Posaconazole at Standard Dose Is Safe and More Effective Than Echinocandins As IFD Prophylaxis in Patients with FLT3 Mutated AML Treated with Midostaurin

Abstract Introduction. The potential drug-drug interactions of midostaurin (M), particularly with CYP450 inhibitors, may impact the choice of antifungal (AF) prophylaxis and treatment in FLT3-positive (FLT3+) acute myeloid leukemia (AML) patients (pts). However, there are no supportive data to guide the choice of AF drugs in this subset of pts. Aim. To evaluate the incidence of invasive fungal diseases (IFD) during induction and consolidation treatment of FLT3+ AML pts and to correlate it to the different AF prophylaxis strategies adopted. Patients and Methods. Within the SEIFEM (Sorveglianza Epidemiologica Infezioni nelle Emopatie) Group, we planned a restrospective/prospective multicenter observational study enrolling all FLT3+ AML pts treated with chemotherapy (CHT)+M. IFD were classified as possible, probable and proven according to EORTC/MSG revised definitions (Donnelly JP et al, Clin Infect Dis 2020). Relationships between the type of AF prophylaxis, IFD development and AML outcome were evaluated. Results. As of 30 th June, 90 pts treated with CHT+M as induction/reinduction, consolidation or both, have been enrolled. M/F ratio was 35/55, median age 56y (range 18-78). FLT-ITD and FLT3-TKD mutations were detected in 73 and 17 pts, respectively, NPM-1 mutation in 51 (57%) pts. AML risk stratification according to ELN classification was available in 80 pts (24 low risk). A total of 216 CHT+M courses have been delivered (85 inductions, 8 reinductions and 135 consolidations). Overall, 25 IFD were reported: 19 during induction (22%), 2 during reinduction (25%) and 4 during consolidation (3%) given without AF prophylaxis in all the four. Sixty-five (72%) pts achieved complete remission (CR) after the induction. During induction, 11 pts did not receive mold-active AF prophylaxis and developed 4 (36%) IFD (3 possible and 1 probable aspergillosis), while 74 pts received mold-active AF prophylaxis and developed 15 (20%) IFD (8 possible and 4 probable aspergillosis, 3 candidemia). Incidence according to mold-active AF prophylaxis strategy was: 7/40 (17%) with posaconazole 300 mg/d, 5/13 (38%) with echinocandins (micafungin 50 mg/d or caspofungin 70>50 mg/d), 2/17 (12%) with posaconazole given for 7 days followed by micafungin or caspofungin, 1/2 with isavuconazole 200 mg/d, and 0/2 with L-AmB 50 mg every other day). A posaconazole-containing AF prophylaxis regimen was protective against IFD (9/57, 16%, vs 10/28, 36%, p=0.05), while a trend toward a higher incidence of IFD was observed in pts receiving echinocandins alone as AF prophylaxis (5/13, 38%, vs 14/72, 19%, p=0.15). IFD were more frequent in pts aged 60y or older (11/31, 35%, vs 8/54, 15%, p=0.034), while no correlations between IFD and gender, ELN classification, failure to achieve CR were observed. At multivariate analysis, age≥60y was confirmed as a risk factor for IFD (OR 3.021, CI 1.028-8.849), while receiving AF prophylaxis without posaconazole was of borderline significance (OR 2.817, CI 0.955-8.306). Three pts out of 40 on posaconazole prophylaxis received reduced dose of M (50 mg/d). M was discontinued in 12 pts during induction; of these, 6 (50%) did not achieve a CR. IFD was the main reason for M discontinuation in 6 pts; in the other 6, toxicity was responsible (QTc prolongation in 3, 1 during caspofungin, 1 during posaconazole and 1 out of AF prophylaxis; gastrointestinal toxicity in 2, 1 during posaconazole and 1 during caspofungin prophylaxis; liver toxicity in 1, during posaconazole prophylaxis). After a median follow-up of 5 months, overall survival (OS) was similar in pts with or without IFD (p=0.294), while in those not achieving CR after first induction it was significantly lower in pts developing IFD (p=0.03) (Fig. 1A and 1B). Conclusions. IFD is still a frequent complication during AML induction treatment, also in patients receiving AF prophylaxis; it is associated with a frequent discontinuation of M and to a worsening of OS in patients not in CR after the first induction, probably contributing to a delay in the appropriate timing of the AML treatment. A posaconazole-containing prophylaxis was a better strategy against IFD occurrence, compared to echinocandins alone. M discontinuation for toxicity was a relatively rare event and no specific relationship with the type of AF prophylaxis ongoing was observed. A study evaluating plasma M levels during different prophylaxis strategies adopted is ongoing within the SEIFEM group. Figure 1 Figure 1. Disclosures Fracchiolla: Gilead: Honoraria, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rossi: Alexion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Pagano: Gilead Sciences, MSD, Pfizer Pharmaceuticals, Astellas Pharma: Speakers Bureau; Gilead Science, MSD, Pfizer, Basilea, Janssen, Novartis, Jazz Pharmaceutical, Cidara: Membership on an entity's Board of Directors or advisory committees; Menarini: Consultancy.

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Management of Secondary Prevention in Venous Thromboembolism: Use of Reduced Doses of Rivaroxaban and Apixaban in Extended Therapy

Blood ◽

10.1182/blood-2020-141908 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 16-17

Author(s):

Desiree Campoy ◽

Katia Flores ◽

Gonzalo Artaza ◽

César A Velasquez ◽

Tania Canals ◽

...

Keyword(s):

Venous Thromboembolism ◽

Secondary Prevention ◽

Board Of Directors ◽

Dose Reduction ◽

Standard Dose ◽

Control Group ◽

Advisory Committees ◽

The Mean ◽

D Dimer

BACKGROUND After a standard anticoagulation period (3-6 months), the risk of venous thromboembolism recurrence (RVTER) needs to be considered. Such risk is higher in unprovoked events and patients with persistent risk factor. The increase of D-dimer (DD) levels during the therapy seems to be strongly associated to RVTER. The use of rivaroxaban 10 mg/day and apixaban 2.5mg/12h as an extended therapy (ET) after the standard anticoagulation period has been proven to be an effective strategy to prevent recurrence without increasing bleeding events. AIM To assess the effectiveness and safety of reduced doses of rivaroxaban and apixaban as ET in patients with RVTER and to compare their DD levels with those of a control group on anticoagulant therapy at a standard dose. METHODS From April 2016 to June 2020, we included patients with venous thromboembolism (VTE) who received ET with rivaroxaban and apixaban with/at reduced doses. Dose reduction was performed following the clinical algorithm of our unit (Fig. 1). The DD values were determined using HemosIl D-Dimer HS-500 and the cut-off value was established at 500 µg/L DD levels were compared with a control group of 235 patients with VTE who received ET with standard doses of anticoagulation. DD levels were measured at the time of diagnosis (D1), initiation of treatment (D2) and 3 months after treatment (D3). RESULTS From a total of 116 patients (65.5% women), 77.6% (n=90) received rivaroxaban 10 mg/24h and 22.4% received apixaban 2.5 mg/12h as an ET. The mean duration of the initial anticoagulant therapy was 12 +/- 8.8 months. The mean DD value prior to the ET was 388 µg/L. In this group, 63.8% (n=74) was an unprovoked VTE and 17.2% (20) had hereditary thrombophilia. The mean of follow-up time was 6.9 +/- 8.3 months. No recurrences of VTE were observed during the follow-up and only one major bleeding event was reported in a high-bleeding risk patient. We observed a progressive decrease of DD levels from the VTE diagnosis to the last visit, with D1, D2, and D3 values of 987 µg/L ± 324, 388 µg/L ± 134, and 288 µg/L ± 98, respectively. There were no differences in d-dimer concentrations between patients with reduce doses of rivaroxaban or apixaban and the control group with standard doses (D1: 85.6% vs 81%, p =0.22; D2: 10.2% vs 8.0%, p =0.14; and D3: 9.1% vs 9.5%, p =0.18). CONCLUSIONS Our data indicated that an ET strategy with reduced doses of rivaroxaban or apixaban is effective and safe. We did not observe significant differences in DD levels at follow-up compared to the control group receiving a standard dose of anticoagulation. Further studies are needed in order to select and standardize dose reduction criteria in secondary prevention. Figure 1 Disclosures Campoy: boehringer ingelheim: Consultancy; Daiichi Sankyo: Speakers Bureau. Sierra:Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Research Funding; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead-Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Olivera:Daiichi Sankyo: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Boehringer Ingelheim: Consultancy, Speakers Bureau; BAYER: Consultancy.

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Repetitive Low-Dose Radiation Therapies As an Alternative Option for Indolent Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood.v128.22.1784.1784 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1784-1784

Author(s):

Khalil Saleh ◽

Jean-Marie Michot ◽

Alina Danu ◽

Julien Lazarovici ◽

Nadine Khalifé-Saleh ◽

...

Keyword(s):

Radiation Therapy ◽

B Cell ◽

Board Of Directors ◽

Low Dose ◽

Progressive Disease ◽

Standard Dose ◽

Low Dose Radiation ◽

Advisory Committees ◽

Dose Radiation

Abstract Introduction:Low-dose radiation therapy (LD-RT) is a therapeutic option in indolent non Hodgkin B-cell lymphomas (iNHL), usually in the palliative setting. If most iNHL are highly sensitive to radiation therapy, with good local control obtained with a dose of 4 Gy in 2 fractions, little is known about the efficacy and outcome of repetitive courses of LD-RT. We report here the results of a study cohort of repetitive LD-RT in iNHL. Methods : We retrospectively reviewed the records of all iNHL patients treated by two or more courses of LD-RT at Gustave Roussy, between January 1990 and December 2015. Patients received LD-RT as palliative treatment for low-bulky disease, patient's comfort or painful adenopathy. Clinical data, histological types, outcome and treatment lines were collected. Overall survival was the time between lymphoma diagnosis and death from any cause. Last LD-RT follow-up period was the time between the last LD-RT session and latest news. Results: Thirty-five pts were analyzed. Among them, 24 pts (69%) had Follicular Lymphoma (FL), 6 pts (17%) Marginal Zone Lymphoma (MZL), 3 pts (9%) had B-cell primitive Cutaneous Lymphoma Follicular Type (CL-FL) and 2 pts (6%) Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL). At lymphoma diagnosis, median age was 57 years [range 20-80]. Ann Arbor stage was I-II in 18 pts (51%), and III-IV in 17 pts (49%). Patients received a median of 4 therapeutics lines (range 2-11), and 2 LD-RT courses (range 2-6). Median overall survival was 146 months [29-298 months]. Four patients had died: 2 of disease progression and 2 others from concomitant illness (1 cardiac disease and 1 hepatocellular carcinoma). No patient had experienced transformation to diffuse large B cell lymphoma after RT-LD treatments. In the vast majority of cases (31/35; 89%), the LD-RT were successively performed to lymphoma relapse outside irradiation fields. Exclusive repetitive courses of LD-RT without chemotherapy were received by 8/35 (23%) of patients; while 24/35 (69%) patients received repetitive LD-RT alternately with immunotherapies or chemotherapies; and 3/35 (9%) others repetitive LD-RT alternately with standard dose RT. After the second course of LD-RT, 12/35 (34%) patients were managed in watch and wait approach, 6/35 (17%) received another LD-RT and 17/35 (49%) patients had experienced a progressive disease and were treated with immunotherapy or chemotherapy or standard dose radiotherapy. The LD-RT was the last treatment modality in 18/35 (51%) patients with histological types distributed in FL (n=10), MZL (n=5) and CT-FL (n=3). With a median last LD-RT follow up of 32 months [7-177 months], 23/35 (66%) patients remained in complete remission, 9/35 patients (26%) had experienced progressive disease and 3/35 (9%) patients had obtained stable disease. Conclusion: As palliative treatment modality, the repetitive low dose radiation therapy 4 Gy in two fractions could provide alternative option treatment in iNHL. This study support further investigations of this simple, well tolerated and not costly therapy in iNHL, especially in the context of new immunotherapeutic agent's area. Disclosures Michot: Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Ribrag:ArgenX: Research Funding; Esai: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; NanoString: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees.

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Thalidomide Maintenance Significantly Improves Progression-Free Survival (PFS) and Overall Survival (OS) of Myeloma Patients When Effective Relapse Treatments Are Used: MRC Myeloma IX Results

Blood ◽

10.1182/blood.v116.21.623.623 ◽

2010 ◽

Vol 116 (21) ◽

pp. 623-623 ◽

Cited By ~ 11

Author(s):

Gareth J Morgan ◽

Faith E. Davies ◽

Walter M. Gregory ◽

Sue E. Bell ◽

Alex J. Szubert ◽

...

Keyword(s):

Mathematical Model ◽

Multiple Myeloma ◽

Maintenance Therapy ◽

Board Of Directors ◽

Induction Treatment ◽

Newly Diagnosed ◽

Advisory Committees ◽

Relapse Treatment ◽

Fish Group

Abstract Abstract 623 Background: Although a meta-analysis has suggested that a consistent PFS benefit is seen with maintenance thalidomide therapy in multiple myeloma (MM) patients, the impact on OS remains unclear (Hicks LK, et al. Cancer Treat Rev 2008;34:442-452). This could be due to a lack of effect, differing biological subgroups in relatively small studies with short follow-up, or lack of effective relapse treatment. Aims: The study was set up to evaluate the effect of thalidomide maintenance therapy in newly diagnosed MM patients aged ≥ 18 years with OS and PFS as end points, and to examine differential effects in fluorescence in situ hybridization (FISH) identified molecular subgroups. Methods: Following induction treatment in an intensive pathway for younger fitter patients and a non-intensive pathway for the remaining patients, eligible patients were randomized to open-label thalidomide maintenance until progression (50 mg/day escalating to 100 mg/day after 4 weeks assuming good tolerance) or no maintenance. Patients of all ages were included in the randomization. FISH was performed using standard approaches. Adverse FISH groups were defined as any of t(4;14), t(14;16), t(14;20), 1q+, 17p−, or 1p32− (in the intensive pathway only); the remainder were defined as favorable. Results: Overall, 820 patients were eligible of which 818 were evaluable. Median patient age was 65 years (range, 31−89). Median follow-up from maintenance was 38 months (range 12−66 months). Median time on maintenance was 7 months (range 0−50 months). Maintenance thalidomide significantly improved PFS, with a difference between the curves of 13% (95% confidence interval [CI] 6%−20%) established by 24 months and maintained till the current maximum follow-up at 66 months (hazard ration [HR] 1.36; 95% CI 1.15−1.61; logrank P < 0.001). However, in the initial analysis there was no apparent impact on OS (P = 0.40). These findings were consistent regardless of prior intensive or non-intensive induction treatment. At 66 months follow-up, a PFS benefit was seen in the favorable FISH group (P = 0.004) with no effect on OS (P = 0.6). In the adverse FISH group there was no effect on PFS (P = 0.48) and a negative effect on OS (P = 0.009). Subsequently, we evaluated the effect of relapse treatment on outcomes and used this data in a mathematical model to determine if OS benefit would have accrued from the prolonged PFS if all patients had received effective treatment at relapse. A total of 523 patients have progressed to date and of these, 47% received thalidomide as initial relapse treatment (either as a single agent or in combination), 30% received novel agents (either bortezomib or lenalidomide), and 27% received alkylating agents or steroids. Median survival after progression was significantly worse in patients who received thalidomide maintenance than those who did not (P < 0.005); this could, at least partly, be attributed to patients who received thalidomide at progression. In those patients, the median OS after progression was significantly greater in the no maintenance group versus the thalidomide maintenance group (P = 0.004). Among patients treated with novel agents at progression, prior thalidomide maintenance therapy had no impact on OS and these patients were effectively salvaged. The mathematical model employed to examine the effect of effective salvage therapy at progression suggested that a significant survival benefit of 5.5% at 3-years in favor of thalidomide maintenance would have accrued if all patients had received effective therapy at progression (HR 0.77; 95% CI 0.60–0.99; P = 0.04). Next, we examined whether continuous thalidomide therapy was associated with a consolidation or maintenance effect. Upgrading of response with thalidomide maintenance was not common. Importantly, there was no difference in response over time between maintenance therapy and no maintenance. In contrast to what has been reported previously, these findings suggest a maintenance effect. Conclusions: Maintenance thalidomide significantly improves PFS and if effective relapse treatment is available this translates into an OS advantage. The median duration of maintenance thalidomide therapy of 7 months in the present study was short. The clinical impact of maintenance would be improved if patients could remain on therapy for longer, suggesting that the use of other agents such as lenalidomide, with better tolerability profiles, may produce better results. Disclosures: Off Label Use: THALOMID (thalidomide) in combination with dexamethasone is indicated for the treatment of patients with newly diagnosed multiple myeloma. Davies:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ortho Biotech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees.

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Allogeneic Hematopoietic Stem Cell Transplantation in First Line High Risk Multiple Myeloma Patients: Evolving Strategies with the Immunomodulating Drugs.

Blood ◽

10.1182/blood.v120.21.3116.3116 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3116-3116

Author(s):

Mauricette Michallet ◽

Mohamad Sobh ◽

Jean El-Cheikh ◽

Stéphane Morisset ◽

Anne Sirvent ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Risk ◽

Board Of Directors ◽

Induction Treatment ◽

High Dose ◽

First Line ◽

Advisory Committees ◽

Β2 Microglobulin

Abstract Abstract 3116 We evaluated in this study the efficacy and toxicity of a pilot tandem auto-HSCT strategy followed by reduced intensity conditioning (RIC) and allogeneic HSCT with the post-allo-HSCT introduction of bortezomib and donor lymphocyte infusion (DLI) in high risk multiple myeloma (MM) patients (Group1). We compared our results to those observed after traditional tandem auto-RIC-allo-HSCT without bortezomib after allo-HSCT (Group2). Groups 1 and 2 were compared to matched patients not receiving allo-HSCT from the IFM previous prospective studies. Matching variables were: diagnosis date, age, gender, β2 microglobulin, cytogenetics and induction treatment, the matching ratio was 1:3. Groups 1 & 2 included MM patients of age ≤ 65 years who previously received vincristine, doxorubicin and high-dose dexamethasone (VAD) or bortezomib plus dexamethasone (VD) as induction treatment followed by auto-HSCT. Only patients who achieved at least a partial response (PR) after auto-HSCT were included. Patients must have an HLA identical related or unrelated donor, and at least one of the following factors: β2 microglobulin level >3mg/L, del13, t(4;14) or del17p. The conditioning regimen combined fludarabine 30 mg/m2/d (d-5→d-1), busilvex IV 3.2 mg/kg/d (d-4, d-3) and ATG 2.5 mg/kg/d (d-2, d-1). GVHD prophylaxis consisted on cyclosporine A 3mg/Kg from day -1 with the addition of methotrexate at days 1, 3 and 6 in case of ABO incompatibility. In group1, by day 90 post-allo-HSCT, patients not in CR received 4 cycles of bortezomib 1.3 mg/kg (21 days cycle, on days 1, 4, 8 and 11); if the CR was not achieved, increasing doses of DLI were administered. Allo-HSCT groups included 25 patients (12 in group1 and 13 in group2), 18 males and 7 females with a median age of 51 years [28–67], there were 15 IgG, 6 IgA and 4 light chains MM. Fourteen (56%) patients had del13, 7 (28%) del17 and 17 (68%) had β2 microglobulin level >3mg/L. Induction treatment was VAD in 16 (64%) patients and VD in 9 (36%). Twenty-one (84%) patients received high dose melphalan (200 mg/m2) while the rest received a dose of 140 mg/m2; auto-HSCT was performed after a median time of 5.5 months [3.6–15.3] from diagnosis. The median time between auto-HSCT and allo-HSCT was 3.8 months [2.5–8.5]. The stem cell source was peripheral HSC in 22 (88%) of cases and the median number of infused CD34+ cells was 6.1×106cells/Kg (range: 2–13) from 16 identical siblings and 9 HLA (10/10) matched unrelated donors. Sex matching was as follow: F→M:9, F→F:3, M→F: 4 and M→M:9 and for ABO compatibility, 18 (72%) were compatible, 1 had minor incompatibility and 6 major incompatibility. At allo-HSCT, one patient was in CR, 4 in very good partial response (VGPR) and 20 patients were in PR. The matched population included 36 controls for group1 and 39 for group2. At Day 90 after allo-HSCT, all patients engrafted, 10 patients were in CR and 15 patients were in less than CR. Nine patients in group1 received bortezomib, 3 reached a CR while the 6 others were still in PR and received increasing doses of DLI. There were 8 acute GVHD [7 grade II (3 in group1) and 1 grade III in group1] and 11 chronic GVHD [3 lim. (all in group1) and 8 ext. (1 in group 1)]. No GVHD reactivation was observed after DLI. At the last follow-up, 14 patients are alive (9 in group1 and 5 in group2), 10 patients were in durable CR1 post-allo-HSCT and 4 patients in PR after DLI; 11 patients died (3 in group1: all from progression; 8 in group2: 5 from progression and 3 from TRM). After a median follow-up of 55 months [3–142], the median OS was not reached in group1 vs. 65 months (51-NR) in its matched patients (p=0.027); and it was 96 months (49-NR) in group2 vs. 91 months (32-NR) in its matched patients (p=0.77). The median PFS was 49 months (29-NA) in group1 vs. 25 months (21–35) in its matched patients (p=0.0045); and it was 31 months (22-NR) in group2 vs. 28 months (21–40) in its matched patients (p=0.0776). The encouraging results observed in group1, in terms of OS, PFS and toxicity are due to the introduction of IV busilvex and better ATG administration schedule in addition to the immunomodulating role of bortezomib in the elimination of the residual disease. In addition, we showed a good GVL effect after DLI with a durable stability of the disease without any important GVHD complication. According to our promising results, we should reconsider the allo-HSCT in the context of first line treatment for high risk MM patients. Disclosures: Nicolini: Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Attal:celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees.

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Is Stem Cell Transplantation for Transformed Follicular Lymphoma Required in the Rituximab Era?: The Royal Marsden Experience 2003-2013

Blood ◽

10.1182/blood.v124.21.1719.1719 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1719-1719 ◽

Cited By ~ 1

Author(s):

Mary Gleeson ◽

Eliza A Hawkes ◽

Clare Peckitt ◽

Andrew Wotherspoon ◽

Ayoma Attygalle ◽

...

Keyword(s):

Stem Cell ◽

Follicular Lymphoma ◽

Board Of Directors ◽

Research Funding ◽

Poor Prognosis ◽

Induction Treatment ◽

First Line ◽

Advisory Committees ◽

Transformed Follicular Lymphoma

Abstract Background: High-grade transformation (HT) of follicular lymphoma (FL) to diffuse large B-cell lymphoma (DLBCL) occurs at a rate of 3% per year and has been associated with a very poor prognosis, with a median overall survival (OS) of 1 year reported by Montoto et al in the pre-rituximab era. Treatment often includes upfront autologous or allogeneic stem cell transplantation (SCT) due to the poor prognosis, but rarely maintenance rituximab despite evidence in FL. These patients are excluded from the majority of clinical trials and hence the role of SCT in the rituximab era and maintenance rituximab are not well evaluated. Methods: We performed a retrospective analysis of all patients aged ≥18 years with histologically proven transformed follicular lymphoma (TFL) diagnosed and treated (≥1 cycle of chemotherapy) at our institute in the 10-year period 2003-2013. Histopathology databases were searched to identify patients diagnosed with DLBCL and FL (grade 1-3a). Clinical data were collated from electronic patient records. Patients with grade 3b FL were excluded. A minimum interval of 6 months between the diagnosis of FL and development of HT was required for inclusion to outrule a discordant lymphoma. All histological specimens were reviewed by an expert haematopathologist. The study was approved by our institutional review board. Results: Between March 2003 and May 2013, a total of 56 patients were diagnosed with TFL (to DLBCL) and received first-line induction treatment +/- autologous/allogeneic SCT. The median follow-up was 5.6 years. The median time from diagnosis of FL to HT was 5.3 (range 0.6-29.3) years with a median age at diagnosis of TFL of 61 years (range 34-85). 59% (n=33) had received prior chemotherapy for FL. At diagnosis of TFL 89% (n=50/56) of patients received chemotherapy +/- radiotherapy (IFRT) without subsequent SCT. Upfront autologous or allogeneic SCT post induction was performed for 4 (7%) and 2 (3.5%) patients respectively. 91% of patients (n=51/56) received rituximab containing (R) chemotherapy and 68% (n=38/56) were treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). 16.1% (9/56) received IFRT post induction. 14.3% (8/56) patients received R-maintenance following first-line treatment for TFL. For patients treated with R-chemotherapy alone (n=46) the 2 and 5-year OS and PFS (for TFL) were 84.5% and 70.9% and 58.7% and 49.3% respectively. In patients aged >65 years (n=17) 5-year OS was similarly 71.6%. Patients treated with R-CHOP had 2 and 5-year OS of 89% and 76% and PFS (TFL) rates of 59.5% and 51.7% respectively. Patients who received R-chemotherapy induction followed by R-maintenance (n=8) had both 2-year OS and PFS (TFL) of 100%. 82% of all patients (46/56) underwent FDG-PET on completion of induction treatment +/- SCT. A negative PET (n=30) was associated with 2 and 5-year OS rates of 90% and 74.1% and PFS (TFL) of 60% and 49.2%. Conclusion: The outcome for TFL has significantly improved with the advent of rituximab. In our analysis the 2 and 5-year OS rates of 84.5% and 70.9% with R-chemotherapy alone are superior to reported OS for patients undergoing upfront autologous/allogeneic SCT, while PFS rates are comparable to those quoted for upfront autologous SCT. Although the numbers are small (n=8) and follow-up shorter, the outcomes for patients treated with R-chemotherapy followed by R-maintenance (2-yr OS and PFS of 100% and 100%) are particularly encouraging while offering minimal additional toxicity. In conclusion our data indicate that upfront SCT may no longer be required for TFL in the rituximab era. Rituximab maintenance should be considered in the management of these patients. Disclosures Hawkes: Roche: Travel grant Other. Peckitt:Sanofi: Membership on an entity's Board of Directors or advisory committees. Dearden:Roche: Membership on an entity's Board of Directors or advisory committees. Cunningham:Astra Zeneca: Research Funding; Novartis: Research Funding; Merck Serono: Research Funding; Sanofi: Research Funding; Celgene: Research Funding; Amgen: Research Funding; Roche: Research Funding.

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Standard Dose Rituximab Plus 2–4 Cycles of Pulse Dexamethasone Is Effective and Tolerable in Treatment of Immune Thrombocytopenia (ITP)

Blood ◽

10.1182/blood.v118.21.1166.1166 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1166-1166

Author(s):

Rebecca Elstrom ◽

Waleed Ghanima ◽

Soo Y Lee ◽

Ithamar Turenne ◽

James B Bussel

Keyword(s):

Platelet Count ◽

Board Of Directors ◽

Research Funding ◽

Standard Dose ◽

Fisher Exact Test ◽

Sustained Remission ◽

Advisory Committees ◽

Pulse Dexamethasone ◽

Equity Ownership

Abstract Abstract 1166 Background: 70–80% of patients with ITP respond to initial corticosteroid-based treatment, but almost all experience recurrent thrombocytopenia requiring further therapy. Rituximab is effective in inducing responses in about 50% of patients with ITP, but most do not experience sustained remission. Strategies to improve the efficacy of rituximab would be of value. Cheng and colleagues have shown that a single 4 day course of dexamethasone is effective in newly diagnosed ITP, and GIMEMA demonstrated that multiple courses are even more efficacious. Zaja and colleagues reported that the combination of rituximab with a single course of dexamethasone is superior to dexamethasone alone in previously untreated patients. Given the activity of these two drugs, patients at Weill Cornell Medical College (WCMC) with ITP have been treated with a combination of standard rituximab and 2–4 cycles of pulse dexamethasone (R+Dex) given at 2 week intervals. We preliminarily reported results of 14 patients treated with this combination; we have expanded this cohort to 34 patients to obtain a broader evaluation of efficacy and safety of this therapeutic approach in ITP. Methods: Patients who had received rituximab concurrently with multiple courses of pulse dexamethasone were retrospectively identified. Response was initially assessed at 8 weeks after initiation of therapy. Complete remission (CR) was defined as platelet count greater than or equal to 100×109/L, and partial remission (PR) as platelet count of 50–100×109/L. Variables were compared either by chi-square or fisher exact test including duration of ITP at greater or less than one year, age of patients, prior therapy, and lymphocyte subsets. The study was approved by the WCMC Institutional Review Board. Results: Thirty-four ITP patients received concurrent rituximab and pulse dexamethasone. All patients were treated for platelet count less than 30 or inability to discontinue chronic therapy such as corticosteroids or thrombopoietin receptor agonist. Median age was 21 years (range 2–63 years), and median time since diagnosis of ITP was 12 months (range 1–180 months). All patients but one had previously been treated, with median of 2 prior therapies (range 0–7). Thirty-two of 34 patients received 4 infusions of standard dose rituximab (the other 2 received 2 and 3 infusions). All patients received between one and 4 cycles of dexamethasone, with most (22/34) receiving 3 cycles. Twenty-four patients responded at 8 weeks from start of therapy or later (71% ORR). Best response was CR in 20 patients (59%) and PR in 4 (12%). Two responding patients relapsed to no response at 3 and 6 months, and 3 additional patients relapsed from CR but maintained PR at last follow up. At median follow up of 8 months, 22 patients (65%) remain in response: CR in 47% and PR in 18%. None of the variables tested was predictive of response; there was a trend toward increased response rate in adults (p=0.13). Adverse events related to R+Dex were mostly mild, with most common toxicities including fatigue, headache, infusion-related events, and gastrointestinal upset. Dexamethasone was often poorly tolerated. One patient experienced colitis requiring hospitalization. That patient and one other interrupted therapy for AE's. Conclusion: Rituximab plus multiple courses of dexamethasone is active with manageable toxicity in patients with ITP. This regimen merits further exploration in a prospective trial. Disclosures: Elstrom: Genentech: Speakers Bureau. Off Label Use: Rituximab is approved for use in NHL, CLL and RA. Bussel:Portola: Consultancy; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cangene: Research Funding; Genzyme: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sysmex: Research Funding.

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Children Diagnosed with Acute Leukemia of Ambiguous Lineage (ALAL) Benefit from Acute Myeloid Leukemia (AML) Treatment Protocols: A Retrospective Analysis from a Single Center

Blood ◽

10.1182/blood-2020-142400 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 32-32

Author(s):

Georgia Avgerinou ◽

Ilona Binenbaum ◽

Stavros Glentis ◽

Marianna Tzannoudaki ◽

Stefanos Papadhimitriou ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Complete Remission ◽

Board Of Directors ◽

Myeloid Leukemia ◽

Induction Treatment ◽

Newly Diagnosed ◽

Advisory Committees ◽

Treatment Protocols ◽

Acute Myeloid

Background:Acute Leukemia of Ambiguous Lineage (ALAL) is a very rare type of leukemia, comprising 2%-5% of Acute Leukemias (AL). There is a lack of a uniform definition, with two different classification systems used (EGIL and WHO 2008/2016), making the optimal chemotherapy approach undetermined. Patients and Methods:The medical records of newly diagnosed ALAL patients (BAL based on the EGIL criteria or ALAL based on the 2008/2016 WHO criteria), who were admitted to our hospital from January 2012 to August 2020, were retrospectively reviewed. Patients characteristics including age, sex, blood count, blasts in bone marrow and peripheral blood, morphology, immunophenotyping, and cytogenetic/molecular studies were obtained. Treatment methods and outcome data including induction chemotherapy, complete remission (CR), relapse, use of Hematopoietic Stem Cell Transplantation (HSCT) in first CR (CR1), and death were reviewed. Results:Among a total of 168 newly diagnosed patients with AL, 7 (4.17%) patients (5 male & 2 female), fulfilled prerequisites of ALAL/MPAL. The median age at diagnosis was 5 years (range 1-14 years). Distinct dimorphic lymphoid and myeloid (monocytic) blast populations were present in one case with bilineal leukemia, as well as in two cases of biphenotypic leukemia. The remaining cases had morphologic and cytochemical features of Acute Myeloid Leukemia (AML), French-American-British (FAB): M1, M5 subtypes in two cases and Acute Lymphoblastic Leukemia (ALL) FAB L1-L2 subtype in one case. One case presented with early switch of lineage from ALL at diagnosis to AML M5 at the end of induction treatment. The AML directed regimen was associated with better complete remission rate at the end of induction treatment (CR 100%) compared to the ALL directed regimen (CR 0%). It is of note that the two patients that failed to achieve CR with ALL directed chemotherapy did respond to the AML induction treatment. Six patients underwent HSCT in CR1. One patient relapsed and underwent HSCT in CR2, but succumbed due to treatment related mortality during the transplantation period. At a median follow-up of 3.7 years (range 1-8 years) the 5-year overall survival (OS) and the event free survival (EFS) were 80% and 60%, respectively. Conclusions:Considering that ALAL is a very rare leukemia, the optimal treatment approach remains a dilemma for many clinicians. Although patient numbers are small and follow-up periods are short, the use of AML treatment protocols for ALAL appears to be promising and efforts need to be made on an international collaborative scale. Disclosures Kattamis: Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Vertex:Membership on an entity's Board of Directors or advisory committees;Genesis Pharma SA:Membership on an entity's Board of Directors or advisory committees;Apopharma/Chiesi:Honoraria, Speakers Bureau;Celgene/BMS:Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Ionis:Membership on an entity's Board of Directors or advisory committees;Agios:Consultancy;Vifor:Membership on an entity's Board of Directors or advisory committees.

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Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels

Blood ◽

10.1182/blood-2020-139431 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 48-49

Author(s):

Samantha Ferrari ◽

Chiara Pagani ◽

Mariella D'Adda ◽

Nicola Bianchetti ◽

Annamaria Pelizzari ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

High Risk ◽

Board Of Directors ◽

Advisory Board ◽

Advisory Committees ◽

Risk Status ◽

History Of ◽

Wbc Count

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P=<0.0001) predicted for arterial thromboses, while only a history of prior thrombosis (P=0.03) predicted for venous ones. In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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Evolving Unmet Need in Patients Refractory to Lenalidomide: Overview of the Clinical Trials in Relapsed/Refractory Multiple Myeloma

Blood ◽

10.1182/blood-2020-142642 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 22-23

Author(s):

Maria-Victoria Mateos ◽

Rohan Medhekar ◽

Istvan Majer ◽

Mehmet Turgut

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Literature Review ◽

Board Of Directors ◽

Unmet Need ◽

Publicly Traded ◽

First Line ◽

Advisory Committees ◽

Line Of Therapy

Introduction: The majority of newly diagnosed multiple myeloma (NDMM) patients are currently treated with lenalidomide-based regimens as their first line of therapy. This trend is likely to continue in the coming years. Typically, lenalidomide is administered until disease progression and has significantly contributed to better outcomes in these patients. However, most patients relapse, and prognosis worsens with each relapse. The choice of optimal treatment for patients who relapse while receiving lenalidomide as first line of therapy is unclear. Moreau et al (Blood Cancer J. 9, 38 [2019]) concluded that there is limited data on approved combinations for treating these patients and are restricted by the low number of lenalidomide-refractory patients enrolled in the pivotal trials. Results from the ongoing clinical trials of the combination of carfilzomib and anti-CD38 antibodies were not available at the time of the Moreau et al publication. The aim of this targeted literature review was to include this new data and to summarize currently available evidence on progression-free survival (PFS) for the treatment of RRMM patients who progressed on lenalidomide-based regimens. Methods: A targeted literature review was conducted to identify registrational clinical trials in patients with RRMM reporting PFS outcomes. PubMed, congress proceedings, and product labels were searched between Jan 2014 to July 2020. In addition to PFS, demographic, disease characteristics and treatment history were extracted for the trial populations to contextualize potential variations in study outcomes. The regimens studied in these trials were classified as lenalidomide-based, proteasome inhibitor (PI)-based and pomalidomide-based. Number of prior lines of therapy, prior exposure and refractoriness to lenalidomide and bortezomib were reported. Results: Twelve registrational trials were identified based on the search criteria (Table 1). Most pivotal trials assessing lenalidomide-based regimens (POLLUX, ELOQUENT-II, TOURMALINE-MM1) except the ASPIRE trial excluded patients who were refractory to lenalidomide. Trials evaluating PI-based regimens (e.g., CANDOR) or pomalidomide-based regimens (e.g., OPTIMISMM) included these patients, with more recent studies enrolling a larger proportion. Percentage of lenalidomide-exposed (and lenalidomide refractory) ranged from 40% (32%) in CANDOR to 98% (90%) in ELOQUENT III. These studies also enrolled a larger proportion of patients who were bortezomib-exposed, although most of these patients were at first relapse, with the exception of ELOQUENT III and ICARIA where most patients were at third relapse. Among lenalidomide-refractory patients, the median-PFS (mPFS) observed for the pomalidomide-based regimens ranged from 9.5 to 10.1 months and that observed for PI-based regimens ranged from 4.9 to 25.7 months. PFS in the lenalidomide-refractory subgroup was considerably shorter than in the ITT population. The mPFS for patients receiving carfilzomib/daratumumab/dexamethasone (KDd; CANDOR) and isatuximab/carfilzomib/dexamethasone (IsaKd; IKEMA) was not reached at median follow-up of 16.9 and 20.7 months respectively. While the mPFS for (KDd) for lenalidomide-refractory patients in CANDOR trial was not yet reached at median follow up of 16.9 months; the mPFS of 25.7 months for KDd in the MMY-1001 trial appears to be the longest among the assessed regimens. Conclusion: Patients refractory to lenalidomide have shorter PFS and represent a population with high unmet need. This targeted literature review suggests that the PI-based KDd regimen provides longer PFS compared to other lenalidomide-sparing regimens in lenalidomide-refractory populations. Heterogeneity across trial populations may limit the comparability of these treatments. Disclosures Mateos: Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaMar-Zeltia: Consultancy; GlaxoSmithKline: Consultancy. Medhekar:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Majer:Amgen (Europe) GmbH: Current Employment, Current equity holder in publicly-traded company.

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Comparable Outcomes between Unrelated Donor (8/8 or 7/8 matched) and Haploidentical Donor for Allogeneic Stem Cell Transplantation in Adult Patients with Severe Aplastic Anemia

Blood ◽

10.1182/blood-2019-130419 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4619-4619

Author(s):

Jee Yon Shin ◽

Sung-Soo Park ◽

Gi June Min ◽

Silvia Park ◽

Sung-Eun Lee ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Advisory Committees ◽

Sibling Donor ◽

Alternative Donor ◽

Matched Sibling ◽

Grade Ii

Background Either allogeneic hematopoietic stem cell transplantation (SCT) from HLA-matched sibling donor or immunosuppressive therapy (IST) has been recommended as one of the standard treatments for severe aplastic anemia (SAA). Regarding only 30% of chance finding HLA‐matched sibling donor, SCT from an alternative donor including unrelated (URD) or haplo-identical related donor (HAPLO) is considered to be a treatment option after failure to IST in patients who lack of a HLA-matched sibling donor. The aim of this study was to compare the outcomes of URD SCT and HAPLO SCT for SAA patients. Method Consecutive 152 adult patients with SAA who received first SCT between March 2002 and May 2018 were included: 73 of HLA-well-matched (8/8) URD (WM-URD), 34 of HLA-mismatched URD (MM-URD), and 45 of HAPLO. With the intention to have a follow-up period at least 1 year, data were analyzed at May 2019. A conditioning regimen with total body irradiation (TBI) and cyclophosphamide was used for URD-SCT, whereas that with TBI and fludarabine was administered for HAPLO-SCT (Lee et al, BBMT 2011;17:101, Park et al, BBMT 2017;23:1498, Lee et al, Am J Hematol 2018;93:1368). The combination of tacrolimus and methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. Results The median follow-up was 53.4 (range, 0.2-174.1) months. The median age of URD and HAPLO cohort was 30 (range 18-59) and 34 (range 18-59) years, respectively. Except for one and three patients who failed respective a neutrophil and platelet engraftment, other patients achieved neutrophil and platelet engraftments with median 11 and 15 days for WM-URD, 13 and 16.5 days for MM-URD, and 12 and 14 days for HAPLO, respectively. The five-years overall survival (OS), failure-free survival (FFS), and cumulative incidences (CIs) of graft-failure and transplant-related mortality were similar among three groups: 88.3%, 85.5%, 2.7%, and 11.7% for WM-URD; 81.7%, 81.7%, 0%, and 18.3% for MM-URD, and 86.3%, 84.1%, 6.7%, and 9.2% for HAPLO. The 180-days CI of grade II-IV acute GVHD in WM-URD, MM-URD and HAPLO were 35.6%, 52.9%, and 28.9%, respectively; and moderate to severe chronic GVHD were 28.7%, 38.7% and 11.8% in respective cohort. The CI of grade II-IV acute GVHD and moderate to severe chronic GVHD were significantly higher in MM-URD than those in HAPLO (both, p=0.026). ATG is the only factor affecting both grade II-IV acute GVHD (Hazard ratio 0.511, p=0.01) and moderate to severe chronic GVHD (Hazard ratio 0.378, p=0.003) in multivariate analysis. Other complications including CMV DNAemia, hemorrhagic cystitis, invasive fungal disease, secondary malignancy, and sinusoidal obstruction syndrome were similar among three groups. Survival outcomes of a subgroup of ≥ 2 allele MM-URD (n=16) extracted form MM-URD were inferior that of other donor types (n=136): 75.0% vs. 86.9% (p=0.163) for 5-year OS and 75.0% vs. 84.7% (p=0.272) for 5-year FFS. Conclusion This study shows that there were no significant differences between alternative donor sources in the absence of suitable matched sibling donor. Host/donor features and urgency of transplant should drive physician towards the best choice among alternative donor sources for SAA patients treated with SCT. However, selection of ≥ 2 allele MM-URD should not be recommended due to high incidence of GVHD and inferior outcomes. Figure Disclosures Kim: Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Amgen: Honoraria; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Honoraria; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; Otsuka: Honoraria. Lee:Alexion: Consultancy, Honoraria, Research Funding; Achillion: Research Funding.

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