Difference In Overall Response Rate Research Articles

Real life clinical outcomes of relapsed/refractory diffuse large B cell lymphoma in the rituximab era: The STRIDER study.

Relapse and refractory (R/R) rates after first-line R-CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively. We conducted a retrospective real-world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients. Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed. At a median follow up of 50 months, 5-year overall survival from diagnosis (OS-1) was 66.5%, and 2-year progression free survival (PFS-1) was 68%. 134 (34.4%) patients relapsed (n = 46, 11.8%) or were refractory (n = 88, 22.6%) to R-CHOP. Most employed salvage treatments included platinum salt-based regimens in 38/134 (28.4%), lenalidomide in 14 (10.4%). Median OS and PFS after disease relapse or progression (OS-2 and PFS-2) were 6.7 and 5.1 months respectively. No significant difference in overall response rate, OS-2 or PFS-2 in patients treated with platinum-based regimens versus other regimens was observed. By multivariate analysis, age between 60 and 80 years, germinal center B cell type cell of origin and extranodal involvement of <2 sites were associated with better OS-2. Our findings confirm very poor outcomes of R/R DLBCL in the rituximab era. Widespread approval by national Medicine Agencies of novel treatments such as CAR-T cells and bispecific antibodies as second-line is eagerly awaited to improve these outcomes.

Efficacy of acupoint injection in the treatment of chronic eczema and its influence on peripheral blood T cells.

Chronic eczema significantly impacts daily life, social interactions, and quality of life; however, no curative treatment has been identified. To determine the clinical efficacy of acupoint injection for chronic eczema and its influence on peripheral blood T cells. Eighty patients with chronic eczema treated at our hospital between June 2022 and March 2023 were randomly assigned to a control group (n = 40), which received conventional Western medicine treatment, or an observation group (n = 40), which received routine Western medicine treatment plus acupoint injection of triamcinolone acetonide. Response and adverse reaction rates, as well as differences in the levels of serum cytokines IFN-γ, IL-2, IL-4, and IL-10 before and after treatment were investigated. No difference in overall response rates were found between the observation and control groups (100% vs 90%, respectively; P > 0.05); however, the observation group had a higher marked response rate than the control group (87.5% vs 52.5%; P < 0.05). Both groups had decreased Eczema Area and Severity Index scores and increased pruritus after treatment (P < 0.05), particularly in the observation group (P < 0.05). The observation group had an adverse reaction rate of 2.5% (1/40), which did not differ significantly from that of the control group (P > 0.05). The observation group exhibited higher post-treatment INF-γ and IL-2 but lower IL-4 levels than the control group (P < 0.05); however, no significant inter-group difference was observed in post-treatment IL-10 levels (P > 0.05). Acupoint injection of triamcinolone acetonide is safe and effective in treating chronic eczema. Its therapeutic mechanism is related to the regulation of peripheral blood T cell levels, inhibition of inflammatory reactions, and mitigation of immune imbalance.

Carfilzomib plus rituximab, ifosfamide, carboplatin and etoposide (C-RICE) led to higher response, OS, and PFS in patients with transplant-eligible relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

7042 Background: The CORAL study highlighted the need to develop novel salvage regimens for R/Rr/r DLBCL previously treated with R+CHOP. Overall response rate (ORR) to second line immuno-chemotherapy was 51% with a 3-year progression free survival (PFS) of 30% following high-dose chemotherapy and autologous stem cell support (HDC-ASCS). Optimal disease control (complete remission [CR] or partial remission [PR]) prior to HDC-ADCS and more recently to chimeric antigen receptor T-cell therapy (CAR T), correlates with improved outcomes. Dysregulation of Bcl-2 family members has been associated with acquired resistance to rituximab and chemotherapy which we have previously shown may be mitigated by co-treatment with proteasome inhibition in pre-clinical model. Subsequently, we conducted a Phase I/II clinical trial evaluating the safety and efficacy of CRICE as salvage therapy for R/R DLBCL (Blood Adv. 2023 7:1146-1155). Methods: Here we retrospectively compared the clinical outcomes of R/R DLBCL patients treated with CRICE (N=28) versus RICE (N=38) on our prior clinical trial (NCT01959698). Demographic, clinical, and pathological characteristics were collected for both groups (Table). Study endpoints consisted of differences in overall response rate (ORR), CR/PR rates, median progression free survival (PFS) and overall survival (OS) between the two cohorts. Results: The addition of Carfilzomib to RICE resulted in improved clinical outcomes. A higher ORR (92.9 vs 76.3, P=0.073) and CR rates (82.1 vs. 44.7, P=0.002) were observed in CRICE vs. RICE treated patients. Multivariate analysis confirmed the higher CR rates in CRICE vs. RICE when adjusted by DLBCL subtype (GCB vs. nNon-GCB, P=0.003). More CRICE patients proceeded to HDC-ASCS (52.6% vs. 47.4%, P=0.618). The 3yr PFS rate was higher in CRICE (54%, 32-72%) vs. RICE treated patients (35%, 19-51%). While the median PFS was longer in CRICE treated patients 36.8m (0.8, 73.2) vs. 3.2m (0.5, 54.2) (RICE), it did not reach statistical significance (P=0.714). No differences in OS were observed between CRICE &amp; RICE patients, median OS 67.3m vs. 71.8m. Conclusions: The CRICE outcomes were more striking in patients with non-GCB r/r DLBCL (ORR 85%, mPFS and OS not reached). CRICE led to high CR rates and longer PFS among r/r DLBCL patients, especially in non-GCB DLBCL patients. CRICE could be an attractive regimen to achieve disease control in r/r DLBCL patients undergoing consolidation therapy with HDC-ASCT or CAR T-cell therapy. [Table: see text]

Surrogate endpoints for overall survival in advanced hepatocellular carcinoma: A meta-analysis.

563 Background: Recent advances in systemic therapies have resulted in improved overall survivals (OS) for patients with advanced hepatocellular carcinoma (aHCC). The most commonly utilized primary endpoint for phase III trials in aHCC is OS. A robust surrogate endpoint (SEP) can reduce time and financial costs of future trials and accelerate regulatory approvals of new therapies. We conducted a literature-based meta-analysis to evaluate SEPs for OS in aHCC. Methods: Randomized controlled trials evaluating systemic therapies in aHCC published 2007 - 2023 were identified through a systemic literature search of Cochrane and Medline databases as well as of abstracts presented at ASCO and ESMO meetings. Hazard ratios (HR) for OS and progression-free survival (PFS) and time to progression (TTP) were extracted. ΔORR was calculated as the difference in overall response rates (ORR) between control and experimental arms. Pearson correlation and mixed-effects meta-regression analyses were performed. Surrogate threshold effect (STE) was determined for each comparison when possible. A p &lt; 0.05 was considered to be statistically significant. Results: 26 trials were identified in the first-line setting with 14,827 patients and 11 trials in the subsequent-line setting with 5,316 patients. In first-line trials, immunotherapy (IO) is associated with higher ORR than other agents (p=0.003). There are statistically significant correlations between HRs of PFS/TTP/ΔORR and OS (Table). The relationship between HR-PFS and HR-OS persists in trials with or without IO, but only in trials enrolling &lt; 30% patients of non-viral aetiologies. In subsequent-line trials, there are statistically significant correlations between HRs of PFS/TTP and OS (Table). STE for HR PFS is 0.68 and 0.87 respectively for 1st and subsequent line trials. Conclusions: There are moderate to strong correlations between PFS and OS in aHCC in first-line and subsequent line trials. STE for HR-PFS of 0.68 in first-line and 0.87 in subsequent-line settings can guide sample size calculation in future clinical trials. [Table: see text]

Chronomodulated chemotherapy for locoregionally advanced nasopharyngeal carcinoma: A phase II randomized controlled trial

ObjectiveTo validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC). MethodsParticipants for this phase II randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University. Patients enrolled (128 in total, 112 in the final analysis) between April 1, 2017, and February 28, 2018, were randomly divided into the chronochemotherapy and conventional chemotherapy groups. In the chronochemotherapy group, docetaxel was intravenously administered between 3:30 a.m. and 4:30 a.m. on day 1, followed by intravenous administration of cisplatin between 10:00 a.m. and 10:00 p.m. from day 1to day 5. In addition, 5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m. and 10:00 a.m. (2nd day) from day 1 to day 5. In the conventional chemotherapy group, docetaxel (on day 1), cisplatin (on day 2), and 5-fluorouracil (from day 1 to day 5, 120 ​h in total) were administered without time-specific constraints. Both groups underwent intensity-modulated radiation therapy with 6-MV X-rays. The gross target volume (GTV) comprised the nasopharyngeal GTV and cervical lymph node GTV. The primary endpoint was immune function, quantified by measuring dendritic cell and lymphocyte subsets, whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events. Pearson Chi-square test was applied to compare total events between the groups, Mann-Whitney U test was used to compare the DC subsets and toxicities, and Wilcoxon signed-rank test ​was used to compare the continuous variables between the two groups. ResultsChronochemotherapy preserved immune function, as evidenced by elevated levels of myeloid dendritic cells (P ​= ​0.394) and higher CD4/CD8 ratio (P ​= ​0.781). No significant difference in overall response rate, measured as the sum of complete and partial response rates, was observed between the groups (P ​= ​0.711). A reduction in the incidence of vomiting (P ​= ​0.002), stomatitis (P ​= ​0.028), and mucositis (P ​= ​0.028) was observed in the chronochemotherapy group. Leukopenia incidence rate was 83.3 ​% and 92.3 ​% in the chronochemotherapy and conventional chemotherapy groups, respectively (P ​= ​0.232). ConclusionsIn patients with locoregionally advanced NPC, the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy; however, chronochemotherapy shows fewer adverse events.

Bridging therapy with axicabtagene ciloleucel for large B-cell lymphoma: results from the US Lymphoma CAR-T Consortium

AbstractDuring the manufacturing period of autologous chimeric antigen receptor (CAR) T-cell therapy, patients may experience a decline in their condition due to cancer progression. In this study, we investigated the impact of bridging therapy (BT) on the outcome of patients with relapsed/refractory large B-cell lymphoma who received antilymphoma treatment between leukapheresis and axicabtagene ciloleucel (axi-cel) infusion. We conducted our analysis using data from the multicenter US Lymphoma CAR-T Consortium, with a median follow-up of 33 months (range, 4.3-42.1). Out of the 298 patients who underwent leukapheresis, 275 patients received axi-cel. A total 52% of patients (n = 143) who received BT had a higher baseline risk profile than patients who did not receive BT, and these patients, as a group, had inferior outcomes compared with those who did not receive BT. However, after propensity score matching between the 2 groups, there were no statistically significant differences in overall response rate (77% vs 87%; P = .13), complete response rate (58% vs 70%; P = .1), progression-free survival (hazard ratio [HR], 1.25; P = .23), and overall survival (HR, 1.39; P=.09) between the BT group and the no-BT group, respectively. Analyzing the effects of BT in the whole cohort that underwent leukapheresis regardless of receiving axi-cel (intention-to-treat analysis) showed similar results. Radiation BT resulted in outcomes similar to those observed with nonradiation BT. Our findings suggest that BT may be safe without a significant impact on long-term survival for patients who require disease stabilization during the manufacturing period. Moreover, our results suggest that there is no clear advantage to using radiation-based BT over nonradiation-based BT.

Efficacy of Bispecific Antibodies Vs CAR-T in the Treatment of Extramedullary Disease and High-Risk Cytogenetics in Relapsed Multiple Myeloma: A Systematic Review and Meta-Analysis

Background: Bispecific antibodies (BsAb) and Chimeric antigen receptor T-cell therapy (CAR-T) have emerged as a promising treatment option for patients with relapsed, refractory multiple myeloma (RRMM) for greater than four previous lines of therapy. The efficacy of these novel drugs in extramedullary disease (EMD) and high-risk cytogenetic abnormalities (HRCA) is relatively less reported. The purpose of this systematic review and meta-analysis is to compare the efficacy of BsAbs vs CAR-T in the treatment of EMD and HRCAs in RRMM. Methods: A systematic literature search was conducted to identify clinical trials that investigated BsAbs and CAR-T therapies in treating RRMM patients using the PubMed, Cochrane, ASH 2022 and ASCO 2023 abstracts using search terms (bispecific antibodies) AND (multiple myeloma), (CAR T cell therapy) AND (multiple myeloma). For BsAbs, our search on PubMed yielded 263 studies. 7 were clinical trials and 5 of these were included. 6 ASH abstracts and one ASCO abstract were also included resulting in a total of 12 studies considered for this meta-analysis. For CAR-T, our search on PubMed and COCHRANE yielded 84 and 20 studies respectively. After screening, we have included 21 studies and 6 ASCO abstracts in final analysis. RStudio Desktop Version 2023.03.0+ 386 was used for statistical analysis. Cochrane-Q test and I² statistic were used to assess the statistical heterogenicity. Fixed effect model was used for low statistical heterogeneity (P &amp;gt; 0.05 in Cochrane-Q test and I² &amp;lt; 50%), while a random effect model was used for high statistical heterogeneity (P &amp;lt; 0.05 in Cochrane-Q test and I² &amp;gt; 50%). Categorical outcomes were summarized by pooled proportion with 95% CI. Subgroup analysis was performed wherever required. P &amp;lt;0.05 was considered statistically significant. Results Bispecific antibodies Overall response rates (ORR) were reported in a study population of 823 patients across 12 studies. The ORR was reported in 4 studies (n=106) for EMD and 4 studies (n=100) for HRCA respectively. The pooled ORR was 0.67 [95% CI; 0.59; 0.76) for the whole group. The pooled ORR was 0.48 (95% CI of 0.31 to 0.65) for EMD and 0.60 (95% CI of 0.51 to 0.70) for HRCA respectively. Subgroup analysis showed that there was a statistically significant difference in overall response rate according to different targets. However, there was no statistically significant difference in the ORR between the drugs with respect to EMD and HRCA. Combination therapy of Teclistamab and Talquetamab has highest ORR and RR in EMD disease compared to other BsABs in a study by Cohen et al. Funnel plot is symmetrical and showed no probability of publication bias for overall response rate for bispecific antibodies with a p-value of 0.676. CAR T cell therapy ORR with CAR-T cell therapy was reported across 27 studies with pooled sample size of 1469. The ORR was reported in 14 studies (n=172) for EMD and 11 studies (n=268) for HRCAs, respectively. The pooled ORR was 0.86 (95% CI of 0.82 to 0.90). The pooled proportion of RR among MM patients with EMD and HRCAs was 0.77 (95% CI of 0.68 to 0.87) and 0.77 (95% CI of 0.69 to 0.86), respectively. Funnel plot asymmetry showed possible publication bias for overall response rate for CAR T cell therapy with p-value of 0.021. Bispecific antibodies vs CAR-T. ORR in the whole cohort (P &amp;lt;0.001), EMD cohort (P &amp;lt;0.001), and HRCA cohort (P &amp;lt;0.046) were found to be significantly higher in CAR-T cell therapy as compared to bispecific antibodies. Conclusion: BsABs and CAR-T cell therapy are effective treatment options for relapsed MM patients.ORR in the whole cohort, EMD cohort, and HRCA cohort were found to be superior with CAR T cell therapy. However, it is difficult to make direct comparisons of pooled estimates of two different therapies. There was no significant difference in EMD and HRCA between the different types of BsAb therapy. Better reporting of EMD responses is urgently needed in published clinical data to know the true effect size and develop strategies to overcome this.

Impact of 1q21 Gain and Amplification on Daratumumab-Treated Multiple Myeloma Patients: Real-World Data from the Australia-New Zealand and Asia-Pacific Myeloma and Related Diseases Registries

Introduction: Gain/amplification of 1q21 (1q21+) is found in 40% of patients (pts) with newly diagnosed Multiple Myeloma (MM). There is increasing evidence that presence of gain of 1q21 [gain(1q21), 3 copies] or amplification of 1q21 [amp(1q21), ≥4 copies] are independent poor prognostic factors. A recent post-hoc analysis of the ICARIA-MM and IKEMA studies showed that the addition of monoclonal anti-CD38 antibody isatuximab in combination with pomalidomide-dexamethasone or carfilzomib-dexamethasone abrogated the negative impact of 1q21 on progression-free survival (PFS). However, the impact of 1q21+ has not been consistently assessed in daratumumab (Dara) exposed pts. Methods: We identified MM pts treated with Dara between Jan 2020 and Jan 2023 from the Australia-New Zealand and Asia-Pacific Myeloma and Related Diseases Registries. Pts who had interphase fluorescence in situ hybridization (FISH) testing were included. High-risk cytogenetics (HRCyto) was defined as the presence of t(4;14), t(14;16) or del(17p) by FISH, and standard risk cytogenetics (SRCyto) as pts without 1q21+ and HRCyto. Pt groups analysed were: (1) without 1q21+ vs with 1q21+ (2) SRCyto vs isolated 1q21+ vs HRCyto without 1q21+ vs HRCyto with 1q21+. Subgroup analyses performed include: (3) gain(1q21) vs amp(1q21). Overall survival (OS) and PFS from commencement of Dara were estimated using the Kaplan-Meier method. Comparisons of PFS and OS were performed using the log-rank test. Categorical data were compared using a chi-square test and continuous variables with a rank-sum test. Results: Of 654 pts who received Dara, 451 had interphase FISH testing performed and were included. There were 132 pts with 1q21+ [gain(1q): 23, amp(1q):14, gain/amp status unknown: 95] and 319 without. Median follow up was 15 months (95% CI 14-18). Median prior lines of therapy was 1 (IQR 1-2). Dara-based regimens used were: Dara monotherapy (17.7%), Dara-bortezomib-dex (54.6%), Dara-lenalidomide-dex (11.3%), Dara-pomalidomide-dex (DPd) (9.3%), Dara-carfilzomib-dex (DKd) (2.5%) and Dara-bortezomib-lenalidomide-dex (4.6%). There were no differences in age, gender, ECOG, line of therapy in which Dara was used, or rate of autologous stem cell transplantation between pts with 1q+ vs pts without (Table 1). Pts with 1q21+ had higher rates of other HRCyto (37.1% vs 20.4%; p=0.005) and ISS Stage 3 disease (44.1% vs 29.3%; p=0.005) vs those without 1q21+. There was no significant difference in overall response rate (65.9% vs 71.6%; p=0.32). Through univariate analyses, PFS for 1q21+ pts was significantly shorter than those without 1q21+ [median PFS 8.2 vs 18.4 months (HR 1.7, 95% CI 1.3-2.3; p&amp;lt;0.001)] (Figure 1). This difference was still significant when adjusted for ISS, the presence of other HRCyto and country of treatment (HR 1.61, 95% CI 1.17-2.22; p=0.004). Pts with 1q21+ with or without HRCyto, and those with HRCyto and no 1q21+ had inferior PFS vs SRCtyo (median PFS 7.7 vs 8.9 vs 8.5 vs 30.3 months; p&amp;lt;0.001) (Figure 2). Of the pts where 1q21+ copy number was available, OS was significantly poorer in pts with amp(1q) vs those with gain(1q) (median OS 22.6 vs 46.9 months; p=0.035). There was also a trend towards poorer PFS in pts with amp(1q) (median PFS 4.9 vs 10.5 months; p=0.096) Conclusions: 1q21+ often co-exists with other HRCyto abnormalities. However, it remains an independent negative prognostic marker. The use of Dara does not appear to abrogate the negative impact of 1q21+ on PFS. Amp(1q21) potentially confers an even poorer outcome. This finding differs from an earlier retrospective study (Parrondo et al, Blood 2022), although &amp;lt;10% of patients in our study received DKd and DPd combinations. As such, more data on Dara in combination with carfilzomib and pomalidomide is needed.

Randomized Controlled Trial of Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy Versus Long-Course Chemoradiotherapy in Locally Advanced Rectal Cancer: Comparison of Overall Response Rates.

Management of locally advanced rectal cancer (LARC) is evolving with current emphasis on the addition of chemotherapy to short course radiotherapy (SCRT). We primarily aimed to analyse the difference in overall response rates between SCRT with sequential chemotherapy and standard long-course chemoradiotherapy (LCCRT)in LARC. After randomization, patients in arm A received 45Gy in 25 fractions over 5weeks with concurrent capecitabine while patients in arm B received 25Gy in 5 fractions over 1week followed by 3 cycles of CAPOX (capecitabine and oxaliplatin) chemotherapy. Clinical and radiological response assessment was made after the completion of neoadjuvant treatment, a week prior to surgery. Adjuvant chemotherapy was added to complete 6months of peri-operative chemotherapy. Surgery was performed between 8 and 10weeks of completion of radiation treatment in both arms. Of the 33 patients recruited in this study between February 2020 to July 2021, 17 patients were randomized to arm A and 16 to arm B. The rates of complete tumour regression were 23.1% in arm A versus 35.7% in arm B (p-value = 0.683). Pathological complete response (pCR) rate was 20% arm A versus 30% in arm B (0.446). A higher number of patients in arm B experienced grade 3 diarrhoea, whereas acute skin toxicity was seen only in arm A. SCRT had fewer treatment interruptions compared to LCCRT. SCRT followed by three cycles of CAPOX chemotherapy in the neoadjuvant setting is comparable to LCCRT in terms of tumour response. This may be a better alternative regimen with fewer treatment interruptions in a resource-limited setting.

Clinical characteristics and outcome of patients with combined hepatocellular-cholangiocarcinoma—a European multicenter cohort

There is no clear consensus on the optimal systemic treatment regimen in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients. We describe clinical characteristics and outcome of cHCC-CCA patients, with a special focus on patients receiving palliative systemic therapy, including immune checkpoint inhibitors (ICIs). In this European retrospective, multicenter study, patients with histologically proven cHCC-CCA treated at four institutions between April 2003 and June 2022 were included. In patients receiving palliative systemic therapy, outcome was compared between cytotoxic chemotherapy (CHT)- and non-cytotoxic CHT (nCHT)-treated patients. Of 101 patients, the majority were male (n= 70, 69%) with a mean age of 64.6 ± 10.6 years. Only type of first-line treatment was independently associated with overall survival (OS). Palliative systemic therapy was administered to 44 (44%) patients. Of those, 25 (57%) patients received CHT and 19 (43%) had nCHT (n= 16 of them sorafenib) in systemic first line. Although there was no significant difference in overall response rate (ORR; CHT versus nCHT: 8% versus 5%), disease control rate (24% versus 21%), and median progression-free survival {3.0 months [95% confidence interval (CI) 1.4-4.6 months] versus 3.2 months (95% CI 2.8-3.6 months), P= 0.725}, there was a trend towards longer median OS in the CHT group [15.5 months (95% CI 8.0-23.0 months) versus 5.3 months (95% CI 0-12.5 months), P= 0.052]. However, in multivariable analysis, type of first-line regimen (CHT versus sorafenib) was not associated with OS. ORR in patients receiving ICIs (n= 7) was 29%. In patients with cHCC-CCA, OS, progression-free survival, ORR, and disease control rate were not significantly different between individuals receiving CHT and patients receiving nCHT. Immunotherapy may be effective in a subset of patients. Prospective studies are needed to identify optimal systemic treatment regimens in cHCC-CCA.

Outcomes of Older Patients with Aplastic Anemia Treated with Frontline Anti-Thymocyte Globulin (ATG)-Based Immunosuppressive Therapy

Background: Advances in the treatment of aplastic anemia (AA), such as the addition of eltrombopag (EPaG) to immunosuppressive therapy (IST) and the expanded use of unrelated and haploidentical stem cell transplant (SCT) have steadily improved outcomes. However, little is known about the characteristics and outcomes of patients (pts) ≥ 60 years (yrs) of age with newly diagnosed AA who have been treated with an ATG-based regimen. Presumed low bone marrow (BM) reserves, higher frequency of underlying clonal hematopoiesis, intolerance to therapy, comorbidities, and challenges in proceeding to salvage SCT have led to the speculation that response and survival of these pts to IST may be inferior than their younger counterparts. Methods: We retrospectively analyzed the characteristics and outcomes of pts ≥ 60 yrs of age (OLDER) at the time of diagnosis of AA treated with frontline (F/L) ATG based therapy at our center and compared them to pts < 60 yrs of age (YOUNG) treated with F/L ATG over the same time period. We captured their clinical characteristics, cytogenetic abnormalities, mutations in DNMT3A (D), ASXL1 (A) and TET2 (T), exposure to EPaG, response, time to response (TTR) and survival. Overall response included complete and partial response per the standard definitions. Relapse free survival (RFS) was tabulated from the time of best response to loss of response, 2nd ATG infusion, salvage SCT or death (whichever was earlier) and overall survival was tabulated from the time of response to death from any cause. Results: From Jan 2011-May 2012, 43 OLDER pts were treated as F/L for AA of whom 41 (95%) received ATG based therapy; 68 YOUNG pts were treated as F/L for AA over the same time period of whom 62 (91%) received ATG based regimen. Four YOUNG pts vs. no pts in the OLDER group received upfront SCT, and 2 pts in each group were treated with non ATG based therapy: single agent CSA, EPaG, or alemtuzumab. Comparative baseline characteristics are depicted in Table 1. There were no differences in the baseline WBC, peripheral blood lymphocyte percentage and platelet counts between the ATG treated OLDER and YOUNG groups. Both groups had similar frequencies of cytogenetic abnormalities and PNH clones, though OLDER pts had mutations in D-A-T genes compared to the YOUNG group (62% vs. 38%, p=0.05). Both groups had equal concurrent exposure to EPaG with ATG. Cumulatively 23/41 (56%) pts in the OLDER group had an overall response (OR) compared to 43/62 (70%) pts in the YOUNG group (p=0.1); 11/23 (48%) and 23/43 (53%) responders in each group attained CR respectively. There were no differences in OR rates in both groups based on concurrent EPaG exposure: 61% vs. 46% with and without EPaG, respectively, in the OLDER group (p=0.5) and 74% vs 60%, respectively, (p=0.38) in the YOUNG group. On logistic regression analysis using baseline platelet counts, PB lymphocyte (%), D-A-T mutations, karyotype, and EPaG use as covariates, none affected the odds of OR in the 2 groups. The median TTR was 111 days (range, 10-323 days) and 177 days (51-410) in YOUNG AND OLDER groups, respectively; and this was not affected by EPaG use in either group. At a median follow of 38 months (mos) from ATG initiation (53 mos for the OLDER group and 32 mos for the YOUNG group), the median RFS was 49 mos and 39 mos (p=0.6) and median OS 55 vs. not reached (NR) (p <0.0001) in OLDER and YOUNG groups respectively (Fig.1). Significantly more pts in the YOUNG group underwent a subsequent SCT (19% vs. 5%) due to loss of response/ no response, possibly accounting for the higher OS rates. Rates of transformation to MDS or AML was 5% in both groups. Conclusion: Frontline ATG based IST in older pts with AA is a feasible and safe treatment option with promising response rates of 56% and median RFS more than 4 years; figures which are comparable to younger pts with AA treated with IST. The overall risks of transformation to MDS/AML on long term follow-up remain low (≈5%). Further studies assessing the response of the ATG+EPaG combination in these pts and the possibilities of clonal evolution with time needs to be conducted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prognostic Analysis According to European Leukemianet 2022 Risk Stratification for Elderly Patients with Acute Myeloid Leukemia Treated with Decitabine

The European LeukemiaNet (ELN) recently published the revised risk stratification system for AML in 2022 (ELN-2022). The risk stratification of ELN-2017 is generally focused on younger patients who are fit on standard induction treatment. Prognostic impact of the ELN risk stratification for elderly patients who treating low intensity chemotherapy is well not established. This retrospective cohort aimed to evaluate the prognostic significance of the revised ELN-2022 risk stratification in elderly patients treated decitabine chemotherapy. Total 123 patients with elderly AML were eligible. Based on 2022 ELN risk stratification, 14 (11.4%) patients were classified as favorable, 53 (43.1%) as intermediate risk, and 56 (45.5%) as the high risk, respectively. The ELN-2022 classification re-assigned 27 (21.2%) of patients into more adverse-risk group, and 2 (2.4%) of patients into more favorable-risk group compared with the ELN-2017 recommendations. This difference was largely due to the FLT3-ITD allelic ratio which is no longer considered in the ELN 2022 risk classification. Moreover, myelodysplasia-related gene mutations including EZH2, SF3B1, SRSF2, STAG2, U2AF1 genes is now indicated as adverse risk which was another important change compared to previous ELN risk stratification. Because elderly patients highly associated with AML following prior MDS or MDS/MPN, the revised ELN-2022 is well presented an adverse prognosis in elderly AML patients. The rate of CR and CRi was 16.3% (20/123, CR = 8 patients, CRi =12 patients). There was no difference in overall response rate by ELN-2017 and ELN-2022 risk stratification. According to the ELN-2017 classification, the difference of 2-year overall survival (OS) between each risk group was not significant in 123 elderly patients treated decitabine (median OS of ELN-2017 favorable (n = 22), 7.2 months; intermediate-risk (n = 62), 8.0 months; Adverse-risk (n=39), 5.2 months; P = 0.081). In the revised 2022-ELN, the 2-year OS of each risk group was more distinct in elderly patients, compared to ELN-2017(median OS of ELN-2022 favorable (n = 14), 10.4 months; intermediate-risk (n = 53), 7.6 months; Adverse-risk (n=56), 5.5 months; P = 0.053). The study presents the prognostic significance of revised 2022-ELN risk stratification in elderly AML patients receiving decitabine. This study suggests the possibility that the 2022-ELN classification could be predict survival in patients with AML for whom intensive induction therapy is not candidate. Figure legendsFigure 1. Kaplan-Meier curves in patients with elderly AML according to (a) 2017-ELN (b) 2022-ELN. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of Allelic State on Overall Survival in TP53-mutant Acute Myeloid Leukemia (AML) and Higher Risk Myelodysplastic Syndromes (HR-MDS)

Introduction: Mutations in TP53 confer an adverse prognosis in patients (pts) with AML and HR-MDS. There are conflicting results regarding the prognostic impact of mono-allelic vs bi-allelic and mono-hit vs multi-hit TP53 mutation status on prognosis in AML and HR-MDS. Additionally, assessment of loss-of-heterozygosity (LOH) status is not routinely available in many settings limiting the clinical implementation of TP53 mutational status. Methods: We took advantage of a large, randomized study with extensive clinical and molecular annotation to analyze 61 patients (pts) with TP53-mutated (TP53-mut) disease and to compare them to 144 TP53 wild-type pts. All pts received azacitidine and half were randomized to receive the anti-PDL1 antibody durvalumab, which did not improve clinical outcomes (Zeidan et al. Blood Advances 2022). A 38 gene-targeted myeloid mutation analysis from screening bone marrow was performed at Munich Leukemia Laboratory. Only pathogenic TP53 variants with variant allele frequency (VAF) ≥2% were included. Pts with a common SNP or VUS in the TP53 gene were classified as TP53-WT in the analysis. Multi-hit TP53 mutations were defined as previously published by the International Consensus Conference (ICC; Arber et al. Blood 2022) as ≥2 distinct TP53 mutations (VAF ≥10%) or a single TP53 mutation associated with either: 1) cytogenetic deletion involving chromosome 17p (e.g., del(17p) or monosomy 17); 2) a VAF of >50%; or 3) with any complex karyotype. We also defined multi-hit TP53 mutations as proposed by Grob et al. (Blood 2022) as (I) ≥2 TP53 gene variants irrespective of VAF, (II) ≥1 TP53 gene variant co-occurred with a cytogenetic deletion involving chromosome 17p, or (III) TP53 mutations with VAF >55%. Based on multiple prior studies (Grob et al. Blood 2022, Weinberg et al. Blood Advances 2022) patients with AML and HR-MDS with TP53 mutations were analyzed as one disease entity. Results: 37 had TP53-mut AML, 89 were TP53-WT AML, 24 had TP53-mut HR-MDS, and 55 were TP53-WT HR-MDS pts. The average VAF for TP53 mutations was 37%, and 90% had ≥10% VAF. 93% of TP53 mutations occurred in the p53 DNA-binding domain. TP53-mut pts had fewer co-occurring mutations compared with TP53-WT pts (mean number of mutations: 1.8 [SD: 0.77] for TP53-mut pts (including TP53) vs 2.9 [SD: 1.4] for TP53-WT pts; Wilcoxon P <0.001) with distinct patterns in the distribution of co-occurring mutations. In terms of TP53 allelic status, 22 (11.0%) were mono-hit and 41 (20.5%) pts were multi-hit as defined by Grob et al, while 7 (3.4%) and 56 (28.0%) pts were classified as mono-hit and multi-hit per ICC definition, respectively. In the AML cohort, TP53-mut pts were more likely to have poor-risk cytogenetics (59.5% vs 11.2%; p<0.001), therapy-related myeloid neoplasm (10.8% vs 1.1%; p=0.042), and lower bone marrow blast percentage (27.5% vs 35.5%; p=0.001) compared to TP53-WT. Among MDS pts, TP53-mut pts were more likely to have secondary MDS (20.8% vs 1.8%; p=0.013), very poor risk cytogenetics by IPSS-R (75% vs 14.6%; p<0.001), and very high risk IPSS-R score (62.5% vs 34.6%; p=0.039). There were no statistically significant differences in terms of baseline demographics and other clinical characteristics. There was no difference in overall response rate (ORR) between TP53-mut and TP53-WT pts (AML: ORR: 35.1% [95% CI: 20.7% - 52.6%] vs. 33.7% [95% CI: 24.2% - 44.6%]; p=1.000; MDS: ORR: 41.7% [95% CI: 22.8% - 63.1%] vs. 60.0% [95% CI: 45.9% - 72.7%]; p=0.208). TP53 allelic status did not influence OS using either definition (Grob et al: mono-hit: median OS 7.6 months [95% CI:5.4-10.6 months]; multi-hit 10.6 months [95% CI: 9.1-13.0 months] (Figure A); ICC definition: 8.0 months (95% CI: 6.1-20+ months) and 9.5 months [95% CI: 7.7-10.9 months], (Figure B)) and was inferior to TP53-WT (median OS: 18.9 months; 95% CI: 15.5-22.9 months). Conclusion: Outcomes of AML and MDS pts with TP53 mutations are worse compared to TP53-WT without differences between mono-hit vs multi-hit status as defined by the ICC and Grob et al. This suggests that either the negative prognostic impact of a multi-hit TP53 allelic status can be overcome by treatment with azacitidine or that a distinction by TP53 allelic status in newly diagnosed AML/HR-MDS pts treated with azacitidine does not provide additional prognostic information. Whether incorporating TP53 LOH status is necessary to further refine risk assessment warrants additional studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of the efficacy and safety of 2 low-dose rituximab regimens in the second-line treatment of primary immune thrombocytopenia in children

Objective: To compare the efficacy and safety of 2 low-dose rituximab regimens in the treatment of children with primary immune thrombocytopenia (ITP). Methods: A total of 90 ITP children admitted to the Hematology Oncology Center of Beijing Children's Hospital from January 2018 to March 2021 were enrolled in this prospective cohort study. In the single-dose group, rituximab was given with a single dose of 375 mg/m2 (maximum dose 600 mg). In the 4-dose group, rituximab was given with a dose of 100 mg weekly (if body weight of the patient ≥ 30 kg, increase dosage to 200 mg weekly) for 4 weeks. Wilcoxon Mann-Whitney test, Chi-square test and Fisher's exact test were used to analyze the difference in efficacy, safety and treatment burden between two groups. Results: Among the 90 children, 41 were male and 49 were female, and the age of medication was 6.8 (4.1,10.0) years. There were 27 cases in the single-dose group and 63 cases in the 4-dose group.There were no significant differences in overall response rate, complete response rate and partial response rate between the single-dose group and 4-dose group (41% (11/27) vs. 33% (21/63), 26% (7/27) vs. 19% (12/63), 15% (4/27) vs. 14%(9/63), χ2=0.45, 0.54, 0.00, all P>0.05). The single-dose group was earlier to get overall response than the 4-dose group (1 (1, 1) vs. 3 (2, 6) weeks, Z=-3.24, P=0.001). There were no significant differences in the sustained response rate, the overall response rate in 1 year, the complete response rate in 1 year, and the partial response rate in 1 year between the single-dose group and the 4-dose group (33% (9/27) vs. 30% (19/63), 30% (8/27) vs. 24% (15/63), 19% (5/27) vs. 14% (9/63), 11% (3/27) vs. 10% (6/63), χ2=0.09, 0.34, 0.04, 0.00, all P>0.05). There were no significant differences in the duration of overall response, recurrence rate within half a year and one year, recurrence time and rate of adverse events between the single-dose group and 4-dose group (all P>0.05). The number of hospitalizations, the duration of hospital stays and the dosage of the single-dose group were significantly lower than those of the 4-dose group (1 (1, 1) vs. 4 (4, 4) times, 5 (4, 7) vs. 8 (5, 8) d, 400 (250, 500) vs. 400 (400, 800) mg, Z=-8.67, -3.03, -4.05, all P<0.05). Conclusions: The single-dose rituximab regimen is comparable to 4-dose rituximab regimen in effectiveness and safety for treatment of children ITP, but more economical and convenient. The single-dose rituximab regimen is more suitable for the second-line treatment of children ITP.

1719P Predictive value of DNA repair gene alterations for the response to platinum-based chemotherapy and immunotherapy in advanced solid tumors patients: Results from a single center molecular screening program

Homologous recombination DNA repair deficiency is associated with sensitivity to platinum in certain cancer types, including breast, ovarian, pancreatic, and prostate. We aimed to characterize the antitumor activity of platinum-based therapies in patients (pts) with unselected advanced solid tumors for who a DNA repair gene alteration (DNA-RGA) was identified through a tumor molecular screening program (TMSP). All comers pts from the TMSP of Institut Bergonié, Bordeaux, France, were reviewed. Each DNA-RGA identified was classified as pathogenic (P), probably pathogenic (PP), unknown pathogenecity (UP) according to OncoKB and/or ClinVAR databases and defined 3 pts groups. Between January 2018 and May 2020, 662 pts were screened. 199 tumor DNA-RGA were found in 121 (27.7%) pts. The most frequent mutations were : ATM (N=40), POLE (N=23), BAP1 (N=19), BRCA2 (N=16), PMS2 (N=9), ATR (N=9), MSH2 (N=8) and BRCA1 (N=8). 96 pts received platinum-based chemotherapy in the advanced setting, mostly lung cancer pts (N=28). Platinum was carboplatin in 46 (48%) of the pts. No difference in overall response rate (ORR) under platinum regimen was observed between the 3 (P,PP,UP) pts groups. Median progression free survival (PFS) was 8.4 months (IC95% : 7 – 9.4). The only predictor of worst PFS in Cox regression model was the existence of a P alteration compared to the UP group: HR=2.11 (95%CI = 1.2 – 3.7), P = 0.0094. The UP group had a better 6-months PFS compared to the P/PP group: 81% vs 60%, p=0.0382. 48/96 pts received a immune checkpoint inhibitor (ICI) alone or in combination. Interestingly we observed a trend in an increased ORR to ICI according to the DNA-RGA status : 1/11, 5/16, 9/20 pts (p=0.14; Chi-2 test for trend in proportions: p=0.04) in the UP, PP and P group respectively. The same trend was observed on PFS with a 6-months PFS of 11, 44 and 50% in the UP, PP and P groups respectively (p=0.37). P/PP DNA-RGA impacted the PFS but not the ORR to platinum in advanced solid tumors pts. Though the limited population size, this exploratory study paves the way for further investigations evaluting DNA-RGA as biomarkers of response to ICI.

Comparison of a web-push vs. mailed survey protocol in the Monitoring the Future panel study among adults ages 35 to 60

Introduction:Updating the mode of data collection may affect response rates or survey results. The ongoing, national Monitoring the Future (MTF) panel study has traditionally used mailed paper surveys. In 2018, MTF experimented with a web-push data collection design for young adults ages 19–30, concluding that the web-push design improved response rates and did not change substance use estimates after controlling for sociodemographic characteristics (Patrick et al., 2021). The current study sought to replicate the web-push experiment with MTF adults ages 35 to 60 in 2020. Methods:In 2020, the MTF panel study included an experiment to test a web-push protocol for respondents ages 35 to 60 (N=14,379). Participants were randomized to the web-push (i.e., a web survey invitation, with paper surveys available for non-respondents) or traditional MTF (i.e., mailed paper surveys) data collection condition. Results:Results indicated no significant difference in overall response rate for the web-push vs. standard MTF conditions in this age group. Differences in reported estimates of past 30-day substance use prevalence by condition were not significant after adjusting for sociodemographic characteristics. In multivariable models, participants in the web-push condition were less likely to respond via web (than paper) if they were Black, smoked cigarettes in the past 30 days, were unmarried, or did not have a college degree. Conclusions:Overall, the move to the web-push design had minimal impact on response rates and substance use prevalence estimates for this age group. However, in the web-push condition, sociodemographic differences were associated with mode of response.

The Application of Nimotuzumab Combined With Definitive Chemoradiotherapy Toward the Treatment of Locally Advanced Cervical Esophageal Carcinoma: A Retrospective Study.

ObjectiveTo evaluate the safety and effectiveness of nimotuzumab in combination with chemoradiotherapy for locally advanced cervical esophageal squamous cell carcinoma.MethodsRetrospective analysis was conducted from September 2012 to February 2017 among 50 locoregional-advanced cervical esophageal carcinoma (CEC) patients who received concurrent chemoradiotherapy (CRT) combined with or without nimotuzumab at Ningbo Medical Center Lihuili Hospital. Intensity-modulated radiotherapy (IMRT) was administrated on all patients. All patients were divided into two groups, of which 26 (Group A) received 200 mg (22 of 50) or 400 mg (4 of 50) of nimotuzumab per week with CRT and 24 (Group B) received definitive CRT.ResultsThe median follow-up time was 23 months. The median overall survival (OS) and progression-free survival (PFS) were 40.6 and 21.1 months for all, respectively. The 1-, 2-, and 3-year OS rates on the whole were 79.6%, 62.1%, and 47.8%. There was no statistical difference in overall response rate and disease control rate between the two groups. Patients treated with nimotuzumab (group A) had better PFS than the definitive CRT group (group B) (P < 0.05). However, the median OS was 41.4 months in group A and 32.4 months in group B, respectively (P = 0.517). Multivariate analysis showed that PFS among those with lower Eastern Cooperative Oncology Group (ECOG) score (HR = 5.11; P < 0.01), stage II (HR = 9.52; P < 0.01) and the application of nimotuzumab combined with CRT (HR = 0.16; P < 0.01) was much longer. Furthermore, ECOG, stage, C-reactive protein (CRP) baseline, and histological grade can also be used as independent predictors of OS. Grade >3 adverse reactions were not observed. The most common adverse event related to nimotuzumab was mild fever and the occurrence rate was 19% (5 of 26). The incidence of anemia was 65.4% in group A and 87.5% in group B (P < 0.05).ConclusionsFor locoregional-advanced CEC, nimotuzumab combined with IMRT and concomitant chemotherapy was tolerated and effective. In addition, patients with a normal pretherapeutic serum CRP level (CRP < 10 mg/L) can achieve better OS.

P-15 Histology classification highlights the difference in the effectiveness of S-1 over capecitabine when combined with cisplatin in patients with HER2-negative unresectable advanced or recurrent gastric cancer with measurable disease

As there is no clear preference between S-1 plus cisplatin (SP) and capecitabine plus cisplatin (XP) as first-line therapy for patients with HER2-negative unresectable advanced or recurrent gastric cancer with measurable disease, we performed an integrated analysis of three phase II randomized trials (HERBIS-2, HERBIS-4A, and XParTS II) with the use of individual participant data (IPD) from each trial. The aim of this trial was to investigate any differences in therapeutic efficacy between SP and XP for this subset, by focusing on the differences in histology. IPD from three randomized phase II trials were collected where patients received either SP [S-1 (40–60 mg twice daily for 21 days) plus cisplatin (60 mg/m2 on day 8), every 5 weeks] or XP [capecitabine (1000 mg/m2 twice daily for 14 days) plus cisplatin (80 mg/m2 on day 1), every 3 weeks]. Overall, SP (n=79) vs. XP (n=83) showed significantly better overall survival (median OS, 14.2 vs. 11.0 months; hazard ratio [HR], 0.704; P = 0.048) and time to treatment failure (median TTF, 4.7 vs. 3.8 months; HR, 0.664; P= 0.011) and a trend toward better progression-free survival (median PFS, 5.9 vs. 5.1 months; HR, 0.717; P = 0.052), whereas no difference in overall response rate (ORR, 47.5% vs. 50.6%). Despite no difference of ORR by histological classification, the differentiated tumors showed significantly better OS but not PFS or TTF of SP against XP, due to a deeper tumor shrinkage of SP over XPas demonstrated by the fact that cases achieved >60% reduction were significantly more common in SP than in XP (28.2% [11/39] vs. 6.7% [2/30]; P = 0.029, Fisher’s exact test). The undifferentiated tumors showed a consistent better trend of OS, PFS and TTF of SP vs. XP, likely as cases without tumor shrinkage tended to be less in SP than XP (2.6% [1/38] vs. 13.0% [6/46]; P=0.121, Fisher’s exact test). Our subgroup analysis further identified that a significant benefit of SP vs. XP was found in OS for differentiated tumors with a tumor reduction of 30% or more [SP, 23.7 months (95%CI, 13.2-NA) vs. XP, 11.7 months (95%CI, 7.8-19.6); HR of 0.339 (95 % CI 0.163–0.705), interaction P = 0.003], strongly suggesting that deeper tumor shrinkage by SP vs. XP contributed most to OS in the differentiated tumors. Our data showed that SP is superior to XP in this setting, but there is a qualitative difference between the effects of SP and XP, which depends on the histological type of the tumor. For the undifferentiated tumors, SP has fewer treatment failures than XP, reflecting better PFS, OS, and TTF in SP than XP. For the differentiated tumors, SP achieves deeper tumor shrinkage than XP, which contributes to longer OS, but not PFS or TTF. Further study is needed to determine whether these differences of S-1 vs.capecitabine are reproduced by the combination of oxaliplatin and immune-checkpoint inhibitors, the new standard of care for HER2-negative unresectable advanced or recurrent gastric cancer.

The Treatment of Newly Diagnosed Primary Immune Thrombocytopenia by Recombinant Human Thrombopoietin Combined with Glucocorticoid

To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of newly diagnosed adult primary immune thrombocytopenia (ITP). Eleven male and 23 female patients with the diagnosis of primary ITP in our hospital from November 2018 to October 2019 were enrolled and randomly divided into test group (17 cases) and control group (17 cases), the median age was 52 years old (range: 20-76 years old). The patients in test group were treated with rhTPO 300 IU/(kg·d) combined with glucocorticoid , while the patients in control group were treated with rhTPO (15 000 IU/d) combined with glucocorticoid. Platelet count, platelet increase, as well as the overall response rate were compared. At the same time, the drug tolerance and any adverse drug reactions were observed. The platelet counts and platelet increase of the patients in the test group were significantly higher than those in control group (P<0.05). There was no significant difference in platelet counts and platelet increase between the patients in the test group and control group at day 3, 7 after treatment. There was no significant difference in overall response rates and complete response rates at day 7, 14 between the two groups either. In test group, there were 13 cases received platelet transfusion, while 12 cases in control group. The muscle aches occurred in one patient, and mild aminotransferase increased in another patient in test group which was self-recovery without treatment. RhTPO 300 U/(kg·d) combined with glucocorticoid could rapidly increase the platelet count with a low incidence of tolerable adverse events compared with conventional dose rhTPO with glucocorticoid.

Clinical efficacy of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation: a prospective randomized controlled trial

To study the clinical efficacy, advantages, and disadvantages of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation (OOC). A total of 168 children with OOC were enrolled in this prospective study. All the subjects were randomly divided into a test group and a control group based on the order of visiting time, 84 in each group. The test group was treated with adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder, and the control group was treated with oral administration of compound polyethylene glycol 4000-electrolyte powder alone. Eleven children in the test group and two children in the control group withdrew from the study since they could not finish the whole treatment course. Finally, 73 children in the test group and 82 children in the control group were included in this analysis. As clinical outcomes, the total score of clinical symptoms and overall response rate were compared between the two groups at weeks 4 and 8 of treatment. There was no significant difference in the total score of clinical symptoms between the two groups at beginning of treatment and at week 4 (P>0.05), while the test group had a significantly lower total score of clinical symptoms than the control group at week 8 (P<0.05). At week 4, there was no significant difference in overall response rate between the two groups (P>0.05), while the test group had a significantly higher overall response rate than the control group at week 8 (P<0.05). Adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder is significantly associated with improvement of clinical outcomes in the treatment of children with OOC.