Plt Recovery Research Articles

Efficacy of Hetrombopag in Treatment of Cancer Therapy-Induced Thrombocytopenia in Lymphoma and Multiple Myeloma Patients

Background: Chemotherapy and its combination are the mainstay of lymphoma and multiple myeloma (MM) treatment, with high-intensity regimens frequently causing cancer therapy-induced thrombocytopenia（CTIT）, which results in dose reductions and treatment delays. Hetrombopag, a novel oral non-peptide thrombopoietin receptor agonist, is approved in China for immune thrombocytopenic purpura and severe aplastic anemia. This study retrospectively evaluated the efficacy of hetrombopag in treating CTIT among lymphoma and MM patients. Methods: In this retrospective study, lymphoma and MM patients experiencing≥grade 2 thrombocytopenia (PLT<75×10 9/L) after anti-tumor treatment at the Fifth Medical Center of PLA General Hospital from July 2021 to May 2022 who received hetrombopag were included. All patients were treated with 5 mg hetrombopag once daily until PLT≥100×10 9/L or treatment discontinuation as directed by physicians. Results: A total of 60 patients (4 Hodgkin's lymphoma, 40 non-Hodgkin's lymphoma, and 16 MM) were analyzed. Their baseline characteristics are presented in Table 1. The median age was 58.0 years (range 14, 86), with 51 (85%) stage Ⅲ/Ⅳdiseases. Most patients received chemotherapy alone (40.0%, 24/60) or combined with targeted therapy (48.3%, 29/60). Notably, 90% patients received a combination of ≥3 chemotherapy drugs. The mean PLT before hetrombopag treatment was (38.8±15.6) ×10 9/L, with 81.7% (49/60) of grade 3/4 thrombocytopenia (PLT＜50×10 9/L). The median treatment duration with hetrombopag was 8 days (range 2, 28). The median time for PLT recovery to 75×10 9/L, and 100×10 9/L from hetrombopag initiation was 7 days (range 3, 14), and 9 days (range 3, 13), respectively. The mean PLT counts on days 3, 5, and 10 of hetrombopag treatment showed notable increases to (40.9±30.9) ×10 9/L, (54.9±37.8) ×10 9/L, and (94.4±70.5) ×10 9/L, respectively. Only 3 patients (5%) developed bleeding events, and 50% of patients avoided platelet transfusion. No hetrombopag-related adverse events were observed. Conclusion: With the limit of a retrospective evaluation, we observed that hetrombopag might increase PLT, shorten the duration of thrombocytopenia, with no significant toxicity, for lymphoma and MM patients who developed CTIT of ≥grade 2 in this study.

Recombinant human thrombopoietin promotes platelet recovery in DCAG-treated patients with intermediate-high-risk MDS/hypoproliferative AML.

This study aimed to explore the effects of recombinant human thrombopoietin (rhTPO) on platelet recovery in decitabine, cytarabine, aclarubicin, and G-CSF (DCAG)-treated patients with intermediate-high-risk myelodysplastic syndrome/hypo proliferative acute myeloid leukemia. Recruited patients were at a ratio of 1:1 into 2 groups: the rhTPO group (DCAG + rhTPO) and control group (DCAG). The primary endpoint was the time for platelets to recover to ≥ 20 × 109/L. The secondary endpoints were the time for platelets to recover to ≥ 30 × 109/L and ≥ 50 × 109/L, overall survival (OS), and progression-free survival (PFS). The time required for platelet recovery to ≥ 20 × 109/L, ≥30 × 109/L, and ≥ 50 × 109/L in the rhTPO group was significantly shorter (6.5 ± 2.2 vs 8.4 ± 3.1 days, 9.0 ± 2.7 vs 12.2 ± 3.9 days, 12.4 ± 4.7 vs 15.5 ± 9.3 days, respectively; all P < .05 vs controls). The amount of platelet transfusion in the rhTPO group was smaller (4.4 ± 3.1 vs 6.1 ± 4.0 U, P = .047 vs controls). The bleeding score was lower (P = .045 vs controls). The OS and PFS were significantly different (P = .009 and P = .004). The multivariable analysis showed that age, karyotype, and time for PLT recovery to ≥ 20 × 109/L were independently associated with OS. Adverse events were similar. This study suggests that rhTPO leads to a faster platelet recovery after DCAG treatment, reduces the risk of bleeding, reduces the number of platelet transfusions, and prolongs the OS and PFS.

Avatrombopag for the treatment of thrombocytopenia induced by chemotherapy in patients with solid tumors: A multicenter, open-label, single-arm trial.

Objective: To explore the effect and safety of avatrombopag for chemotherapy-induced thrombocytopenia (CIT). Methods: This multicenter, open-label, single-arm trial enrolled CIT patients in eight centers from October 2020 to April 2021. The participants received avatrombopag tablets 60 mg once a day for 5–10 days. The main endpoint was the proportion of patients with platelet count ≥100×109/L or increased by ≥ 50×109/L or increased by ≥ 100% in the cycle after the start of treatment. Results: Seventy-four participants were enrolled with a mean age of 59.8 ± 11.62.2% were males. The cumulative effective rate (any criteria) was 70.3% at 4 weeks. 42 (56.8%) achieved platelet count ≥100×109/L, 44 (59.5%) increased by ≥ 50×109/L, and 27 (36.5%) increase by ≥ 100% from baseline. The duration of grade III and IV platelet reduction was 4.2 ± 5.3 days. The time of PLT recovery to ≥75×109/L was 9.4 ± 6.6 days. The time of PLT recovery to ≥100×109/L was 10.2 ± 6.4 days. The platelet count nadir was 57.9 ± 45.3×109/L. The most common adverse events were nausea (8.1%), fatigue (5.4%), and abdominal pain (1.4%). There were no cases of fever, headache, or peripheral edema. Conclusion: Although it was a single-arm trial without a control group, the application of avatrombopag in patients with CIT can increase the platelet count of the patients compared with baseline. Avatrombopag is safe and tolerable. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04609891?term=04609891&draw=2&rank=1, identifier [NCT04609891]

PB2261: LINEZOLID AS A SAFE ANTIMICROBIAL AGENT IN THROMBOCYTOPENIC PATIENTS UNDERGOING CHEMOTHERAPY FOR HEMATOLOGIC MALIGNANCIES

Background: Febrile neutropenia (FN) is a common event in patients undergoing high-dose chemotherapy (HD-CT) for hematologic malignancies. Linezolid (LZ) is the first-in-class oxazolidinone antimicrobial agent active against gram-positive bacteria, often administered during FN as treatment for hospital-acquired pneumonia, gram-positive bacteriemia and soft-skin tissue infection. LZ induced thrombocytopenia or delayed platelet recovery are adverse events of concern in patients receiving HD-CT. As of today, few data are available on the safety of LZ in this specific setting. Aims: To retrospectively analyze a cohort of thrombocytopenic patients treated with LZ for FN in a single center, evaluating bleeding risk and impact on PLT recovery time. Methods: The analysis included patients diagnosed with Acute Leukemia (AL), High Grade Lymphomas (HGL) and Multiple Myeloma (MM) treated at our institution, between 2016 and 2021, with LZ for a FN episode during induction chemotherapy or ASCT conditioning. To be enrolled, PLT count at the start of LZ therapy had to be < 50×109/L. Results: A total of 40 FN episodes treated with LZ were identified. 22 occurred during induction therapy for AL and 18 during ASCT conditioning regimens. The median PLT count at the start of LZ therapy was 19×109/L in both groups (range 5-49×109/L in the AL cohort, 5-35×109/L in the ASCT group), while the median treatment duration was 8 days in both groups (range 2-15 days in the AL cohort, 3-12 days in the ASCT cohort). Only one clinically relevant bleeding event was observed in the AL group, while 0 bleeding events were observed in the ASCT group. Resolution of infection (defined as fever resolution, normalization of CRP and blood culture negativization) after the introduction of LZ therapy was observed in 17 (77%) AL patients and 15 (83%) ASCT patients. In the AML group PLT recovery (defined as a stable PLT count ≥20×109/L without the need for PLT transfusion) was observed in 18 (81%) patients with a median time to recovery of 22 days from the start of the chemotherapeutic regimen (range 18-41). PLT recovery was observed in 10 (71%) ASCT patients with a median time to recovery of 35 days from the stem cell infusion (range 13-136). 4 out of 18 patients in the ASCT group started LZ therapy after PLT recovery, and 3 out of 18 patients in the same group died due to the infectious complication that prompted the start of LZ therapy. Median PLT recovery time was not significantly different between patients enrolled in this study and historical controls from our center (AML: median 20 days, p>0.1. ASCT: median 22.5 days, p>0.1). Summary/Conclusion: Our observations support the use of LZ in this setting, as only one relevant bleeding event was observed among the two groups, and no impact on PLT recovery time was noted after comparison with historical data. Our study suggests that LZ is a safe and effective antimicrobial therapy in patients undergoing HD-CT for hematological malignancies. This data needs to be prospectively confirmed in a larger cohort of patients in a multicenter study.

Platelet concentrates preparation using a rotating membrane with Taylor vortices and axial flow

Taylor-Couette devices with a rotating filtration membrane are utilized to separate cellular components and to prepare platelet (thrombocytes, PLT) concentrate from whole blood. Due to the complicated nature of the working fluids (e.g. blood), systematic analysis is conducted to enhance the separation efficiency. Flow visualization and cell extraction techniques are applied to understand the cell distributions and classification in different flow regimes in the devices. Blood cells are found to be classified by Taylor vortices: erythrocytes (red blood cells, RBCs) and leukocytes (white blood cells, WBCs) moved toward the periphery of the vortices, while platelet remained close to the center of the vortices due to different sizes for these blood cells. The blood filtration efficiencies are evaluated using two devices at different radius ratios with a series of Reynolds number and flow rates. Operated at similar Reynolds numbers, the device can have higher filtration throughput by making a smaller inner cylinder, for comparable PLT recovery rates. An approximately 90 % recovery rate for PLT was obtained within 40 % volumetric ratio, while the ones for RBC and WBC were 75 % and 85 % respectively.

Phase I Dose-Finding Study of Eltrombopag Following High Dose Cytarabine and Mitoxantrone Chemotherapy in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Phase I Dose-Finding Study of Eltrombopag Following High Dose Cytarabine and Mitoxantrone Chemotherapy in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Atypical Hemolytic Uremic Syndrome-Clinical Presentation, Treatment, and Short Term Outcomes: The Mayo Clinic Experience

BackgroundAtypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) with an incidence of 1-2 cases per million. It is characterized by dysregulation of the alternative pathway of complement. Here we describe the clinical presentation and management of 25 patients with a diagnosis of aHUS including symptom presentation, complement serologic and genetic testing, and treatment (tx) approaches with total plasma exchange (TPE) and eculiuzmab (E).MethodsIn this retrospective study, after IRB approval, the electronic medical record was searched from 2011-2016 for patients with a clinical dx of aHUS. Inclusion criteria included: 1) presence of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia and/or pathologic evidence of TMA 2) ADAMTS13≥10%. Exclusions included 1) TMA secondary to other causes (hemolytic uremic syndrome, hypertension, scleroderma, bone marrow transplant, and medications). 2) Status post renal transplant or initial presentation to our institution for renal transplant.Results25 aHUS patients (17 female) met our criteria. Of these, 16, median 40.5 (0-66) years old received initial diagnosis and management of aHUS while hospitalized (group 1) and 9 patients, median [42 (16-70)] years, were seen in the clinic after having been previously diagnosis with TMA elsewhere (group 2). Three had surgery 6-29 days prior to clinical presentation. Procedures included total knee arthroplasty, hysterectomy, and appendectomy. Ten patients had infections (7-80) days prior to presentation. Presenting symptoms in group 1 included fever (n=2), confusion (1), seizure (1), intractable headache (3), chest pain (2), abdominal pain (6), fatigue (3), and shortness of breath (2). Laboratory evaluation is presented in Table 1 and 2. Median ADAMTS13 at presentation in group 1 was 57 (22-91)%. Complement genetic testing was completed on 88% of patients. Pathogenic complement mutations (PCM) and variants of unknown significance (VUS) were each identified in 10 patients and two had no relevant complement genetic variants identified (Table 3). Four variants in C FH, classified as VUS , were novel variants but predicted to be pathogenic by in silico analysis. Renal biopsy was available on 18 patients, all with pathologic evidence of TMA.11 patients received TPE and 10 had platelet (plt) recovery 9(1-16) days after initiation of TPE. Duration of daily TPE was 8 (1-10) days. 7 received prednisone (1mg/kg) for a total duration of 10 (1-27) days. In group 1, E was initiated in 10 patients 14(3-67 days after presentation). 5 started E despite plt recovery given worsening renal function and laboratory evidence of MAHA. In group 2, 8 were treated with E. 5 were started on E 43-187 days prior to initial visit while 3 were started on E at the visit because of worsening renal function. 77.8% of patients started on E had a PCM or VUS.6 patients in groups 1 and 2 had neurological symptoms including vision changes (1), seizure (3), stroke (2), and posterior reversible encephalopathy syndrome (3). 15 required hemodialysis (HD). At last follow up (fu), 10/18 patients remained on E and 5 of these had fu 4 (1.63-55.8) months after initial presentation. Of those still on E, 5/ 9 remained on HD at last fu. Two underwent renal transplant (one had relapsed after stopping E and one in a patient whose renal function did not improve despite E). Of those alive, 7 discontinued E with total duration of tx ranging from < 1 month to 6 months (Figure 1). In those discontinuing E, 50% stopped HD with total HD duration of 3-31 days. There was one relapse in fu time. Of 25 patients, there were two deaths within acute tx of aHUS and two additional deaths during fu.ConclusionaHUS has a heterogeneous clinical presentation and response to tx. Complement serology in our study were variable, however complement serology was not always assessed prior to tx. PCM were present in 10 patients and 4 novel VUS in CFH were noted. Though TPE resulted in plt recovery in 91% of cases, it was not always sufficient for reversal of end organ damage. Addition of E led to renal recovery in 53% of those requiring HD. [Display omitted] DisclosuresWinters:Grifols International SA: Consultancy; Eliaz Therapeutics Inc: Membership on an entity's Board of Directors or advisory committees; Wiley Blackwell: Employment; Sanofi Inc: Other: Moderated opinion leader's forum; Fresenius Kabi USA: Consultancy; Mayo Clinic: Employment; Regional Health Inc: Consultancy.

The Association between CD34+ Dose, Platelet Recovery and Incidence of Relapse after Autologous Stem Cell Transplant in Multiple Myeloma

Autologous hematopoietic stem cell transplantation (ASCT) after melphalan (Mel) conditioning has been shown to improve outcomes in patients (pts) with multiple myeloma (MM), including complete response (CR), disease free and overall survival (OS). Successful collection and subsequent stem cell rescue with adequate number of CD34+ stem cells are key to achieving these goals, including reduced platelet (plt) engraftment times and lower cumulative incidence of relapse (CIR). However, there has been some discordance regarding the optimal CD34+ dose and the effect of the cell dose on the time to plt engraftment, dependency on plt transfusion in the post-ASCT period, and subsequent CIR.A retrospective analysis of 275 consecutive MM patients who underwent ASCT between 2010-2017 at a single institution was performed to determine the relationship between CD34+ stem cell infusion dose and plt recovery, dependence on plt transfusion in the post-ASCT period as well CIR. Platelet recovery was defined by the first of the 3 consecutive days with plt count ≥ 20 x 109/L while remaining transfusion free for 7 preceding days. Analyses were done separately by age groups (< 65 years and ≥ 65 years) and by Mel conditioning received (140 mg/m2 vs. 200 mg/m2). The Mann-Whitney test was used to compare the median plt engraftment times and dependence on plt transfusions between the groups with < 2.5 vs. ≥ 2.5 x 106 (mill) CD34+ cells/Kg infused; Fisher's exact test was used to assess the effect on achieving plt recovery; Gray's test was used to compare CIR curves; log-rank test was used for comparisons of OS curves. CIR was defined as the probability of having had a relapse after achieving a response with death without experiencing a relapse as a competing event.Overall, there were 79 pts age ≥ 65 (median 68, range 65-75) and 196 pts age < 65 (median 58, range 34-65). Median time in days (d) to engraftment of plts was shorter for pts who received ≥ 2.5 mill (median 3.3, range 2.5-19.9) vs. < 2.5 mill cells/Kg (median 2.2, range 0.8-2.4): 24 vs. 25 d in both age groups < 65 and ≥ 65 years (p=0.0005 and 0.036, respectively). Patients who received < 2.5 vs. ≥ 2.5 mill CD34+ cells/Kg also required at least 1 plt transfusion vs. none, in both age groups (p=0.048 and 0.022, respectively). CIR was statistically different among the 4 groups analyzed (age<65/CD34+<2.5 vs. age<65/CD34+≥2.5 vs. age≥65/<2.5CD34+ vs. age≥65/CD34+≥2.5, p=0.015): the lowest 3 year CIR of 26% was seen in age<65/CD34+≥2.5 group, and the highest 52% in age≥65/<2.5CD34+ group. Median hospital stay, OS or disease response [CR vs. partial response (PR)] at day +100 were not statistically different amongst the two groups, regardless of the CD34+ stem cell dose infused, or the age group analyzed.Overall, there were 74 and 201 pts who received 140 mg/m2 vs. 200 mg/m2 of Mel conditioning, respectively. While there was no statistical difference in plt transfusion requirement in Mel140 mg/m2 pts with respect to the CD34+ cell dose (p=0.069), Mel 200 mg/m2 pts who received < 2.5 vs. ≥ 2.5 mill CD34+ cells/Kg required longer plt engraftment time (25 vs. 24 d, respectively, p=0.001). Patients who received < 2.5 vs. ≥ 2.5 mill CD34+ cells/Kg also required at least 1 platelet transfusion vs. none, in both Mel 140 mg/m2 vs. Mel 200 mg/m2 groups (p=0.047 and 0.001, respectively). CIR was statistically different among the 4 groups analyzed (Mel140/CD34+<2.5 vs. Mel140/CD34+≥2.5 vs. Mel200/<2.5CD34+ vs. Mel200/CD34+≥2.5, p=0.005, Figure 1.): the lowest 3 year CIR of 4% was seen in Mel140/CD34+≥2.5 group, and the highest 27% in Mel200/CD34+<2.5 group. Median hospital stay, OS or disease response (CR vs. PR) at day +100 were not statistically different among the two groups, regardless of the CD34+ stem cell dose infused, or the Mel conditioning received.Our single institution experience suggests that infusion of ≥ 2.5 mill CD34+ cells/Kg in both age groups, or with Mel200 mg/m2 conditioned patients is a more optimal CD34+cell dose for ASCT in MM that shortens platelet reconstitution, and reduces the need for plt transfusions in the post-ASCT period. The same CD34+ cell dose also argues for the lower rates of CIR, where it appears to abrogate the effects of lower Mel conditioning. These curious findings which imply yet unelucidated stem cell graft influence require further analysis and replication in larger cohorts, while for now they may serve to instruct stem cell collection practices for ASCT in MM. [Display omitted] DisclosuresBaljevic:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Holstein:Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees. Lunning:Celgene: Consultancy; BMS: Consultancy; Genentech: Consultancy; Spectrum: Consultancy; Onyx: Consultancy; TG Therapeutics: Consultancy; Gilead: Consultancy; Juno: Consultancy; Epizyme: Consultancy; AbbVie: Consultancy; Pharmacyclics: Consultancy.

Fludarabine Melphalan Conditioning Followed By T-Replete Haplo Identical (Haplo) Transplantation or Haplo Cord (HC) Transplantation

The use of mismatched donors is rapidly increasing for pts with hematological malignancies in need of allo HCT. Here we compared the outcomes of melphalan based reduced-intensity conditioning (RIC) using haplo-identical transplantation with post transplant cyclophosphamide (PTCy) and haplo cord transplantation where a CBU graft is supplemented with CD34 selected haplo-identical cells to accelerate engraftment.Patients and Methods:217 pts underwent Haplo transplants at MDACC. Conditioning consisted of fludarabine (flu)-melphalan 140 mg/m2 (mel) (47) flu-mel-thiotepa (129), or flu-mel-TBI 200 cGy (37). Dose of Mel was 140 mg/m2 for 128 and 100 mg/m2 for 88.GVHD prophylaxis was PTCy, tacro and mycophenolate (MMF). Graft source was bone marrow in 206 pts and PBSC in 11. 224 pts underwent HC HCT at Weill Cornell, New York and at the University of Chicago. Conditioning consisted of Flu-Mel (178) or Flu-Mel-TBI 400 cGy (46). Dose of Mel was 140 mg/m2. GVHD prophylaxis was ATG, tacro and MMF. Pt characteristics are in Table 1. 58% of haplo vs 67% of HC recipients had AML or MDS (P=0.01). 36% of HC vs 20% of Haplo were 60 and older (P=0.007) and 56% of HC vs 34% of Haplo had HCTCI >=3 (P=0.0000). Median F/U was 30 mo for HC vs 21 mo for Haplo group.ResultsMedian time to neutrophil recovery was 11 days after HC vs 19 after Haplo SCT (p<0.001). Time to plt recovery was 22 d after HC vs 26 Haplo SCT (p =0.001). CI of gr II-IV aGVHD was 21% by d150 after HC vs35% after Haplo SCT (p=0.0005). CI of gr III-IV aGVHD was identical at 11% in each group. CI of all chronic GVHD was 2% at one year after HC vs 16% after Haplo SCT (p<0.001). Overall survival, PFS, CI Relapse and NRM were not significantly different. In multivariable analysis, graft source did not correlate with OS, PFS, Relapse or NRM. In multivariable analysis Disease Risk Index (DRI) and Age>=60 were the major determinants of OS and PFS. For patients with Low and Intermediate DRI under age 60, 2 Y OS was 60% for haplo and 59% for HC.Conclusions: Melphalan based RIC result in similar and encouraging survival and progression free survival with HC or haplo grafts. HC HCT was associated with more rapid neutrophil and a lower rate of acute and of chronic GVHD. [Display omitted] DisclosuresLiu:Karyopharm: Research Funding; BMS: Research Funding.

Abo不相容性和抗a / B异凝集素滴度对血液恶性肿瘤清髓处理后输血需求和无关脐带血移植的早期结果的影响

Abstract Background:ABO incompatibility is not considered a main contraindication to allogeneic hematopoietic stem cell transplantation (aHSCT). However, it has been associated with a number of immunohematological complications. The effects of ABO incompatibility on aHSCT remain controversial.The change of isoagglutinin titers and early clinical outcomes were analyzed after unrelated cord blood transplantation (UCBT) with ABO-incompatibility donor. Methods:252 patients with hematological malignant diseases and other hematological disorders who underwent unrelated UCBT from January 2019 to April 2020 were retrospectively analyzed in this research. Patients were studied in identical, major, minor and bidirectional mismatch groups. Immunoglobulin m (IgM) isoagglutinin titers were tested one day before the transplant (-1 day), 2 weeks post-transplant, 4 weeks post-transplant and 6 weeks post-transplant. R esults:76 match,71 major mismatch, 70 minor mismatch and 35 bidirectional unrelated UCBT were identified. The median neutrophil, PLT and red blood cell (RBC) recovery days were 18, 38 and 22, respectively. ABO mismatch did not influence the neutrophil, PLT and RBC engraftment. The median of RBC transfusion in 30 days were 5 units and PLT were 6 units. There were no statisitcal difference in 0-30 days RBC and PLT transfusion after UCBT. 31-100 days transfusion was similar to in 30 days transfusion. No patients developed pure red cell anemia (PRCA). -1day IgM titers ≥1:16 did not develop higher risk of grade II-IV aGVHD when compared with titers≤1:8 group. However, we detected a marginal higher PLT transfusion in 30 days after transplant at antibody titers ≥1:16 group when compared with titers≤1:8 (P=0.051). In the major and bidirectional groups, we found that group O IgM anti-donor antibodies were displayed a significant higher than the group B anti-A titer (p&amp;lt;0.001) in setting the time one day before the transplant, but no significant with group A. 2 weeks after the transplant, group B anti-A was still showed significant lower than the group O anti-A (p&amp;lt;0.001). 4 weeks after the UCBT, we observed a modest, but no statistical significant lower titers of group B anti-A antibodies as compared with O group (P=0.097). 6 weeks after the transplant, there were no statistical significant among group O, A and B. In the multivariable Cox regression model, transfusion of ≥5 RBC units in 30 days after UCBT (HR=1.727, 95%CI=1.020-2.926, P=0.042) and PLT engraftment ≥38 days (HR=1.964, 95%CI=1.134-3.401, P=0.016) were correlated to greater risk of grade severe aGVHD. Conclusion:This study showed that ABO mismatch did not influence the neutrophil, PLT and RBC recovery time.Group O IgM anti-donor isoagglutinins in recepients showed a higher titers than the group B in setting with the time (-1 days pre-transplant, 2 weeks post-transplant, 4 weeks post-transpant). Pre-transplant higher anti-donor isoagglutinins were associated with more PLT transfusion requirements after UCBT. More RBC transfusion (≥5 units) and longer PLT recovery time (≥38 days) showed a higher incidence of severe aGVHD. Disclosures No relevant conflicts of interest to declare.

A Single-Arm, Open-Label Phase 1 Study of Itacitinib (ITA) with Calcineurin Inhibitor (CNI)-Based Interventions for Prophylaxis of Graft-Versus-Host Disease (GVHD; GRAVITAS-119)

A Single-Arm, Open-Label Phase 1 Study of Itacitinib (ITA) with Calcineurin Inhibitor (CNI)-Based Interventions for Prophylaxis of Graft-Versus-Host Disease (GVHD; GRAVITAS-119)

Factors Associated with Impaired Hematopoietic Recovery after CD19-Targeted CAR-T Cell Therapy

<h3>Introduction</h3> Despite promising results in patients with relapsed/refractory B cell malignancies, CD19 CAR-T cell therapy can be associated with significant toxicities. Specifically, impaired hematopoietic recovery can be observed in a subset of patients. <h3>Objectives</h3> We aimed to describe hematopoietic recovery following CD19 CAR-T cell therapy, and to identify factors independently associated with this complication using multivariable modeling. <h3>Methods</h3> We retrospectively analyzed 125 adult patients with R/R acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL), treated with CD19 CAR-T cells on a phase 1/2 clinical trial (characteristics summarized in Table 1). Criteria for neutropenia, thrombocytopenia, and recovery were defined as per the CIBMTR reporting guidelines. For competing risk analysis, an event was defined as ANC or platelet (Plt) recovery, with death, new cytotoxic therapy, relapse with marrow involvement in the absence of ANC or platelet recovery considered as competing events. Patient, disease, and CAR-T cell therapy-related variables were included in multivariable analyses. <h3>Results</h3> ANC and Plt recovery after CD19 CAR-T cell therapy were observed in 91% (ALL, 86%; CLL, 92%; NHL, 95%) and 86% (ALL, 86%; CLL, 86%; NHL, 84%) of patients, respectively. Median time to ANC recovery was 9 days and the probability of ANC recovery at day 28, 60, and 90 was 80% (95%CI, 73-87), 86% (95%CI, 80-92) and 89% (95%CI, 83-94), respectively. The probability of platelet recovery on the day of CAR-T cell infusion was 55% (95%CI, 46-64); rising to 74% (95%CI, 67-82), 83% (95%CI, 76-90), and 84% (95%CI, 77-90) on days 28, 60, and 90, respectively. A competing event was always observed in patients without ANC or Plt recovery. In multivariable analysis (Table 2), higher pre-lymphodepletion (LD) Plt count and higher peak CD8+ CAR-T cells in blood were associated with faster ANC recovery. A diagnosis of ALL was associated with slower ANC recovery. (CLL vs ALL, HR=1.60, p=0.02; NHL vs ALL, HR=2.07, p=0.007). Higher CRS grade was also associated with slower Plt recovery (HR=0.67 per grade increase, p<0.001). Higher pre-LD Plt count (HR=1.08 per 25 × 10⁹/L increase, p=0.001) and higher peak CD8+ CAR-T cell in blood (HR=1.41 per log₁₀ cells/µL increase, p<0.001) were associated with faster Plt recovery. Figure 1 shows cumulative incidence of ANC and Plt recovery by CRS grade. <h3>Conclusion</h3> We observed impaired ANC and Plt recovery in a significant fraction of patients undergoing CD19 CAR-T cell therapy. Moreover, we identified factors independently associated with impaired hematopoietic recovery: disease type, prelymphodepletion Plt count, in vivo CAR-T cell expansion, and CRS grade. In addition to providing a benchmark for future CAR-T cell research, our findings suggest CRS prevention might improve hematopoietic recovery after CD19 CAR-T cell therapy.

Severe Cytokine Release Syndrome Is Associated with Impaired Hematopoietic Recovery after CD19-Targeted CAR-T Cell Therapy

Background Chimeric antigen receptor therapy (CAR-T) directed against CD19 has demonstrated efficacy in patients with relapsed/refractory (R/R) B-cell malignancies. Delayed hematopoietic recovery with grade 3/4 neutropenia and thrombocytopenia, requiring extended growth factor administration or transfusions, has been observed in patients undergoing CAR-T cell therapy, although the factors influencing recovery are poorly understood. In this study, we performed multivariable analyses to identify factors associated with hematopoietic recovery in patients undergoing CD19 CAR-T cell therapy. Methods We retrospectively analyzed 125 patients with R/R acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL), treated with CD19-targeted CAR-T cells on a phase 1/2 clinical trial in our institution (NCT01865617). Patients receiving more than one CAR-T infusion were excluded. Criteria for neutropenia, thrombocytopenia, and recovery were defined as per the Center for International Blood and Marrow Transplant Research (CIBMTR) reporting guidelines: neutropenia, absolute neutrophil count (ANC) ≤ 500/mm3; thrombocytopenia, platelet (Plt) count ≤ 20 x 109/L; neutrophil recovery, ANC &gt; 0.5 x 109/L for three consecutive laboratory values obtained on different days irrespective of growth factor administration; platelet recovery, Plt &gt; 20 x 109/L for three consecutive values obtained on different days in the absence of platelet transfusion for seven days. For competing risk analysis, an event was defined as having achieved ANC or Plt recovery, with the following considered as competing events: death, new cytotoxic therapy, relapse with marrow involvement in the absence of ANC or platelet recovery. Patients who never met the CIBMTR criteria for neutropenia of thrombocytopenia were considered as having recovered at time = 0. To identify factors associated with impaired hematopoietic recovery after CD19 CAR-T cell therapy, patient-, disease- and CAR-T cell therapy-related variables were included in a multivariable Fine and Gray model prior to variable selection using LASSO penalization (Table 2 footnote). Results We included 125 patients (ALL, n=44; CLL, n=37; NHL, n=44) with a median age of 55 (range, 20-76). Patients were heavily pre-treated with a median of 4 prior therapies (range, 1-10); 31% had undergone prior autologous or allogeneic hematopoietic cell transplantation (HCT). Median ANC and Plt prior to lymphodepletion were 2 x 109/L (range 0-23) and 112 x 109/L, range 3-425), respectively. Patient and treatment characteristics are summarized in Table 1. ANC and Plt recovery after CD19 CAR-T cell therapy were observed in 91% (ALL, 86%; CLL, 92%; NHL, 95%) and 86% (ALL, 86%; CLL, 86%; NHL, 84%) of patients, respectively. Median time to ANC recovery was 9 days and the probability of ANC recovery at day 28, 60, and 90 was 80% (95%CI, 73-87), 86% (95%CI, 80-92) and 89% (95%CI, 83-94), respectively. The probability of platelet recovery on the day of CAR-T cell infusion was 55% (95%CI, 46-64); rising to 74% (95%CI, 67-82), 83% (95%CI, 76-90), and 84% (95%CI, 77-90) at day 28, 60, and 90, respectively. A competing event was always observed in patients without ANC or Plt recovery. In multivariable analysis, higher pre-lymphodepletion Plt count (HR=1.08 per 25 x 109/L increase, p=0.006) and higher peak CD8+ CAR-T cells in blood (HR=1.47 per log10 cells/µL increase, p&lt;0.001) were associated with faster ANC recovery. ALL diagnosis and higher cytokine release syndrome (CRS) grade were associated with slower ANC recovery (CLL vs ALL, HR=1.60, p=0.02; NHL vs ALL, HR=2.07, p=0.007). Higher CRS grade was also associated with slower Plt recovery (HR=0.67 per grade increase, p&lt;0.001). Higher pre-lymphodepletion platelet count and higher peak CD8+ CAR-T cell in blood were associated with faster platelet recovery (HR=1.08 per 25 x 109/L increase, p=0.001; HR=1.41 per log10 cells/µL increase, p&lt;0.001). Of note, lymphodepletion intensity did not seem to affect hematopoietic recovery. Table 2 summarizes the results of the multivariable analysis. Figure 1 shows ANC and Plt recovery by CRS grade. Conclusion We identified CRS grade as independently associated with impaired hematopoietic recovery after CD19 CAR-T cell therapy. Our findings suggest that the prevention of CRS may improve hematopoietic recovery after CD19 CAR-T cell therapy. Figure Disclosures Hirayama: DAVA Oncology: Honoraria. Maloney:Celgene,Kite Pharma: Honoraria, Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; Juno Therapeutics: Honoraria, Patents &amp; Royalties: patients pending , Research Funding; A2 Biotherapeutics: Honoraria, Other: Stock options . Turtle:Caribou Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Other: Ad hoc advisory board member, Research Funding; Allogene: Other: Ad hoc advisory board member; Novartis: Other: Ad hoc advisory board member; Juno Therapeutics: Patents &amp; Royalties: Co-inventor with staff from Juno Therapeutics; pending, Research Funding; Precision Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; T-CURX: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Other: Ad hoc advisory board member; Humanigen: Other: Ad hoc advisory board member.

A Single Arm, Phase II Study of Eltrombopag to Enhance Platelet Count Recovery in Older Patients with Acute Myeloid Leukemia (AML) Undergoing Remission Induction Therapy

A Single Arm, Phase II Study of Eltrombopag to Enhance Platelet Count Recovery in Older Patients with Acute Myeloid Leukemia (AML) Undergoing Remission Induction Therapy

Five Active Components Compatibility of Astragali Radix and Angelicae Sinensis Radix Protect Hematopoietic Function Against Cyclophosphamide-Induced Injury in Mice and t-BHP-Induced Injury in HSCs.

Although the compatibility of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) has favorable effect on promoting hematopoiesis in traditional Chinese medicine (TCM), the main active components and pharmacological mechanism are unknown. We investigated the five active components and its mechanisms in vitro and in vivo. Five active components of Astragalus glycosides (AST), Formononetin (FRM), Ferulic acid (FRA), Calycosin (CAL), and Calycosin-7-glucoside (CLG), which could be absorbed in intestinal tract, were detected in this study. The peripheral blood, hematopoietic growth factors (HGFs), and hematopoietic progenitor cells (HPCs) colony were observed to evaluate the effect of these five active components promoting hematopoiesis. Furthermore, hematopoietic stem cell (HSC) proliferation, aging, cycle, and related proteins were detected to explore the mechanism of these five components promoting HSC proliferation. i) The in vivo experiments showed that the combination of the five active components could remarkably increase the number of RBCs, WBCs, PLTs, and content of Hb in peripheral blood and the area of bone marrow hematopoietic tissue, as well as thrombopoietin (TPO), erythropoietin (EPO), granulocyte-macrophage colony stimulating factor (GM-CSF), and colony of CFU-GM, CFU-MK, CFU-E, and BFU-E in serum. Each of these five components promoted the recovery of RBCs and Hb, and increased TPO, CFU-MK, and CFU-E. All components except for AST increased the CFU-GM. FRA increased the number of WBCs, the area of bone marrow hematopoietic tissue, and BFU-E. FRA and AST promoted PLT recovery. FRA and CAL improved the content of GM-CSF. FRA, CAL, and CLG improved the content of EPO. ii) The in vitro experiments showed that FRA, FRM, and AST significantly promoted cell proliferation, reduced the positive rate and G0/G1 cells, and increased G2/M + S cells and the expression of cyclin D1 and CDK4 proteins in aging HSCs. Furthermore, the combination of five components had the best effect. Taken together, the five active components of AST, FRM, FRA, CAL, and CLG were the main pharmacodynamic substances of the AR-ASR compatibility, which promoted hematopoiesis. The combination of them had a synergistic effect. The mechanism of promoting hematopoiesis may be relevant to regulating cyclin-related proteins, promoting cell cycle transformation, and promoting HSC proliferation.

PB2372 THE CORRELATION AND PREDICTIVE VALUE OF IMMATURE PLATELET FRACTION TO PLASMA PLATELET RECOVERY IN PATIENTS RECEIVING AUTOLOGOUS STEM CELLS TRANSPLANTATION

Background: Engraftment is a critical milestone of the hematopoietic stem cell transplantation process. The immature platelet fraction (IPF) are considered early indicators of bone marrow recovery. Aims: The objective of this study was to assess this parameter as predictors of autologous stem cell transplantation. Methods: The cross-sectional study was conducted at Ampang Hospital from June 2016 to January 2019, and included 30 autologous transplant patients with various hematologic malignancies. The results of post-transplant IPF and PLT were traced from the hematology laboratory, and validated by a hematologist before analysis. The role of IPF towards post-transplant PLT recovery was investigated by using parameters such as transient increase in IPF (%), time to transient increase in IPF (days), and 7 days mean IPF (%), towards PLT engraftment (days), lowest PLT, time to lowest PLT (days), PLT recovery (%), and PLT recovery time (days) from transplant day and lowest PLT. The degree of correlation was determined based on the Cohen's convention (1988). Patients with incomplete results (more than 50% missing data) were excluded from the analysis. Results: The median age of the cohort was 37 years, ranging from 18 to 67 years. The conditioning regimens used for autologous transplant included BEAM (69.6%), high dose melphalan (21.7%) and Bu/TT/Cy (8.7%). The mean of PLT engraftment was 11.4, ranging from 10.7 – 12.0 days after autologous transplantation. The cohort presented a mean value of 5.43% for transient increase in IPF, 4.7 days for time to transient increase in IPF, and 3.67% for 7 days IPF. The mean values in relation to PLT recovery were 14.40 × 109/L for lowest PLT, 5.3 days for time to lowest PLT, 225% for PLT recovery, and 6.9 days for PLT recovery time from transplant day and 1.7 days for PLT recovery time from lowest PLT. Statistically significant and positive correlations were found in the transient increase in IPF towards the PLT recovery time from the lowest PLT achieved in transplant patients (r = 0.6141, p = 0.0114); in the transient increase in IPF towards the PLT recovery time from transplant day (r = 0.6028, p = 0.0135); in post-transplant 7 days mean IPF towards the PLT recovery time from the lowest PLT achieved in transplant patients (r = 0.7450, p = 0.0014). A negative correlation was found in the time to the transient increase in IPF towards the PLT recovery time from the lowest PLT (r = –0.5245,p = 0.0370). The degree of the above correlations were considered strong (|r| > 0.5). Summary/Conclusion: The generation and release of IPF, as part of hematopoietic activity seemed to be predictive and correlated with the PLT recovery time. A transient increase in the IPF preceded the PLT recovery by approximately 2 days and may be used to predict PLT recovery in patients receiving autologous transplantation. The longest time to have a transient increase in the IPF, the shortest time required for PLT to bounced back from its lowest level.

Analysis of Curative Efficacy of Different Chemotherapy Regimen Combined with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation on Multiple Myeloma

To evaluate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) on patients with multiple myeloma( MM) after Sequential different chemotherapy. Seven cases of patients with MM were included in the A group, and 14 cases of patients received 4-6 courses of chemotherapy with VAD and MP before transplantation were included in the B group and received 4-6 courses of chemotherapy with VTD and VD before transplantation. Auto-peripheral blood hematopoietic stem cell were mobilized by G-CSF. Condition regimen were melphalan(A group) or bortezomib combined melphalan(B group). IFN-α(A group) or Thalidomide(B group) was used as maintenance treatment after auto-PBHSCT. Two cases of patients reached to complete remission (CR)(2/7,28.6%),1 case got very good partial remission (VGPR) (1/7,14.3%), 4 cases got partial remission(PR) (4/7,57.1%) in A group, and 9 cases got CR (9/14,64.3%), 3 cases got VGPR(3/14,21.4%), and 2 cases got PR(2/14,14.3%) in the B group before auto-PBHSCT. The CR and VGPR were significant difference between 2 groups (P<0.05). All the patients got hematopoietic recovery. In 2 groups, the median time of ANC recovery≥0.5×109/L was 13 (11-16) and 14（11-18）days, that of WBC recovery ≥4.0×109/L were 16(15-19) and 18(16-20)days, Plt recovery ≥ 50 ×109/L was 21 (18-25) and 21(17-25) days. Bone marrow showed CR in 21 to 28 days after transplantation. All of 7 cases of patients remised in 6 to 47 months after transplantation, and 4 cases died lastly and 3 cases failed to be followed up in A group. The median time of progression-free survival(PFS) was 36(6-47) months, and that of overall survival(OS) was 37(7-50) months. In B group, 2 cases of patients remissed in 5 and 17 months after transplantation, and did lastly, 1 case relieved in 12 months after transplantation and failed to be followed up. 1 case of patient relived in 46 months after transplantation, and then received the second auto-PBHSCT, and got CR for 105 months. Other 10 cases got CR, their median time of PFS was 45.5(4-105) months, the median time of overall survival(OS) was 45.5(4-105) months. The PFS and OS were very significant different between 2 groups (P<0.01). Bortezomib-based chemotherapy, Auto-PBHSCT and maintenance treatment with thalidomide were favorable to the patients of MM for survival prolongation.

A Novel Recombinant Human Thrombopoietin Therapy for Promoting Platelet Engraftment in Haematological Malignancies after Single Umbilical Cord Blood Transplantation: A Prospective Randomized Controlled Trial

▪Background: Umbilical cord blood transplantation (UCBT) is an alternative to matched-unrelated or mismatched-related peripheral blood (PB) or BMT and has emerged as a widely accepted treatment for a wide variety of hematologic malignancies. However, delayed platelet engraftment (DPE) and platelet engraftment failure still remain the common problems following UCBT. So far, no standard therapy has been recommended. A few studies have demonstrated that recombinant human thrombopoietin (rHuTPO) could play an effective role in advancing platelet recovery after allo-HSCT. Nevertheless, it remains unknown whether rHuTPO plays the same role while it is applied in UCBT. We designed this prospective randomized controlled trial with the purpose of determining whether rHuTPO improves platelet engraftment in patients undergoing single UCBT(sUCBT) and further evaluating the function of rHuTPO in sUCBT.Methods: We enrolled 120 patients with haematological malignancies between October 2016 and March 2018 undergoing sUCBT in Department of Hematology, the First Affiliated Hospital of University of Science and Technology of China. This study was supported by National Natural Science Foundation, China (81670165) and International Cooperation Projects of Anhui Province, China(1804b06020352). The trial was approved by the Medical Ethics Committee of the First Affiliated Hospital of University of Science and Technology of China, and registered on www.chictr.org.cn(ChiCTR-IPR-16009357). 60 patients were randomly assigned into the experimental group, in which they received rHuTPO on Day 14 after sUCBT with a dose of 300 U/kg once daily for a period of 14 days; the remaining 60 patients formed the no-treatment control group. Among 120 patients, 19 received total body irradiation (TBI) based conditioning and others received modified myeloablative conditioning without antithymocyte globulin (ATG) as myeloablative conditioning. All patients were given cyclosporin (CsA) and mycophenolate mofetil (MMF) preventing graft-versus-host disease (GVHD). Supportive care and other treatments, including infectious disease prophylaxis and the use of granulocyte colony-stimulating factor, were provided following our center's protocols.Results: With a median follow-up of 336 days (ranging between 96-618) for the surviving patients, the cumulative incidence of PLT engraftment in the rHuTPO group (89.7%, 95% confidence interval [CI], 77-95.5) was significantly higher than that in the control group (78.9%, 95%CI, 65.3-87.6) (p=0.0294); the median time of PLT engraftment was 35 and 40days (ranging between 18-144 and 19-170 respectively, P=0.155). The median time of PLT recovery in the rHuTPO group was 43days(ranging between 25-171days), which was significantly shorter than that in the control group(53days, ranging between 28-195, P=0.034). The rHuTPO group also showed an advantage over the control group in infused PLT units (6 vs 8, p=0.0294). The cumulative incidence of ANC engraftment was 98.3% (95% CI, 75.2-99.9) and 94.9% (95% CI, 83.8-98.5) (p=0.111) respectively in two groups.Multivariate analysis confirmed the significance of differences in platelet engraftment between two groups. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease (GVHD),relapse,non-relapse mortality (NRM) and cytomegalovirus viremia and the probabilities of overall survival(OS) and leukemia free survival (LFS) did not differ between the two groups. No severe adverse effects were observed in all patients.Conclusions: Our results demonstrate that rHuTPO could noticeably improve platelet engraftment and promote platelet recovery in patients with haematological malignancies receiving sUCBT; in the meantime, it could also reduce the requirement for platelet transfusion. This study indicated that rHuTPO could be a good option for promoting platelet engraftment and recovery in haematological malignancies after sUCBT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Gene Therapy for Sickle Cell Anemia Using a Modified Gamma Globin Lentivirus Vector and Reduced Intensity Conditioning Transplant Shows Promising Correction of the Disease Phenotype

▪Background: Genetic transfer of an anti-sickling β87-globin lentiviral vector (LV) into hematopoietic stem cells (HSC) followed by myeloablative transplant has cured one child with sickle cell anemia (SCA) (NEJM 2017), although it was not successful in 7 subsequent adult SCA patients, and modifications to intensify ablative conditioning, improve HSC dose, gene transfer are underway (Blood 130 Suppl 1: 527, 2017). Based upon our preclinical data (Blood 2009), we embarked upon a Reduced Intensity Conditioning (RIC) Phase I/II Pilot Study on Gene Transfer in Patients with SCA with a modified γ-Globin LV (NCT02186418), hypothesizing this approach will be safe, feasible and efficacious; Moreover, RIC will have significantly less toxicity, costs, and be implementable in many transplant centers, including those in some of the resource-poor countries, where supportive therapies for myeloablative transplants are unavailable, and where majority of SCA patients exist.Methods: Adult patients with severe SCA deemed eligible were transfused/erythrocytapheresed prior to HSC collection and transfused for 6 months post-transplant (PT) to Hb>10g/dl and HbS~30%. CD34+ HSC were collected via bone marrow harvest (BMH) and/or plerixafor mobilized Peripheral Blood Stem Collection (PBSC), selected for CD34+ cells and transduced. Patients received a single dose of IV melphalan (140mg/m2 BSA) 36hr prior to infusion of γ-globin modified (GM)-HSC. Patients were monitored for adverse events (AE), engraftment, vector copy number (VCN), modified HbF (HbF*) expression and clinical features of SCA.Results: Two SCA patients (35yo and 25yo) with HbS-β0 thalassemia genotype were treated. CD34+ HSC were collected via multiple BMH (P1) and BMH+PBSC (P2). Follow up data are available for 6 and 12mo on P1 and P2. P1 received 1x106 CD34+ cells/kgbw [vector copy number (VCN) 0.22], and P2 received 6.9x106 CD34+ cells/kgbw [VCN 0.46]. Time to neutrophil engraftment (ANC ≥ 500) was day 9 and 7 post-transplant (PT) in P1 and P2, respectively, and time to Plt recovery (Plt>50K) was day 14 PT in both. Patients included in this trial had severe disease and continued to have pre-existing chronic pain requiring significant opiates; hence ~80% of the AEs were pain events; other AEs were anticipated transient laboratory AEs associated with melphalan. Following GM-HSC infusion, both patients showed a progressive rise in HbF* (a point mutation in the γ-globin LV allows distinction from endogenous HbF by HPLC) starting from day 30 PT. Since patients had transfused HbA containing RBCs in the initial 6 months, HbF*/(HbF*+HbS) was calculated, and was 20% and 21% in P1 and P2 at day 180 PT and VCN 0.2-0.4, detected in all lineages. Integration site analysis, performed on the infused products (Day 0), at day 30 PT on P1 and P2, and on day 180 PT on P1 demonstrated highly polyclonal pattern of integration. At 1 yr PT, P1 had 20% HbF* (2.1g/dl HbF*, total Hb 10.6) with a stable VCN of 0.2-0.4 in multiple lineages in bone marrow and peripheral blood. The baseline Hb of P1 was 7.5-8.5g/dL prior to transplant. In the preceding 2 years prior to transplant, both patients were admitted for pain crises/acute chest >5-6 times/yr, and had chronic pain requiring chronic opiates. Chronic pain persisted for 4-5 months PT in P1, after which P1 has not required IV opiates, negligible oral opiates and has had no hospital visits/admissions with acute sickle events. P2 has required decreasing amounts of oral opiates for chronic back pain.Conclusions: Early results from 2 SCA adults treated with a modified γ-globin LV modified autologous HSC following RIC transplant showed excellent safety, feasibility, with minimal post-transplant toxicity, rapid count recovery, and sustained stable genetically modified cells in peripheral blood and bone marrow. The first patient shows significant clinical amelioration of the SCA phenotype at 1 year PT, with 20% vector-derived HbF (HbF*) that has caused amelioration of anemia, near elimination of chronic pain and absence of acute sickle events. The second patient, although still early post-transplant shows a similar HbF* trajectory. Additional study data will demonstrate whether this level of HbF* will provide consistent clinical benefit to patients with severe SCA. These early results, especially following a RIC transpant, are extremely promising; and if sustained, will provide a ‘transportable’ safe and feasible gene therapy for SCA. DisclosuresMalik:CSL Behring: Patents & Royalties. Quinn:Global Blood Therapeutics: Research Funding; Silver Lake Research Corporation: Research Funding; Amgen: Research Funding.

Recombinant human interleukin-11 for chemotherapy-induced thrombocytopenia of acute leukemia: a multi-center study

Objective To explore the efficacy and safety of recombinant human interleukin-11 (rhIL-11) in treatment of chemotherapy-induced thrombocytopenia of acute leukemia. Methods Acute leukemia patients with chemotherapy-induced thrombocytopenia [Platelets (Plt) < 50×109/L] in 6 centers nationwide from February 2016 to July 2016 were treated with rhIL-11 (2 mg/time, twice per day) by subcutaneous injection. Treatment lasted 7 days or at least until Plt≥ 50×109/L. The Plt recovery was observed during treatment. Results A total of 112 patients were enrolled, and 2 patients decided to drop out of study. The efficacy population consisted of 110 patients, and the total response rate reached 74.5% (82/110). The average variation of Plt during treatment was (70±54)×109/L, and recovery average time of Plt for the patients with favorable efficacy was (8.7±3.0) days. In treatment with severe thrombocytopenia, rhIL-11 alone could shorten the recovery time compared with rhIL-11 combined with Plt transfusion [(8.0±2.6) d vs. (9.6±3.5) d, t=2.17, P=0.03]. Conclusion rhIL-11 twice a day of subcutaneous injection can effectively promote Plt recovery and reduce Plt transfusion with less adverse reactions, which is worthy of further application. Key words: Leukemia, acute; Thrombocytopenia; Interleukin-11