disease duration (mean± SD) 3.57±3.01 years 2.33±1.99 years < 0.05 Number of prior treatment‡ 3 (1–7), 2.68±1.29 3 (1–7), 2.57±1.22 n. s. The incidence of VZV reactivation was not related with the disease (D-S stage, type), health status (performance status, co-morbidity, social history, blood cell counts), and other toxicity associated with bortezomib. The median time and mean cycles to the onset of VZV reactivation after the first infusion of bortezomib were 46 days (7–560 days), and 2.58±1.97 cycles. Localized herpes zoster was dominant form, and most cases showed a good response to anti-viral therapeutics without significant sequela. In conclusion, bortezomib was associated with high incidence of VZV reactivation. However, considering the absence of factors predicting VZV reactivation, further study should be warranted to determine the routine use of anti-viral prophylaxis.

Upfront high dose myeloablative chemotherapy followed by single ASCT is a standard therapy for the newly diagnosed MM patients under 65 years. Disease status after the induction chemotherapy is variable, so we evaluated the prognostic effect of the disease status at ASCT especially in the initial chemo-sensitive MM patients. We retrospectively analyzed the initial chemo-sensitive MM patients (≥ PR) enrolled from KMMWP web based registration (www.myeloma.or.kr). Between Nov 1996 and Jan 2007, 197 MM patients (median age 53) were treated with induction chemotherapy followed by single ASCT at 8 institutions in Korea. All the patients received PBSCs support after conditioning with melphalan alone. Some patients with no detectable M-protein without testing immunofixation or positive immunofixation result were classified as CR. Median follow-up time was 21.2 months (0.4–96.0) from the day of ASCT. CR and PR at ASCT were achieved in 63 (32%) and 134 (68%), respectively. The initial DS stage was not correlated with disease status at ASCT, but initial low stage according to the ISS & SWOG staging system were correlated with CR status at ASCT (P=0.017, P=0.044, respectively). Overall survival from the day of ASCT (OS) was significantly correlated with CR status at ASCT comparing with PR status at ASCT (P=0.0015). OS according to the status at ASCT among the patients who received VAD induction chemotherapy (N=161) showed same results (P=0.002). CR status after ASCT also predict OS (P=0.0135), but the MM patients with continued CR after ASCT showed significantly higher OS after ASCT compared with induced CR patients after ASCT who had PR status before ASCT (P=0.0178). Multivariate analysis indicated that status at ASCT (CR versus PR) was a significant prognostic factor for prediction of OS after ASCT (P=0.012 by Cox proportional hazard analysis, OR=2.83, 95% CI, 1.25–6.37). We concluded that MM patients with CR at ASCT had better OS comparing with PR at ASCT. And continued CR status after ASCT may be a very important prognostic factor. So we should try more intensive induction chemotherapy regimens including new anti-myeloma agents to achieve maximum response status just before ASCT. Figure. (A) OS according to status at ASCT, (B) OS according to status after ASCT. (C) OS according to status after ASCT only in the MM patients who achieved CR after ASCT (N = 147). Figure. (A) OS according to status at ASCT, (B) OS according to status after ASCT. (C) OS according to status after ASCT only in the MM patients who achieved CR after ASCT (N = 147).

It is well known that HSP is influenced by temperature. Here we searched the effects of temperatures on preservation of hematopoietic stem cells (HSC) and the changes of HSP according to the temperatures and cryopreserving agents. The G-CSF-mobilized peripheral blood HSCs were collected from a healthy donor. DMSO, EG and GLY were used for cryopreserving agents. HSP were measured by real-time quantitative PCR, and cell viability were measured by trypan blue stain and MTS assay, respectively. Testing temperatures were 4°C, room temperature (RT, 20°C) and 37°C. Samples were HSCs stored according to testing temperatures without cryopreserving agents (cycle 0), HSCs thawed after first cryopreservation with various cryopreserving agents (cycle 1). The measure was done daily from D0 to D5 at cycle 0, and in 30 minutes interval (0, 30, 60, 90, 120 min) at cycle 1. Whereas more than 98% of cells were viable till 5 days after the harvest of cycle 0 at 4°C, RT and 37°C showed rapid decrease of viable HSCs. By day 3, less than 10% cells were viable at 37°C. At cycle 1, cell viability was rapidly decreased in both DMSO and GLY after 120 min stay at all temperatures. In case of EG, the same patterns were found at RT and 37°C. However, cell viability remained relatively well at 4°C. The expression of HSP 27 were over-expressed by day 2 and suppressed thereafter at all temperatures of cycle 0. At 4°C of cycle 0, the over-expression of HSP 27 was greater than those at RT and 37°C. The expression of HSP 70 was mostly suppressed along times. The suppression at 37°C was greater than those of other temperatures. In case of HSP 90, the overall expression was suppressed except for day 2 at 4°C and RT. At all cases of cycle 0, the expressions at 37°C were lower than those at 4°C and RT. At 4°C of cycle 1, DMSO showed decreased expression of HSP27 and HSP70. In contrast to DMSO, the expression of HSP27 and HSP70 was increased in case of EG and GLY at 4°C of cycle 1. The over-expression of HSP90 at 4°C of cycle 1 in EG and GLY was very low compared with those in DMSO. Overall expressions of HSPs in GLY were lower than in DMSO or EG at RT of cycle 1 except for HSP27. The expression of HSP27, HSP70, HSP90 were all decreased at 37°C of cycle 1 except for HSP70 in EG and HSP90 in DMSO. In conclusion, we should keep cool when storing HSCs without cryopreserving agent. The rapid apoptosis at 37°C could be caused by changed expression of anti-apoptotic HSPs. The expression of HSPs influenced by temperatures and cryopreserving agents may affect the viability of HSCs through the changes of HSPs.

The effectiveness of anthracycline dose intensification for induction of CR in AML has not been studied in a randomized fashion. We conducted a prospective randomized trial to compare the therapeutic efficacy and toxicity of two different doses of daunorubicin in combination with cytarabine in AML. This study began on August 2001 and 293 adult patients (younger than 60 years) with newly diagnosed AML except M3 have been enrolled. Fourteen patients were removed from the study and the remaining 279 patients were analyzed. After random assignments, 135 patients received standard-dose daunorubicin (SD-DN, 45 mg/m2/d × 3 d) and 144 patients received high-dose daunorubicin (HD-DN, 90 mg/m2/d × 3 d) in addition to cytarabine (200 mg/m2/d × 7 d) for induction of CR. Patients with persistent leukemia received the second attempt of induction chemotherapy, consisting of standard-dose daunorubicin (2 d) plus cytarabine (5 d). Patients who attained CR received 4 cycles of high-dose cytarabine (3 g/m2 × 6 doses) and 2 cycles of daunorubicin (1 d) plus cytarabine (5 d). For patients in intermediate- or high-risk cytogenetic groups, allogeneic hematopoietic cell transplantation was performed if there was a suitable donor. CR was induced in 98 of 135 patients (72.6%) in SD-DN arm and 119 of 144 (82.6%) in HD-DN arm (P = 0.044). The impact of daunorubicin dose intensification on the CR rates were different by cytogenetic risk group: the CR rates for SD-DN vs. HD-DN arm were 24/25 (96.0%) vs. 35/36 (97.2%) for good-risk group, 63/88 (71.6%) vs. 64/83 (77.1%) for intermediate-risk group, and 10/20 (50.0%) vs. 19/24 (79.2%) for poor-risk group. With a median follow-up of 596 days for surviving patients, the 4-year probabilities of overall survival, disease-free survival, and relapse-free survival were similar between SD-DN and HD-DN arm. Two different doses of daunorubicin (SD-DN vs. HD-DN) showed similar toxicity profiles regarding recovery times from myelosuppression, transfusion requirements, severe toxicities (grades III to IV) classified by NCI-CTC ver 2.0 including cardiac toxicities, and duration of antibiotics administration. In conclusion, high-dose daunorubicin showed higher CR rates in AML patients of intermediate- and poor- cytogenetic risk groups without increase of toxicities compared to standard-dose daunorubicin.

Continuous infusion (CI) of cytarabine and fludarabine can accentuate drug activities. We studied the feasibility and the efficacy of fludarabine and cytarabin as a continuous infusion plus idarubicin for resistant AML under 60 years old. Inclusion criteria were AML except for acute promyelocytic leukemia, patients with resistant acute myeloid leukemia (failure to achieve CR after initial induction chemotherapy including standard dose cytarabine; early relapse, occurring after a first CR lasting less than 12 months; relapse after allogeneic HSCT; relapses more than 2 times). Induction chemotherapy consists of idarubicin 12 mg/m2 iv infusion over 30 min (day 1–3), fludarabine 30 mg/m2/d and cytarabine 1000 mg/m2/d (day 1–5) as a 24-hour CI. G-CSF was added on day 1–5. Three more cycles of induction chemotherapy except for idarubicin were followed for consolidation. All 29 patients were enrolled. Median age was 40 (18–57). Disease status were primary refractory in 8 (27.6%), early relapse in 19 (65.5%), multiple relapse in 1 (3.4%), and relapse after SCT in 1 (3.4%). Translocation (8;21) and variants (8, 27.6%), and 2 or 3 abnormalities (7, 24.1%) were most common chromosomal abnormalities. Two patients (6.9%) could not complete induction. Twenty three patients had the early evaluation on median day 15 (14–42); median PB blast 0 (0–9.7) % and median bone marrow blast 0 (0–64) %. Median days for hematological recoveries in CR patients were follows: ANC > 500/mm3 (29 days); ANC >1000/mm3 (32 days); platelet >20K/mm3 (31.5 days); platelet>100K/ mm3 (43 days). Response for induction were CR in 8 (27.6%), CRp in 2 (6.9%), and treatment failure in 19 (65.5%, aplasia in 14, indeterminate course in 3, resistant in 2). Median days required for CR was 45 (37–63) days. Consolidation stopped in 9/11: 7 patients underwent SCT; 1 patient died during consolidation; 1 patient stopped due to toxicity; 1 patient due to other cause. Seven patients are alive and two were lost to follow-up. Nineteen patients died of infection (14 patients), toxicity during consolidation (1 patient), relapse after SCT (3 patients) and persistent disease (2 patients). Autolous SCT performed in 2 and allogeneic SCT in 5. Median overall survival in all and CR patients were 2.47 (95% CI 0.83–4.10) and 11.38 (95% CI 1.32–21.44) months, respectively. Relapse occurred after autologous SCT in 2/2 and after allogeneic SCT in 2/5. CI infusion of FLAG plus idarubicin was effective for eradicating blasts with expense of high toxic death. Reduced doses are recommended for CI of FLAG plus idarubicin.

Acute leukemia (AL) is a disease of challenge in that many patients die not only from eventual relapse but also from infection during treatment. In this regard efforts for decreasing infectious mortality will help increasing survival. Our previous study revealed that leukocyte bacteriocidal functions in chemotherapy-treated cancer patients were decreased and were stimulated by a novel hexapeptide, WKYMVm. We evaluated the leukocyte bacteriocidal function in patients with AL and searched whether WKYMVm can enhance the bacteriocidal function in patients with AL. On induction chemotherapy, blood sampling was performed at diagnosis and repeated weekly from start day of chemotherapy until patient died or complete remission was achieved. Tests were done weekly until white blood cell (WBC) count reached up to 1000/mm3 and platelet counts were stable without transfusion after consolidation chemotherapy. Nineteen AL patients and 10 healthy controls were enrolled. Diseases were acute myeloid leukemia (17 patients) and acute lymphoblastic leukemia (2 patients). Median WBC, absolute blast count (ABC) and absolute neutrophil count (ANC) at diagnosis were 5280/mm3 (range 840–315100), 162.9/mm3 (range 0–286741) and 796.4/mm3 (range 126–7336), respectively. Mean values of bacreriocidal activity at diagnosis were increased by concentrations of WKYMVm (13.4 at 0 nM; 24.9 at 1 nM; 33.3 at 10 nM; 38.5 at 100 nM; p

MALT림프종은 질병의 진행이 느리고, 진단 당시 국소적인 병변이 대부분이며, 폐와 위장관을 동시에 침범하는 경우는 매우 드물다. 저자들은 흉부 단순촬영에서 고립성 폐결절이 발견된 73세 남자 환자에서 위, 폐, 골수를 침범한 파종성 MALT림프종 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다.

In this study, we investigated the effect of an agonistic mAb (DTA-1) against glucocorticoid-induced tumor necrosis factor receptor (GITR) in a murine model of systemic lupus erythematosus (SLE)-like chronic graft-versus-host disease (cGVHD). A single dose of DTA-1 inhibited the production of anti-DNA IgG1 autoantibody and the development of glomerulonephritis, typical symptoms of cGVHD. DTA-1-treated mice showed clinical and pathological signs of acute GVHD (aGVHD), such as lymphopenia, loss of body weight, increase of donor cell engraftment, and intestinal damage, indicating that DTA-1 shifted cGVHD towards aGVHD. The conversion of cGVHD to aGVHD occurred because DTA-1 prevented donor CD8+ T cells from being anergic. Functionally active donor CD8+ T cells produced high levels of IFN-γ and had an elevated CTL activity against host antigens. In in vitro MLR, anergic responder CD8+ T cells were generated and DTA-1 stimulated the activation of responder CD8+ T cells that were fated to be anergic. We further confirmed in vivo that donor CD8+ T cells, but not donor CD4+ T cells, are responsible for the DTA-1-mediated conversion of cGVHD to aGVHD in a CD4+CD25+ regulatory T cell-independent manner. These results indicate that donor CD8+ T-cell anergy is a restriction factor in the development of aGVHD and that GITR stimulation prevent CD8+ T-cell anergy by activating CD8+ T cells prone to anergy. In sum, our data suggest GITR as an important costimulatory molecule regulating cGVHD versus aGVHD and as a target for therapeutic intervention in a variety of related diseases.

Compared to younger patients with acute myeloid leukemia (AML), elderly patients are associated with poorer prognosis and only a few survive long-term. Although several randomized trials demonstrate that elderly patients benefit from full-dose application of cytarabine plus anthracyclines rather than less intensive chemotherapy for induction therapy, optimal post-remission therapy remains to be determined. We performed a prospective phase II multicenter trial of standard induction therapy (7+3 of cytarabine plus daunorubicin) followed by 2 cycles of attenuated consolidation therapy (5+1 of cytarabine plus daunorubicin) for elderly AML patients excluding M3. This study was designed to reduce fatal complications by intensive post-remission therapy, benefits of which have not been evidenced in elderly patients. Induction therapy consisted of cytarabine (200 mg/m2/d x 7) and daunorubicin (45 mg/m2/d x 3). If interim bone marrow examination, which was done at 14 days after the start of induction therapy, showed persistent leukemia, the second attempt of induction therapy was tried with the same doses of cytarabine for 5 days and daunorubicin for 2 days. The patients who attained complete remission (CR) by induction therapy received 2 cycles of attenuated dose consolidation therapy (cytarabine 200 mg/m2/d x 5 plus daunorubicin 45 mg/m2/d x 1). Forty-one patients, 25 males and 16 females, were enrolled into the study between Jan 2002 and Dec 2004. Median age was 66 years (range, 60–78 years). Thirty-seven patients received the planned dose of induction therapy and 4 did not complete it due to intolerance in 3 or tumor lysis syndrome in 1. CR was attained in 16 patients after a first attempt of induction therapy. A second attempt of induction therapy was administered to 16 patients, 8 of whom attained CR. Overall, 24 (58.5%; 95% CI, 43.5–73.6%) of 41 enrolled patients achieved CR at a median of 34 days (range, 21–86 days). In the 17 patients who did not achieve CR, the cause of treatment failure was resistant leukemia in 15, complications of aplasia in 1, and indeterminate in 1. Of 24 CR patients, 17 completed all 2 cycles of consolidation therapy, 3 received 1 cycle, and 4 did not receive consolidation therapy. During induction therapy, most common non-hematologic toxicities (≥ grade 3) were febrile neutropenia (83%) and metabolic abnormalities (44%). During consolidation therapy, non-hematologic toxicities (≥ grade 3) were infrequent except febrile neutropenia (45% for the first consolidation and 41% for the second consolidation). There were no fatal complications during consolidation therapy. After a median follow-up duration of 566 days (range, 63–1190 days) among surviving patients, 27 died and actuarial 3-year overall survival was 17.0%. No patient died in remission. Fifteen of 24 CR patients relapsed and actuarial 3-year disease-free survival was 22.5%. Our study suggests that attenuated consolidation does not compromise the outcomes of elderly AML patients, compared to the results from previous reports using more intensive consolidation therapy.

6513 Background: Although adults with AML containing CBF translocations [t(8;21) or inv(16)/t(16;16)] have a high complete response (CR) rate and improved overall survival (OS) compared to other AML patients (pts), not everyone does well. Methods: In order to better understand the spectrum of CBF-associated AML, we analyzed 373 pts with newly diagnosed CBF-related AML treated on SWOG, ECOG or MDA protocols. Results: Pts ranged in age from 16–83 (median 39) with a slight male predominance (56%). Overall, 53% of pts had inv(16) or t(16;16) while 47% had t(8;21); 58% had chromosomal abnormalities in addition to the CBF translocation. Pts with t(8;21) tended to be younger (p=0.03), have lower white counts (p

Early intracranial hemorrhage (EICH), which is defined by noticeable ICH within 10 days of diagnosis, is a life-threatening hemorrhagic complication in patients with acute leukemia. To ascertain risk factors associated with EICH, we retrospectively analyzed 792 newly-diagnosed acute leukemia patients treated between July 1988 and March 2003. Thirty-one patients (3.9 %) had analyzable EICH. Multivariate analysis showed that female gender (OR = 3.064, P < 0.001), acute promyelocytic leukemia (OR = 8.797, P = 0.003), leukocytosis (OR = 6.056, P = 0.004), and prolonged prothrombin time (OR = 10.026, P = 0.016) were factors significantly associated with occurrence of EICH. Risk scores (RS) were calculated by a product of odds ratio and each risk factor (RF) and taking their sum, generating an RS ranging 0 to 27.943. The cutoff of RS 9 was of statistical significance to predict probability of EICH. Receiver-operating characteristics curve shows the sensitivity and 1 - specificity relative to risk score (AUC = 0.917; S.E. = 0.021; 95% CI, 0.876–0.958; Figure 1). In this regards, RF for EICH was classified as major (prolonged prothrombin time) and minor (female gender, acute promyelocytic leukemia, leukocytosis). Risk model demonstrated that EICH was low probable when no major RF and less than two minor RFs were present. Risk model for ICH in acute leukemia classified acute leukemia patients into two risk groups; low probable EICH group (LPG) and probable EICH group (PG). When applied to our patients, PG was positively correlated with more incidence of FICH than LPG (n = 27/173 vs. 4/619, P < 0.001). Induction chemotherapy could be undertook more frequently in LPG than in PG (p = 0.002, Table 1). Kaplan-Meier curves show the probability of EICH-free survival relative to probability of EICH. ICH-free survival was significantly longer in LPG than in PG (p < 0.0001, Figure 2). Our findings suggest that our risk model may predict the occurrence of EICH in patients with acute leukemia. Table 1. The relationship of risk model and frequency of early intracranial hemorrhage (EICH) or performance of induction chemotherapy. Figure Figure Figure Figure Low probable EICH group, n (%) Probable EICH group, n (%) P EICH (−) 615 (77.7 %) 146 (18.4 %) < 0.001 EICH (+) 4 (0.5 %) 27 (3.4 %) Induction chemotherapy (+) 563 (71.1 %) 143 (18.1 %) 0.002 Induction chemotherapy (−) 56 (7.1 %) 30 (3.8 %)

Absolute lymphocyte count (ALC) ≥1000 cells/mm3 on day +23 was an independent predictor of prolonged survival in patients with T/NK-cell lymphoma after autologous peripheral blood stem cell transplantation (APBSCT). To understand the prognostic value of lymphocyte recovery, we performed a retrospective study analyzing the result of 59 patients with multiple myeloma (MM) patients who underwent APBSCT. All patients were in complete or partial response after APBSCT. A median age at APBSCT was 51. Peripheral blood stem cells were mobilized and collected after cytoxan and G-CSF. The conditioning regimen was melphalan 200. ALC recovery day was defined as a first day of 3 consecutive days when ALC has been recovered more than 1000/mm3. A median value was used for the analysis of each noncategorical variable. A median follow-up time after APBSCT was 33.8 months and median recovery days of ALC ≥1000 cells/mm3 was 23 days. Prognostic factors at the time of APBSCT for transplant OS and PFS included beta-2 microglobulin, serum albumin, recovery days of neutrophil ≥500/mm3, infused mononuclear cell dose, infused CD+34 cell dose and recovery days of ALC ≥1000 cells/mm3. Univariate analysis revealed that significant variables at APBSCT for overall survival (OS) were beta-2 microglobulin, day of neutrophil engraftment and recovery days of ALC. Positive predictors at APBSCT for progression-free survival (PFS) were beta-2 microglobulin, day of neutrophil engraftment, serum albumin, infused mononuclear cell count, infused CD +34 cell count and recovery days of ALC. ALC ≥1000 cells/μL on day +23 was an independent predictive prognostic factors for better PFS (P = 0.003; Relative risk (RR) = 3.710; 95% Confidence interval (CI), 1.576–8.736) and showed tendency for prolonged OS (P = 0.065; RR=2.411; 95% CI, 0.946–6.142) (Table 1).In conclusion, ALC ≥1000 cells/mm3 recovery on day +23 was a good predictor for better survival in MM after APBSCT. Table 1. Multivariate analysis for OS and PFS Variables OS PFS RR 95% CI P RR 95% CI P ANC, absolute neutrophil count; MNC, Mononuclear cell; ALC, absolute lymphocyte count β2 microglobulin ≤ 3 vs > 3 mg/l 3.497 1.32–9.25 0.012 2.215 0.962–5.101 0.062 Serum albumin ≤ 3.7 vs > 3.7 g/dl 0.337 0.139–0.816 0.016 ANC≥ 500/mm³ recovery days≤ 11 vs > 11 2.677 1.044–6.864 0.040 1.360 0.616–3.001 0.447 Infused MNC dose≤ 3.4 vs > 3.4 ×10^8/kg 1.351 0.552–3.310 0.510 Infused CD+34 dose≤ 6 vs > 6 ×10^6/kg 0.609 0.209–1.779 0.365 ALC≥ 1000/mm³ recovery days≤ 23 vs > 23 2.411 0.946–6.142 0.065 3.710 1.576–8.736 0.003

Staging systems for multiple myeloma (MM) include the Southwest Oncology Group (SWOG) staging system, the International Staging System (ISS), and the Durie-Salmon (DS) staging system. We evaluated whether staging at the time of diagnosis could predict survival in MM patients undergoing autologous peripheral blood stem cell transplantation (APBSCT) as first-line treatment. Between November 1996 and June 2005, 152 MM patients were treated with induction VAD (vincristine, adriamycin, dexamethasone) chemotherapy, followed by APBSCT at 6 institutions in Korea. Median follow-up times were 22.6 months (range, 5.4-101.9 months) from the day of diagnosis and 14.1 months (range, 0.4-96.1 months) from the day of APBSCT. Progression-free survival (PFS) from the day of diagnosis was predicted by the SWOG staging system (P = .0129) and ISS (P = .0299), but not by the DS staging system at diagnosis (P = .1074). In addition, overall survival (OS) from the day of diagnosis could be predicted by the SWOG staging system (P = .0207) and ISS (P = .0105), but not by the DS staging system (P = .2542). PFS from day of APBSCT was not predicted by the DS staging system (P = .5731), SWOG staging system (P = .2817), or ISS (P = .1167). OS from day of APBSCT could be predicted by the SWOG staging system (P = .0392) and ISS (P = .0198), but not by the DS staging system (P = .5426). Our findings indicate that PFS and OS in association with APBSCT can be predicted by stages assessed by the SWOG and ISS systems, but not by the DS system. Moreover, staging by the SWOG and ISS systems at the time of diagnosis was better correlated with survival than was staging at the time of APBSCT.

We retrospectively compared the outcomes of 225 patients with adult acquired aplastic anemia (AA) who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) from matched related donors (MRDs), and those treated by alloHSCT from alternative donors (ADs). Univariate and multivariate analyses of factors associated with survival were performed. Multivariate analysis showed that age at alloHSCT of ≤ 31 years, MRD, successful engraftment, absence of acute graft-versus-host disease (aGVHD), and platelet engraftment at ≤ 21 days, were independent predictors of longer survival. In addition, time to aGVHD and cumulative nonrelapse mortality (NRM) were better in MRD than in AD recipients. Using propensity score matching (PSM), we performed a case-control study comparing 25 patients in each group who underwent alloHSCT from MRDs and ADs. Pretransplantation clinical factors were well balanced in either group. Median survival time was similar, and no statistically significant difference in transplantation outcomes was apparent when MRD and AD recipients were compared. In conclusion, our results suggest that alloHSCT from an AD should be considered earlier in adult patients with AA who do not have an MRD.

Figure S1. Significant variants diagrams for UGT1A1 gene. Figure S2. Results of NaCl induced OFT. Table S1. Multi-gene panel for targeted sequencing. Table S2. List of protein simulation templates. Table S3. List of significant variants detected in RBC membrane protein-encoding genes. Table S4. Primer sets for all significant variants in RBC membrane protein-encoding genes. Table S5. List of significant variants detected in RBC enzyme-encoding genes among patients with HS. Table S6. List of UGT1A1 gene variants in patients with HS in Korea. Table S7. Clinical characteristics of patients with HS without peripheral blood spherocytes. Table S8. Patients without RBC membrane-encoding gene mutation. (DOCX 114 kb)

Figure S1. Significant variants diagrams for UGT1A1 gene. Figure S2. Results of NaCl induced OFT. Table S1. Multi-gene panel for targeted sequencing. Table S2. List of protein simulation templates. Table S3. List of significant variants detected in RBC membrane protein-encoding genes. Table S4. Primer sets for all significant variants in RBC membrane protein-encoding genes. Table S5. List of significant variants detected in RBC enzyme-encoding genes among patients with HS. Table S6. List of UGT1A1 gene variants in patients with HS in Korea. Table S7. Clinical characteristics of patients with HS without peripheral blood spherocytes. Table S8. Patients without RBC membrane-encoding gene mutation. (DOCX 114 kb)