ALBERT

Description: Abstract 45 Background Homoharringtonine-based induction regimens have been widely used in China for patients with acute myeloid leukemia (AML), which have shown to improve the rate of complete remission (CR) and long-term survival. We aimed to further evaluate its efficacy and safety in treatment of de novo AML. Methods This phase 3 study was done in 17 institutions in China. Patients between the age of 14 and 59 with untreated AML were randomly assigned to receive HAA (homoharringtonine 2 mg/m2/day, days 1–7; cytarabine 100 mg/m2/day, days 1–7, aclarubicin 20 mg/day, days 1–7), HAD (homoharringtonine 2 mg/m2/day, days 1–7; cytarabine 100 mg/m2/day, days 1–7; daunorubicin 40 mg/m2/day, days 1–3) or DA (daunorubicin 40–45 mg/m2/day, days 1–3; cytarabine 100 mg/m2/day, days 1–7) regimen as induction therapy. Patients who achieved partial remission or had a decrease of blast ¡Ý60% could receive a same second induction course. All patients who had a complete remission were offered the same consolidation chemotherapy according to the cytogenetic-risk. The primary endpoints were CR and event-free survival (EFS). The trial is registered in Chinese Clinical Trial Register, number ChiCTR-TRC-06000054. Results 620 patients were randomly assigned to receive HAA (n=207), HAD (n=206) and DA (n=207) regimens. HAA or HAD regimen, as compared with DA regimen, resulted in a higher rate of CR in the first course of induction therapy (67.5% vs. 54.0%, P=0.005; 64.9% vs. 54.0%, P=0.026, respectively). The overall CR rate remained significantly higher in the HAA arm as compared with DA arm (75.0% vs. 61.9%, P=0.005). HAA or HAD regimen has similar rates of adverse events as compared with DA regimen, but was associated with significantly increased risk of induction death (5.8% vs. 1.0%, P=0.007; 6.6% vs. 1.0%, P=0.003, respectively). The EFS was greatly improved in the HAA arm (3-year EFS 35.4±3.5% vs.23.1±3.1%, P=0.002), while not significantly in the HAD arm (3-year EFS 32.7±3.5% vs.23.1±3.1%, P=0.078) as compared with the DA arm. Overall survival (OS) and relapse-free survival (RFS) did not differ significantly in the HAA or HAD arm as compared with DA arm, but an OS and RFS advantage of the HAA arm over the DA arm was observed in patients with favorable or intermediate cytogenetic profile (OS: P=0.014; RFS: P=0.022, respectively). Patients in the HAD arm with NPM1 but not FLT3ITD mutations, as compared with the patients in the DA arm, had an improved EFS (P=0.038). In intermediate cytogenetic profile, patients with mutant CEBPA had prolonged RFS in the HAA arm as compared with the DA arm (P=0.045). Conclusions Homoharringtonine-based induction regimens are associated with a higher rate of CR and improved survival as compared with DA regimen in AML. The toxicity is mild with the exception of a higher rate of induction death. Disclosures: No relevant conflicts of interest to declare.

Description: Imatinib (IM) is a higherly effective targeted drug for CML. However, some CML patients, especially accelerated and blast crisis phase, often relapse due to drug resistance resulting from the emergence of IM-resistant point mutations within the BCR-ABL tyrosine kinase domain. This stimulates the development of new kinase inhibitors that are able to override resistance to IM. HHGV678 is a novel tyrosine kinase inhibitor and we employed IM-sensitive (K562 and 32Dp210) and resistant (K562R and fifteen 32Dp210 mutants) BCR-ABL+ cell lines to compare HHGV678 with IM on growth inhibition. In addition, synergistic effect of HHGV678 with IM was observed in 32Dp210 and 5 BCR-ABL mutants frequently observed in CML patients. MTT assay results showed that the estimated IC50 value of HHGV678 for K562 and 32Dp210 were 15.5 and 28-fold, for K562R and 15 BCR-ABL mutants, were 1.4–124.0-fold lower than that of IM, indicating that HHGV678 was a more effective than IM against cell growth of IM-sensitive and resistant cells. Using combination index analysis, HHGV678 displayed synergistic growth inhibition when used with IM in BCR-ABL mutants (M244V, Q252H, Y253H, E255K and T315I). HHGV678, combined with IM at their IC50 concentration induced apoptosis 2–5 fold higher than that of HHGV678 alone in BCR-ABL mutants respectively, by annexin-V staining. At the same condition, HHGV6787 resulted in remarkable decrease in CrKL phosphorylation as determined by western blot. We conclude that HHGV678 have significant activity against IM-sensitive and resistant BCR-ABL+ cell, especially when it combined with IM that warrant further investigation in clinical trials.

Description: Acute myeloid leukemia (AML) is a malignant heterogeneous disease characterized by rapid clonal growth of myeloid lineage blood cells. This year there will be an estimated 20,830 new AML cases and an estimated 10,400 deaths from this deadly disease in the United States. Overall survival rates remain low despite advances in treatment with overall survival rates of 25% for adults and 65% for children. Resistance to frontline chemotherapy remains a major cause of treatment failure, highlighting the need for new therapies. Overexpression of the anti-apoptotic Bcl-2 family members is associated with chemoresistance in leukemic cell line models and with poor clinical outcome. Anti-apoptotic Bcl-2 family members, such as Bcl-2, Bcl-xL, and Mcl-1, sequester pro-apoptotic BH3-only proteins, such as Bim, which activate pro-apoptotic proteins Bax and Bak causing mitochondrial outer membrane permeabilization resulting in cytochrome c release and apoptosis. Thus, inhibition of anti-apoptotic Bcl-2 family members represents a promising approach for the treatment of AML. We previously demonstrated preclinical efficacy of a pan-Bcl-2 inhibitor, GX15-070, in combination with cytarabine in AML cell lines and primary patient samples. Another promising inhibitor, ABT-263, has shown preclinical efficacy, but has been associated with thrombocytopenia due to inhibition of Bcl-xL, thus much attention has been focused on inhibition of Bcl-2. ABT-199, a Bcl-2 selective inhibitor, has demonstrated encouraging results in AML, acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma, multiple myeloma, and breast cancer. We previously demonstrated that ABT-199 has a wide range of activity in AML cells (Niu X, et al. Leukemia. 2014; 28: 1557-1560.) However, it has limited efficacy in Bcl-xL and Mcl-1 dependent malignancies. Thus, intrinsic drug resistance remains a concern. Understanding the molecular mechanisms of resistance to ABT-199 will allow for rationally designed combination regimens to increase its antileukemic efficacy. In this study, we investigated the molecular mechanism underlying intrinsic resistance to ABT-199 in AML cells. Immunoprecipitation of Bim from ABT-199 treated cells demonstrated decreased association with Bcl-2, but increased association with Mcl-1, without corresponding change in mitochondrial outer membrane potential. ABT-199 treatment resulted in increased levels of Mcl-1 protein and unchanged or decreased Mcl-1 transcript levels. shRNA knockdown of Bim almost completely abolished ABT-199 treatment-induced increase of Mcl-1 protein levels, suggesting that the association with Bim plays an important role in stabilizing Mcl-1 protein. AML cells treated with ABT-199 in the presence of the protein translation inhibitor cycloheximide resulted in significantly longer Mcl-1 half-life and treatment with the proteasome inhibitor MG-132 resulted in increased Mcl-1 protein level and no further enhancement was detected when treated with combined MG-132 and ABT-199, suggesting that ABT-199 affects Mcl-1 protein stability. Combining conventional chemotherapeutic agent cytarabine or daunorubicin with ABT-199 resulted in increased DNA damage, decreased Mcl-1 protein levels, decreased association of Mcl-1 with Bim, and synergistic induction of cell death compared to ABT-199 alone, in both AML cell lines and primary patient samples obtained from AML patients at diagnosis independent of their sensitivities to ABT-199, thus providing evidence that screening for ABT-199 resistance is not necessary. Our results demonstrate that sequestration of Bim by Mcl-1 is a mechanism of intrinsic ABT-199 resistance, and this mechanism of resistance can be overcome by combining ABT-199 with daunorubicin or cytarabine in AML cells. Our findings, though in a limited number of primary patient samples, provide new insights into the mechanism of ABT-199 resistance in AML cells and support the clinical development of the combination of daunorubicin or cytarabine and ABT-199 in the treatment of AML. Disclosures No relevant conflicts of interest to declare.

Description: Background: Diseases whose treatment requires chronic transfusion therapy are relatively rare, and many have higher prevalence among certain ethnic groups and geographic regions. In these geographical regions, the patterns of care for these diseases and the epidemiology of iron overload (IOL) and other complications of treatment are currently undefined. To improve patient (pt) outcomes, it is important to understand how to diagnose, monitor, and manage these diseases. The TORS study aimed to collect information on a large number of newly diagnosed pts with various types of anemia and hemoglobinopathies to assess pt management considering diagnostic criteria and treatment pattern with iron chelation therapy (ICT) across various geographical regions. Methods: Inclusion and exclusion criteria were defined earlier by Siritanaratkul et al, EHA. 2015. Pts aged 〉2 years requiring chronic transfusion therapy with newly diagnosed anemias (

Description: Abstract 140 Background Arsenic trioxide increases the rate of complete remission (CR) and prolongs long-term overall survival in patients with acute promyelocytic leukemia (APL). We demonstrated that an oral arsenic-containing Realgar-Indigo naturalis formula (RIF) could yield clear synergistic effects in an in vivo murine APL model as well as an in vitro APL cell lines. The efficacy and safety of this formula were confirmed by a CR rate of 96.7% and reasonable safety profile in a multicenter Phase II clinical trial in China. To find out whether oral RIF could achieve similar remission and survival with ATO, the Chinese APL Cooperative Group conducted a phase 3 randomized study (APL07) that compared oral RIF with ATO in both the induction and maintenance therapies. Methods In this phase 3 randomized trial, 242 newly diagnosed APL patients were randomly assigned to receive oral RIF (n=121, daily 60 mg per kg body weight) or ATO (n=121, daily 0.15 mg per kg body weight) as a part of induction therapy. All patients also received all-trans-retinoic acid (ATRA; daily 25 mg per square meter) as induction therapy, and were between the ages of 15 and 60 years. After achieving CR, all patients were given three courses of consolidation chemotherapy with anthracycline and cytosine arabinoside. The maintenance treatment included eight cycles of sequential use of ATRA and RIF or ATO for two years. The primary endpoint was disease-free survival (DFS). The secondary endpoints were the rate of CR and overall survival (OS) and safety. Results At a median follow-up of 28 months, no significant differences were noted between RIF group and ATO group with respect to CR rate (99.1% vs.97.2%, P=0.62), DFS (98.9% vs.97.64%, P=0.6) (Figure 1A) and OS at 3 years (99.1% vs.96.6%, P=0.18) (Figure 1B). The rates of adverse events were similar in the two groups. The rate of treatment-related grade 3/4 liver toxic effects was 9.6% in the RIF group and 12.0% in the ATO group(p=0.67). When on the arsenic-containing treatment, the plasma arsenic content was higher in the ATO group than in the RIF group (56.3 vs. 23.6 μg/L, p=0.0002). The median levels of arsenics concentration of plasm, urine, hair and nail samples after completing therapy 12 months were below the lower limit of the normal control. Conclusions Oral Realgar-Indigo naturalis formula yielded a comparable high remission and long-term survival with arsenic trioxide as front-line treatment of newly diagnosed APL. Disclosures: No relevant conflicts of interest to declare.

Description: OBJECTIVES: Decitabine has been approved in China for treatment with high-risk Myelodysplastic syndromes (MDS) patients (pts) in 2008. However data of decitabine on efficacy and safety of low-dose decitabine in low- or intermediate 1-risk MDS was absence. Herein,3 years datas in our centre of low- or intermediate 1-risk MDS treated with decitabine were analysed to evaluate the efficacy and safety in two subgroups. METHODS: Inclusion Criteria:Patients of age 〉 18; Patients with low-or intermediate 1-risk MDS. The IPSS is used to classify patients with MDS across disease subgroups. ECOG performance status ≤ 2. And normal hepatic,renal and cardiac function. Study Design: Decitabine 20mg/m2 intravenously (IV) over the course of one hour daily for 3 days. Courses were repeated every 28 days when possible. Dose reductions for grade 3 and 4 toxicities were allowed for decitabine (to 10 mg/m2 or 15 mg/m2). The primary endpoint was overall response rate (ORR). RESULTS: In total, 37 patients were enrolled and treated from September 2014 to October 2017 in our center. The median follow-up was 26 months (range, 4-49 months). The median time from diagnosis to therapy with decitabine was 3 weeks (range, 1-52 weeks). Their F/M ratio was 16/21 and the median age of the enrolled population was 58 years (range, 40-71 years). More than 70% of patients had 2 to 3 cytopenias, and 43% were transfusion dependent at enrollment. Most patients had intermediate 1-risk MDS by IPSS (n=29). Next-generation sequencing was performed in 35 patients (90%). The most frequently detected mutations included TET2 (n=15; 41%), SF3B1 (n=7; 19%), ASXL1 (n=5, 13%), RUNX1 (n= 5, 13%), and SRSF2 (n=3, 8%). The ORR after 2 cycles of decitabine was 65% (24/37),with 35% of patients (13/35) achieving a CR. Hematologic improvement was seen in 19%(7/37). The median time to best response was 3 months (range, 1-12 months). The median number of cycles received was 5 (range, 1-13 cycles). 19% of patients (7/37) became transfusion independent. The EFS and OS were 68% and 78% respectively in 1 year. The treatment was well-tolerated, with most adverse events being of grade 1 to 2, Nausea (24%), Fatigue (14%), Infection/Neutropenic fever (19%), Constipation (6%), Diarrhea (6%). Grade 3 and higher nonhematologic adverse events were rare. Grade 3 adverse events were Infection/Neutropenic fever (6%), but rare, and no grade 4 adverse events were observed. CONCLUSIONS: These data confirm that decitabine is a feasible and effective agent for low- or intermediate 1-risk MDS pts, and its need longer time to response (more than 2 cycles). Safety profile was acceptable and the most adverse events were Nausea, Fatigue, and Infection/Neutropenic fever. Disclosures No relevant conflicts of interest to declare.

Description: BACKGROUND: BCR/ABL1 transcripts ≥ 10% after 3 months or 6 months was an effective prognosic indicator for long-term outcomes (Hanfstein B,et al. Leukemia,2012). The incidence of disease progression was significantly higher in patients who failed to achieve Early molecular response (EMR) rates-BCR/ABL1 transcripts ≥ 10% by 3 months or 6months (Hughes T,et al.Blood,2003).During 2009-2016,there have 429 patients (Pts) with standard dose Imatinib 400mg QD for first line in our centre,but 29.3% (102 Pts) BCR/ABL1 transcripts ≥ 10% after 3 months and 31.3% (77 Pts) BCR/ABL1 transcripts ≥ 1% after 6 months. OBJECTIVES: Here, 3 years datas from our centre of NIL 400mg BID (n=43) as secondline vs. high-dose IM 600mg QD (n=71) for standard-dose IM 400mg QD in newly dignosed CML-CP who failed to EMR were analysed to evaluate the molecular response rate and safety. METHODS: Inclusion Criteria:Patients of age ≥ 18,newly dignosed CML-CP (within 6 months of dignosis).BCR/ABL1 transcripts ≥ 10% at 3 or 6 months with standard dose IM 400mg QD. ECOG performance status ≥ 2. And normal hepatic,renal and cardiac function. Study Design: Datas of NIL 400mg BID (n=43) as secondline vs. high-dose IM 600mg QD (n=71) for standard-dose IM 400mg QD (n=114) in newly dignosed CML-CP who failed to EMR were analysed to evaluate by Sokal risk. Primary endpoints are cumulative incidence rates of MMR and rate of patients achieved MMR by Sokal risk. Secondary endpoints are OS and PFS by Sokal risk and safety. RESULT: Two study groups were balanced with age, gender and Sokal risk score (Table 1). Rates of cumulative incidence of MMR in two groups were 13.2% in NIL vs. 3.3% in IM respectively (P=.0010) at 3 months,34.3% vs. 14.8% respectively (P=.0042) at 6 months and 55.3% vs.34.4% respectively (P=.0143) at 12 months but there were not significantly different between two groups at 24 and 36 months (Figure 1). Rate of patient achieved MMR in study were 7.9% (n=3) in NIL vs. 4.9% (n=3) in IM respectively (P=.0087) at 3 months,15.8% (n=6) vs. 11.5% (n=7) respectively (P=.0076) at 6 months and 26.3% (n=10) vs. 14.8% (n=9) respectively (P=.0084) at 12 months in low risk group by Sokal risk score; 10.5% (n=4) vs. 6.6% (n=4) respectively (P=.0009) at 6 months and 21.2% (n=8) vs. 13.1% (n=8) respectively (P=.0041) at 12 months in intermediate risk group (Figure 2). PFS of two groups were 80.3% vs. 70.2% respectively in low risk (P=.0013) and 78.6% vs. 66.8% respectively in intermediate risk (P=.0051) at 60 months but there were not significantly different in high risk (Figure 5,6). The OS of two groups were not significantly different in all Sokal risk at 12,36 and 60 months also (Figure 3,4). The most common (rate of AEs ≥ 10%) hematologic AEs were grade 1/2 in two groups but AEs rate of NIL was less than IM.Nonhematologic AEs also focused on grade 1/2, included rash (28.9%,n=11) and myalgia (13.2%,n=5) in NIL; oedema (41.0%,n=25) and nausea & vomiting (34.4%,n=21) in IM commonly, but there were not significantly different between two groups. Grade 3/4 AEs were uncommon in hematology & nonhematology (Table 2). CONCLUSION: NIL resulted more rapidly to achieve MMR compared with high dose IM who failed to EMR with standard dose IM. Low ang Intermediate groups of Sokal risk achieved significantly higher MMR rate at 6 and 12 months and higher PFS at 60 months in patients receiveing NIL compared with IM but OS similarly in all groups. The safety profiles of NIL and IM were different and the hematologic AEs of NIL was less than IM. The result of this study support that NIL can achieve molecular response rapidly for BCR/ABL1 transcripts ≥ 10% with Imatinib (IM) 3 or 6 months in CML-CP. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Description: Background: Previously, real-world baseline characteristics and response monitoring pattern of Chinese CML patients treated with dasatinib were poorly studied and rarely reported. The Chinese dasatinib registry CA180-518 is a multicenter, observational study that provides us with a unique opportunity to obtain such information. Here we reported baseline characteristics and monitoring adherence of patients enrolled in this study. Methods: Imatinib-resistant/-intolerant CML adult patients in any phase, who planned to receive or were receiving dasatinib therapy based on physician's clinical judgement, were enrolled in this study and were separated into 3 cohorts based on their disease phases: chronic phase (CP), accelerated phase (AP) and blast phase (BP). Patients were to be followed until death, withdrawal of consent, end of study or loss of follow-up. Patient visit schedule, evaluation and treatment decision were determined solely by the physician in their real-world clinical practice. The first and the second patient visits were designed at Month 0 and Month 3. Results: From April 2013 to June 2015, a total number of 126 patients from hematology division of 28 hospitals in China were enrolled. Of these, 116 were included in the full analysis set (FAS), including 69 patients with CML-CP, 22 patients with CML-AP and 25 patients with CML-BP. Patients in the FAS had a median age of 43 years. 60.34% (70/116) were male. ECOG performance status (PS) at diagnosis was available for 81.90% (21/116) patients and most of them (75.00%, 87/116) had a good PS (PS0-PS1). Median disease duration was 33.00 months (Q1-Q3:14.00-71.50). 37.38% (40/116) of the patients had received imatinib treatment for ≥ 24 months. 75% (87/116) of the patients used dasatinib due to primary or secondary imatinib resistance and 25% (29/116) due to imatinib intolerance. 69 of 116 patients had undergone genetic mutation test at baseline, among which, 76.80% (53/69) were detected with genetic mutations. Y253F/H (15.94%; 11/69), E255K/V (11.59%; 8/69) and F359V/I (10.14%; 7/69) were the three most common mutation types, which also happened to be the mutations associated with nilotinib-resistance. 18.97% (22/116) patients had baseline comorbidities and 50% (11/22) of them had ≥2 comorbidities. The most common comorbidity was cardiovascular diseases (CVD)/metabolic syndrome (MS) (54.54%, 12/22). It is also important to note that 22.72% (5/22) patients had a history of hepatitis B virus (HBV) infection. For 62 CML-CP patients who completed the second visit, 64.52% (40/62) had taken routine blood test, 72.58% (45/62) had taken PCR test and 22.58% (14/62) had taken cytogenetic test. It is noteworthy that there were still 19.35% (12/62) patients who took none of the laboratory tests mentioned above. The efficacy of dasatinib is being assessed based on the test results and will be reported in the further. Conclusion: The results from this analysis provided real-world data about baseline characteristics and response monitoring pattern of Chinese CML patients treated with dasatinib. Although less than 20% patients had baseline comorbidities, the fact that the most common comorbidity was CVD/MS should raise awareness, because TKI-related vascular AEs (VAEs) may develop preferentially in patients with these preexisting risk factors. Although the frequency of VAEs is lower in patients receiving dasatinib compared with nilotinib or ponatinib, for these patients, it is still important to closely monitor metabolic and cardiovascular parameters during the follow-up to reduce the vascular risk. Meanwhile, for patients who are carriers of HBV, EMA recently recommended that signs and symptoms of active HBV infection should be closely monitored throughout therapy and for several months following termination of therapy, given the risk of HBV reactivation for all TKIs. Besides, patient adherence to monitoring is a concerning problem for CML management in China. This data indicates a considerable amount of CML patients, who do not follow current recommended guidelines on response monitoring. Acknowledgment: BMS funded this research and medical writing support Disclosures No relevant conflicts of interest to declare.

Description: BACKGROUND: Pegylated liposomal doxorubicin (CAELYX®) is a liposomal formulation of doxorubicin sterically stabilized by the grafting of segments of polyethylene glycol (PEG) onto the liposomal surface. Given the demonstrated efficacy of VAD (vincristine and doxorubicin and oral dexamethasone) in Multiple Myeloma (MM) patients and the potential for CAELYX® to extend the duration of bone marrow exposure to therapeutic levels of doxorubicin, a combination regimen of CAELYX®, vincristine, and reduced-dose dexamethasone (DVD) has been actively investigated in MM patients. Studies showed that substituting CAELYX® for doxorubicin in the VAD regimen and reducing the dose of dexamethasone in MM patients improves the safety profile and convenience of the treatment regimen without compromising efficacy. Due to potential differences in metabolism of these patients, safety and efficacy results may vary. Thus, we carried out this study in 82 newly diagnosed MM patients in China, in order to demonstrate the efficacy and safety profiles of DVD. METHODS: Patients (n=82) from 15 sites were recruited in this study. CAELYX® (40mg/m2) was infused intravenously over 60-minutes, administered every 28 days. Vincristine (2.0mg) was administered intravenously on Day 1 of each cycle. Dexamethasone (40 mg) was administered from Day 1- Day 4 of each cycle orally or intravenously. The treatment was repeated every 28 days for 4 cycles. RESULTS: Upon ITT analysis, the overall response rate was approximately 68% (56/82); 11% of the patients achieved complete remission (CR), 40% achieved partial response (PR), 17% achieved minimal response; 15% had stable disease (SD), and 12% o had progressive disease (PD) after the treatment. The cumulative 4-month progression-free survival (PFS) was 88%. The incidence of all the adverse events was 46%. The most common non-hematological toxicities were palmar-plantar erythrodysesthesia (13.4%) and stomatitis (6.1%), respectively. CONCLUSION: Pegylated liposomal doxorubicin, vincristine and reduced dose dexamethasone combination (DVD) regimen is an effective and safe regimen in newly diagnosed multiple myeloma patients in Chinese population.

Description: Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by transient or persistent decrease of platelet count. ITP is the most common cause of thrombocytopenia in early pregnancy. Patients with severe thrombocytopenia (platelet count 〈 20 ×109/L) are at risk of spontaneous bleeding, postpartum hemorrhage and placental abruption. The aim of this study is to determine the efficacy and the safety of recombinant human thrombopoietin (rhTPO) in the management of ITP in pregnancy. This study is registered at www.clinicaltrials.gov as NCT02391272. Patients at eight centers in China were enrolled. Enrollment criteria were pregnant women aged between 18 and 50, who failed to respond to first-line treatments of ITP and/or were refractory to platelet transfusion. Patients' platelet counts were below 30×109/L with bleeding manifestations. Gestational age of the patients was over 12 weeks. Informed consent was obtained from each patient in accordance with the Declaration of Helsinki. Thirty-one patients were enrolled into the study. The median age of the pregnant ITP patients was 26 years (range 19 - 39 years) and 90.6% (29/31) were primigravidae. The median gestational age was 24 weeks (12 - 38 weeks). The median baseline platelet count was 10×109/L (range 1 - 29×109/L). 74.2% (23/31) of these patients were diagnosed as ITP before pregnancy and 25.8 % (8/31) during pregnancy. All eligible participants received rhTPO at an initial dose of 300U/kg once daily subcutaneously for 14 days, 74.2% (23/31) of these patients responded to the initial 14-day rhTPO therapy, including 10 CR and 13 R. Eight patients were NR though their platelet counts rose mildly. The median platelet count of responder was 100×109/L (range from 30 to 250×109/L) at day 14. Then the responders received sequential maintenance therapy through the end of week 12 after delivery. To reduce the risk of thrombocytosis during maintenance, dose was tapered to 300U/kg every other day when platelet counts exceeded 50 ×109/L and treatment stopped when platelet counts above 100×109/L. Only one responder had a transient loss of response due to influenza. After dose adjustment of rhTPO from 300U/kg every other day to 300U/kg every day, the platelet count exceeded 50×109/L in the next visit. The platelet counts gradually dropped after withdrawal of rhTPO. The relapse free survival (platelet count at least 30×109/L) at week 4 and week 12 after withdrawal of rhTPO was 69.6%(16/23) and 21.7%(5/23), respectively (Figure 1). Safety and adverse events were evaluated in all 31 participants. rhTPO was well tolerated. Only mild previously reported adverse events were observed, including one case of dizziness, one of fatigue and one of pain at injection site. There were no new reported adverse events during the observation period and no adverse event-related study withdrawals. In all the 31 newborns, the median age of gestation was 39 weeks (range 36-40, 3 cases had age of gestation〈 37 weeks); median birth weight was 3.1 kg (range 2.3-4.2kg, 2 had birth weight