Non-hematologic Adverse Reactions Research Articles

Clinical Characteristics and Survival Analysis of Single Center Adult Chronic Myeloid Leukemia in Chronic Phase

To investigate the clinical characteristics and prognosis of single center adult chronic myeloid leukemia in chronic phase (CML-CP). Clinical data of 41 adult CML-CP patients in Department of Hematology, Shanghai Fengxian District Central Hospital from January 2015 to May 2021 were retrospectively analyzed. The clinical characteristics and prognosis of patients between <60 years group and ≥60 years group were compared. The 41 patients included 27 (65.9%) males and 14 (34.1%) females. The median age of the patients was 56(19-84) years, with 22 cases (53.7%) <60 years and 19 cases (46.3%) ≥60 years. Univariate analysis indicated that the proportions of patients with comorbidities, intermediate/high-risk Sokal score, myelofibrosis, and lactate dehydrogenase ≥1 000 U/L were significantly increased in ≥60 years group compared with <60 years group at initial diagnosis (all P <0.05). There were no statistical differences in the distribution of sex, ELST score, white blood cell count, platelet count, peripheral blood basophil percentage, peripheral blood eosinophil percentage and bone marrow primitive cell percentage between the two groups (P >0.05). The proportion of patients taking reduced-dose imatinib in ≥60 years group significantly increased (P <0.001). Patients <60 years had a higher proportion of molecular biological remission after treatment of tyrosine kinase inhibitors (TKIs) than patients ≥60 years (P <0.001). The incidence of non-hematologic adverse reactions to TKI therapy significantly increased in patients ≥60 years (P <0.001). Multivariate analysis showed that no adverse factors affecting the efficacy and prognosis of TKI. Compared with adult CML-CP patients <60 years, patients ≥60 years gain fewer benefits from TKI treatment and increased adverse reactions.

The efficacy and safety of avapritinib in the treatment of molecular biologically positive core binding factor-acute myeloid leukemia with KIT mutation after allogeneic hematopoietic stem cell transplantation

Objective: To investigate the efficacy and safety of avapritinib in the treatment of molecular biologically positive core binding factor-acute myeloid leukemia (CBF-AML) with KIT mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: We retrospectively analyzed the clinical data of six patients with molecular biologically positive CBF-AML with KIT mutation after allo-HSCT, who were treated with avapritinib at Henan Cancer Hospital from December 2021 to March 2023, and evaluated the efficacy and safety of avapritinib. Results: After 1 month of treatment with avapritinib, the transcription level of the fusion gene decreased in six patients, and the transcription level decreased by ≥1 log in five patients. In four patients who received avapritinib for ≥3 months, the fusion gene turned negative, and the median time to turn negative was 2.0 (range: 1.0-3.0) months. Up to the end of follow-up, four patients had no recurrence. The most common adverse reaction of avapritinib was myelosuppression, including neutropenia in two cases, thrombocytopenia in two cases, and anemia in one case. The non-hematological adverse reactions were nausea in two cases, edema in one case, and memory loss in one case, all of which were grades 1-2. Conclusion: Avapritinib was effective for molecular biologically positive CBF-AML patients with KIT mutation after allo-HSCT. The main adverse reaction was myelosuppression, which could generally be tolerated.

Modified SMILE (mSMILE) is active in the treatment of pediatric Epstein-Barr virus-associated natural killer/T-cell lymphoma: a single center experience, case series.

The Epstein-Barr virus-associated natural killer (NK) and T-cell lymphoma (EBV + NK/T cell lymphoma) is a severe illness mainly affecting children and young adults, often resulting in a poor prognosis. To date, there is no consensus on an established treatment strategy. This study aims to evaluate the efficacy and safety of the mSMILE (modified steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen in treating EBV+ NK/T-cell lymphoma and to provide insights into potential treatment outcomes. In this study, we conducted a retrospective analysis of the clinical data and treatment outcomes for patients with EBV + NK/T cell lymphoma treated at Children's Hospital of Nanjing Medical University between July 2017 and January 2022. These patients received at least two cycles of the mSMILE chemotherapy, in which a single dose of pegaspargase was substituted for 7 doses of L-asparaginase per cycle. Eight patients were included in the study: one with extranodal NK/T-cell lymphoma, one with primary nodal NK/T-cell lymphoma, and six with Systemic EBV+ NK/T cell lymphoma of childhood. The results showed that five patients achieved complete remission, two achieved partial remission, and one showed progressive disease, resulting in a complete remission rate of 62.5% and an overall response rate of 87.5%. The 3-year overall survival (OS) and event-free survival (EFS) rates were 87.5% and 75%, respectively. The most common adverse reactions associated with chemotherapy were hematologic toxicities of stages III to IV. Nonhematologic adverse reactions mainly included impaired liver function, infections, and oral mucositis, which were resolved with aggressive anti-infective therapy. Based on our clinical experience, the mSMILE appears to be a safe and effective treatment option for EBV + NK/T-cell lymphoma, meriting further investigation in late-phase clinical trials.

The Reduction of CD4+ T Lymphocytes after the Treatment of Follicular Lymphoma with the Bendamustine Containing Regimen May Predict the Occurrence of Infection and Efficacy

To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine. The clinical data of 129 FL patients who were treated with Bendamustine containing regimen were collected from January 1,2020 to October 30,2022 in the Hematology Department of Lianyungang Second People's Hospital and Jiangsu Provincial People's Hospital. The patients were divided into three groups: Bendamustine plus Rituximab (BR), Bendamustine plus Obinutuzumab (GB), Rituximab + Cyclophosphamide + Epirubicin / Doxorubicin + Vindesine + Prednisone (R-CHOP). The efficacy, safety and related prognostic factors of the treatment of FL with a regimen based on Bendamustine were retrospectively analyzed. The ORR was 98% for the BR group, 94% for the GB group, and 72.3% for the R-CHOP group, while the CR rate was 61.2%,70% and 40.4%, respectively. The ORR and CR rates of the R-CHOP group were statistically different from those of the BR group and GB group (P < 0.05). The 3-year PFS rate of the BR group, GB group, and R-CHOP group was 89.6%, 90.9%, 48.9%, respectively. There was a statistically significant difference in 3-year PFS between the R-CHOP group, BR group, and GB group (P < 0.05), while there was no statistically significant difference in 3-year OS（P ＞0.05）. Hematological adverse reactions were mainly bone marrow suppression. Lymphocytes and CD4+T lymphocytes decreased to the lowest level about 6 months after treatment, and the incidence of lymphopenia in BR group and GB group was higher than that in R-CHOP group, with a statistical difference (P < 0.05). The higher incidence of non-Hematological adverse reactions were pulmonary infection, EB virus infection, hepatitis B virus reactivation, and gastrointestinal reactions without statistical difference in 3 groups (P >0.05), and were all controllable. The Receiver operating characteristic of CD4+T lymphocyte count showed that AUC of BR group was 0.802, and the critical value was 258/uL; AUC of GB group was 0.754 with a critical value of 322/uL. The treatment of FL with the Bendamustine containing regimen has good efficacy and controllable adverse reactions, but lymphocytopenia was significant after treatment, and the curative efficacy in combination with various CD20 monoclonal antibodies was different. The lowest CD4+T lymphocyte count can be used as a predictive factor for the occurrence of infection and efficacy of the Bendamustine containing regimen for FL.

Observation on the Clinical Effect of Applying Vinaclat Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P &gt; 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

The Effect and Safety of Flumatinib in Patients with Chronic Myelogenous Leukemia Failed First-and Second-line Treatment

To analyze the efficacy and safety of flumatinib, a second-generation tyrosine kinase inhibitor (TKI) independently developed in China, in patients with chronic myelogenous leukemia in chronic phase (CML-CP) who falied first-line and second-line treatment. The clinical data of 30 CML-CP patients treated with flumatinib in Lianyungang First People's Hospital from January 2020 to September 2022 were collected retrospectively. Among them, 15 patients who received imatinib first-line treatment but failed treatment were included in the second-line group, and the other 15 patients who failed second-line treatment with nilotinib or dasatinib were included in the third-line group. The hematological and molecular responses of the patients in the two groups at 3, 6 and 12 months of treatment, and the event-free survival (EFS) and adverse reactions of patients at the end of follow-up were statistical analyzed. At 3, 6, and 12 months of treatment, 10, 11, and 12 patients in the second line group achieved major molecular response (MMR), which was higher than that of 3, 4, and 5 patients in the third line group (P =0.010, P =0.011, P =0.010). At 3 months of treatment, 12 and 13 patients achieved complete hematological response (CHR) and early molecular response (EMR) in the second-line group, which was higher than that of 9 and 13 patients in the third-line group, but the difference between the two groups was not statistically significant (P =0.232, P =1.000); At 6 and 12 months of treatment, 6 and 7 patients in the second-line group achieved MR4.5, which were higher than of 3 and 2 cases in the third-line group, but the difference was not statistically significant (P =0.427, P =0.713). The hematological adverse reactions of patients in the second-line group during treatment the period were mainly grade 1-2 thrombocytopenia and anemia, and no grade 3-4 of adverse reactions occurred. In the third-line group, there were 2 cases of grade 1-2 thrombocytopenia, grade 1-2 anemia and white blood cell 3 cases were reduced each, 1 case of grade 3-4 anemia, 2 cases of grade 3-4 neutropenia. The non-hematological adverse reactions in the second-line group were rash (2 cases), headache (1 case), diarrhea (1 case), fatigue (1 case), limb pain (1 case). There were 1 cases of diarrhea, 1 cases of nausea, and 1 cases of edema in the third-line group. There was no statistical significance in hematological and non-hematological adverse reactions between the two groups of patients (P >0.05). At the end of follow-up, the EFS rate of patients in the second-line group was higher than that in the third-line group (100% vs 93.3%), but the difference was not statistically significant (P =0.317). The second-generation TKI flumatinib independently developed in China, has good curative effect and safety for CML-CP patients who failed first-line and second-line treatment.

Real-World Efficacy and Safety of China-Made Flumatinib Mesylate in the Treatment of Chronic Myeloid Leukemia in Chronic Phase

To evaluate the efficacy and safty of China-made flumatinib mesylate in the treatment of chronic myeloid leukemia in chronic phase (CML-CP). 42 CML-CP patients treated with Chinese produced flumatinib (oral, 600 mg, 1/d) were included in the study, including 14 newly diagnosed patients and 28 patients underwent conversion therapy. The hematological, cytogenetic and molecular response and safety were observed and evaluated after 3, 6 and 12 months of treatment. 35 patients were treated for more than 3 months, among which 31 patients were treated for more than 6 months and 17 patients were treated for more than 12 months. After 3 months of treatment, 33 patients underwent hematological, cytogenetic and molecular examination. Of these, 32 patients achieved complete hematological response (CHR), 13 patients achieved complete cytogenetic response (CCyR), 20 patients showed BCR-ABLIS≤10% and 7 patients reached major molecular response (MMR). After 6 months of treatment, all 30 patients who could evaluate efficacy achieved CHR, of which 17 patients achieved CCyR, 18 patients showed BCR-ABLIS≤1% and 16 patients reached MMR. After 12 months of treatment, all 17 patients were evaluated for efficacy, all achieved CHR, 10 patients obtained CCyR, 7 patients reached MMR. Grade III or IV thrombocytopenia, leukopenia and anemia occurred in 7, 2 and 1 patients, respectively. The non-hematological adverse reactions were diarrhea in 6 cases, renal function damage in 4 cases, rash and pruritus in 3 cases, liver function damage in 3 cases, nausea in 1 case, fever in 1 case, bone/joint or muscle pain in 1 case. In the real world, China-made flumatinib mesylate has a positive short-term efficacy and reliable safety in the treatment of CML-CP patients, whether as first-line treatment or second- and third-line conversion therapy.

Efficacy and safety of pegylated interferon alpha-2b for patients with myeloproliferative neoplasm

Objective: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG-IFN-α2b) in the treatment of myeloproliferative neoplasm (MPN). Methods: Thirty-four MPN patients receiving PEG-IFN-α2b treatment in the Second Hospital of Tianjin Medical University from August 2019 to October 2022 were prospectively included. Among the patients, 9 were male and 25 were female, and the median age [M (Q1, Q3)] was 57 (19, 78) years. Patients' clinical characteristics were collected and the follow-up was performed. As of January 30, 2023, the follow-up period [M(Q1, Q3)] was 24 (16, 33) months. The efficacy, safety and changes in immune cell and cytokine levels after 12 and 24 months of treatment were analyzed. Results: During the follow-up period, 4 patients dropped out, and the efficacy was evaluable in 30 patients. Following 12 and 24 months of treatment, the complete hematologic response (CHR) rates were 57.1% (16/28) and 75.0% (18/24), respectively. The complete molecular response (CMR)+partial molecular response (PMR) rates were 27.3% (6/22) and 55.0% (11/20), respectively. The bone marrow histopathological overall response rates (ORR) were 34.6% (9/26) and 47.6% (10/21), respectively. At 12 and 24 months of treatment, the proportions of CD8+HLA-DR+T cells, effector T cell subpopulations, CD56bright natural killer (NK) cells, and plasmacytoid dendritic cells (pDC) were higher than the pre-treatment levels, while the proportion of CD56dim NK cells was lower than the pre-treatment level (all P<0.05). The levels of motif chemokine ligand 10 (CXCL10), tumor necrosis factor (TNF)-α and TNF-β in bone marrow all increased from those prior to treatment, while the levels of vascular endothelial growth factor (VEGF) and interleukin (IL-4) decreased from those prior to treatment (all P<0.05). Among hematological adverse reactions, white blood cells decrease [47% (16/34)] was observed with high incidence. Among non-hematological adverse reactions, asthenia [44.1% (15/34)] and transaminases increase [32.3% (11/34)] were observed with high incidences. Conclusions: PEG-IFN-α2b has high hematologic, molecular, and bone marrow histopathological response rates in the treatment of MPN. It can reduce malignant clone loads and regulate the immune microenvironment and is safe and well tolerated overall.

Efficacy and Safety Analysis of Carfilzomib-Containing Regimen in the Treatment of Multiple Myeloma：a Multicenter Real-World Study

Purpose To investigate the efficacy and safety of carfilzomib-containing regimens in the treatment of multiple myeloma（MM） in different lines of treatment. method The clinical data of 55 multiple myeloma patients who received carfilzomib treatment in 10 medical centers in Shandong from January 2022 to March 2023 were retrospectively analyzed , and grouped according to the number of MM treatment lines, they were divided into group A : newly diagnosed multiple myeloma ( NDMM ), group B : patients with first relapse, and group C : patients treated with carfilzomib in the third line or above. Del ( 17p ), t ( 4;14 ), t ( 14;16 ) were defined as high-risk cytogenetic abnormalities result All patients with multiple myeloma were treated with the combined regimen based on carfilzomib, including 24 patients in group A , 9 patients in group B , and 22 patients in group C. Among all patients, there were 27 cases ( 49.1% ) of high-risk cytogenetics, and 13 cases with ECOG score ≥ 3 points ( 23.6% ), 10 cases ( 18.2 ) had eGFR &amp;lt;30 ml/min. The median follow-up time of patients in group A , group B and group C was 8 months, 9 months and 8 months. The overall response rate ( ORR ) was 91.7% , 88.9% and 77.3% for patients in Arms A , B and C who started carfilzomib, respectively . The ≥very good partial response ( VGPR ) rates were 75% and 66.7% for Arm A and B patients , respectively , while the ≥VGPR rate for Arm C patients was 41.0% . The negative rate of minimal residual disease ( MRD , sensitivity: 10 -6 ) in group A was 62.5% ( 15/24 ). Follow - up deadline is March 2023 On the 31st , the median progression-free survival ( PFS ) time and median overall survival ( OS ) time of patients in the three groups were not reached. After the application of carfilzomib, the incidence rate of grade 3-4 adverse events ( AE ) was 32.7% ( 18/55 ). The main hematological adverse reactions were anemia, thrombocytopenia, lymphopenia and neutropenia. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections. in conclusion Carfilzomib-based regimens in the treatment of multiple myeloma have good curative effect and safety, and the first-line and first-time relapse patients have better curative effect.

FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma.

In January 2023, the FDA granted accelerated approval to pirtobrutinib for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Approval was based on BRUIN, a single-arm study of pirtobrutinib monotherapy in patients with B-cell malignancies. Efficacy was based on independent review committee-assessed overall response rate (ORR) supported by durability of response in 120 patients with relapsed or refractory MCL who had received a prior BTK inhibitor and received the approved pirtobrutinib dosage of 200 mg once daily. The ORR was 50% [95% confidence interval (CI), 41-59], and the complete response rate was 13% (95% CI, 7-20), with an estimated median duration of response of 8.3 months. The most common nonhematologic adverse reactions were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Warnings and Precautions in labeling include infection, hemorrhage, cytopenias, atrial arrhythmias, and second primary malignancies. Postmarketing studies were required to evaluate longer-term safety of pirtobrutinib and to verify the clinical benefit of pirtobrutinib. This article summarizes key aspects of the regulatory review, including the indication statement, efficacy and safety considerations, and postmarketing requirements.

A Retrospective Study on the Efficacy and Safety of Idarubicin Combined with High-Dose Cytarabine Consolidation in Patients with Acute Myeloid Leukemia over 60 Years of Age in First Remission

To evaluate the efficacy and safety of idarubicin combined with high-dose cytarabine as a post-remission therapy for elderly patients with acute myeloid leukemia (AML). From November 2017 to June 2021, 24 AML patients aged ≥60 years who were in complete remission for the first time were enrolled in consolidation chemotherapy with idarubicin (10 mg/m2 intravenously once for day 1) combined with high-dose cytarabine (1.5 g/m2 intravenously over 3 hours every 12 hours for day 1-3), and the efficacy and safety were observed. Among the 24 patients, there were 12 males and 12 females, the median age was 65 (60-78) years old, and the median follow-up time was 23.3 (2-42.7) months. By the end of the follow-up, 15 patients relapsed and 11 patients died. The median disease-free survival (DFS) was 9 months and there were 3 cases of 2-year DFS. The median overall survival (OS) was 16.2 months, and there were 4 cases of 2-year OS. In terms of safety, 6 patients had grade 1-2 non-hematological adverse reactions, 12 patients had grade 3-4 hematological adverse reactions, and a total of 6 patients developed infection after consolidation chemotherapy. Multivariate analysis showed that two induction cycles and high-risk cytogenetic abnormalities were the adverse factors of DFS and OS in elderly patients with AML in this study. For AML patients ≥60 years old in first complete remission, idarubicin combined with high-dose cytarabine as post-remission therapy has a better safety, but compared with other regimens does not improve the prognosis of elderly patients, which needs further exploration.

The Efficacy and Safety of Daratumumab-Based Regimen in Treatment of Multiple Myeloma Patients with Renal Impairment

To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI). The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed. The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M2). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections. Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.

Analysis of the Curative Effect and Influencing Factors of Nilotinib Second-line and Dasatinib Third-line on Chronic Myelogenous Leukemia Failed First-line and Second-line Treatment

To evaluate the efficacy of the second-line nilotinib and third-line dasatinib on chronic myelogenous leukemia (CML) with failed first- and second-line treatments, and analyze the influencing factors of the efficacy. Selected 83 patients in The Third People's Hospital of Kunshan City, Jiangsu Province with CML who were treated with nilotinib as the second-line treatment after the failure of the first-line treatment with imatinib as the second-line treatment group (referred to as the second-line group) from January 2014 to December 2018, and 61 CML patients who were treated by dasatinib as the third-line treatment group (referred to as the third-line group) after the failure of the second-line treatment with nilotinib; the first-line treatment with imatinib failed, but due to various reasons, the patients were fully after being informed of the possible serious consequences of not changing the drug treatment, 37 CML patients who were still required to continue imatinib treatment served as the control group. The hematological, genetic and molecular responses of each group were compared for 3, 6, and 24 months of treatment. LogistiC regression was used to analyze the factors affecting the second and third line curative effects. The three groups had statistically significant differences in the rates of achieving CHR, MCyR, and MMR at 3, 6, and 12 months of treatment (P<0.05). Compared the two groups, the CHR rates of the second-line group at 3, 6, and 12 months of treatment were 100.00%, 97.59%, and 95.18%, respectively; higher than the third-line group's 90.16%, 86.89%, 83.61% and the control group's 83.78%, 75.68% and 72.97%; the CHR rate of the third-line group was higher than that of the control group at 6 and 12 months of treatment. The rates of reaching MCyR at 3, 6, and 12 months after treatment in the second-line group were 87.95%, 93.98% and 93.98%, respectively, while those in the third-line group were 80.33%, 88.52% and 86.89%, which were higher than those of the control group of 67.57%, 64.86% and 48.65%. The rates of achieving MMR at 3, 6, and 12 months of treatment in the second-line group were 19.28%, 33.72% and 60.24%, respectively, and those in the third-line group were 11.48%, 26.23% and 49.18%, which were higher than those of the control group of 0.00%, 2.70% and 0.00%; The rate of reaching MMR within 12 months of treatment in the second-line group was higher than that of the third-line group, and the differences was statistically significant (P<0.05). There was no significant difference in the rate of reaching MCyR between the second-line group and the third-line group at 3, 6, and 12 months, and the rate of reaching MMR at 3 and 6 months (P>0.05). The incidence of nausea and vomiting among the three main non-hematological adverse reactions, and the incidence of grade 1~2 anemia among the hematological adverse reactions were statistically significant (P<0.05). There was no significant difference in the incidence of rash, eyelid edema, diarrhea, thrombocytopenia, leukopenia and neutropenia in the three groups (P>0.05). The incidence of nausea and vomiting and grade 1~2 anemia in the second-line group and the third-line group were higher than that of the control group, and the difference was statistically significant (P<0.05). There were statistically significant differences in Sokal score, medication compliance, and hematological adverse reactions between the MMR group and the non-MMR group (P<0.05). Logistic regression analysis showed that dose reduction or withdrawal during the treatment period, and grade 3~4 hematological adverse reactions were the main factors affecting the second and third line curative effects (OR=22.160, 2.715, 95% CI=2.795-93.027, 1.882-48.834). The second-line nilotinib and the third-line dasatinib have a better effect on CML patients who have failed the first and second-line treatments. Grade 3~4 hematological adverse reactions, dose reduction or withdrawal are risk factors that affect the efficacy of second and third-line treatments.

Induction plus adjuvant chemotherapy, combined treatment with nimotuzumab, and intensity-modulated radiation therapy for N3 stage nasopharyngeal carcinoma

The main cause of treatment failure in NPC is distant metastasis and the NPC patients with stage N3 are the most prone to develop distant metastases. Thus, the selection of an efficient, lowtoxicity, welltolerated, adequate regimen is the key to improve the therapeutic efficacy for patients with stage N3 NPC. This study aimed to determine the safety and feasibility of induction chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus cisplatin, combined treatment with nimotuzumab, and Intensity-modulated radiation therapy (IMRT), followed by S-1 adjuvant chemotherapy for stage N3M0 nasopharyngeal carcinoma (NPC). This retrospective study involved 43 patients with stage N3M0 NPC treated with the above regimens. For induction chemotherapy, four cycles of nab-paclitaxel (260 mg/m2, day 1) plus cisplatin (25 mg/m2, days 1-3) were administered. IMRT was performed concurrently with targeted therapy with nimotuzumab (200 mg IV, weekly for seven courses). For adjuvant chemotherapy, S-1 (40-60 mg twice a day, depending on the patient's body surface area) was administered for 14 days and was stopped for 7 days; this cycle was repeated every 21 days. All statistical analyses were performed using an SPSS v21.0 software package. The LRC, OS, DMFS, and progressionfree survival (PFS) rates were calculated using the Kaplan-Meier method, and differences in these rates were analyzed using logrank test. The total treatment efficiency was 100.0%. The 3-year locoregional control, overall survival, distant metastasis-free survival, and progression-free survival rates were 97.6%, 87.6%, 83.5%, and 81.0%, respectively. Neutropenia was the most common hematological toxicity (95.3%), and the incidence of Grade ≥3 neutropenia was 30.2%. Grade 3 anemia and thrombocytopenia did not occur. The most common nonhematological adverse reactions were mucositis (100.0%), hair loss (100.0%), rashes (65.1%), and limb numbness with pain (60.4%). The occurrence and treatment of skin rashes needed special attention. Induction nab-paclitaxel plus cisplatin, nimotuzumab combined with IMRT, followed by S-1 adjuvant chemotherapy, yielded an excellent survival benefit with tolerable toxicities in patients with stage N3 NPC. Distant metastasis was the main cause of treatment failure.

Clinical Efficacy of Autologous Hematopoietic Stem Cell Transplantation for Patients with Diffuse Large B-Cell Lymphoma

To compare the clinical efficacy of first-line and salvage autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of patients with diffuse large B-cell lymphoma (DLBCL). The clinical data of 30 patients with DLBCL aged≤60 years old were retrospectively analyzed, and the patients were divided into first-line auto-HSCT group (15 cases) and salvage auto-HSCT group (refractory relapsed patients, 15 cases) according to the timing of transplantation, and the efficacy was analyzed. Anyone of the factors must be followed in patients receiving first-line HSCT: aaIPI score≥2 points, Ann-Arbor stage III-IV, large mass (diameter≥10 cm) or double expression of c-myc/BCL-2. The median follow-up time for all patients after transplantation was 26 (3-103) months. Until the end of follow-up, 23 patients survived and 7 patients died. All the 7 dead patients with multiple organ failure due to the relapse and disease progression. The median survival time of 7 dead patients from transplantation to death was 6 (3-11) months. Among the 15 patients in the first-line auto-HSCT group, there were 2 patients relapsed (13.3%), 1 dead (6.7%), 14 patients survived [overall survival (OS) rate was 93.3%]. Among the 15 patients treated with salvage auto-HSCT, 6 patients died due to disease progression or relapse (40%), 9 cases survived (OS rate was 60%). There was a statistically significant difference in the mortality of patients between the two groups (6.7% vs 40%, P=0.006). The 3-year PFS and OS rates of patients in first-line auto-HSCT group were both 93.3%. The 3-year PFS and OS of patients in salvage auto-HSCT group were 58.7% and 59.2%. The 3-year OS and PFS of patients in the first-line auto-HSCT group were significantly higher than those in the salvage auto-HSCT group (P=0.03, P=0.04). The bone marrow suppression was the most common adverse complication and all patients showed grade III-IV granulocytopenia. Non-hematological adverse reactions were mainly gastrointestinal adverse reactions and oral mucositis. There was no statistically significant difference in adverse reactions between the two groups. First-line auto-HSCT can be used as a consolidation treatment for DLBCL patients with poor prognostic factors. Auto-HSCT can further improve the prognosis of salvage chemotherapy-sensitive patients with refractory relapsed DLBCL.

The Correlation Between UGT1A1 Gene Phenotypes and the Clinical Prognosis of Advanced Colorectal Cancer After FOLFIRI Therapy

Objective: This study investigated the correlations between the different phenotypes of the uridine diphosphate glucuronyl transferase (UGT) 1A1 gene and the treatment of advanced colorectal cancer after the FOLFIRI regimen. Materials and Methods: A total of 240 advanced colorectal cancer patients with stage IV colon cancer or recurrence after radical surgery between January 2014 and December 2018 were included in a retrospective study. All participants were treated with the FOLFIRI regimen until the disease progressed or an intolerable level of toxicity occurred. Results: In this study, three phenotypes of the UGT1A1 gene promoter were found: the homozygous wild type (TA6/6 type, 78.3%), the heterozygous mutant type (TA6/7 type, 19.6%), and the homozygous mutant type (TA7/7 type, 2.1%). Compared with TA6/7 and TA6/6, the risk of nonresponse to FOLFIRI chemotherapy increased by 16%, but the difference was not significant. The risk of death increased by 24%, and there was no significant difference. There was a risk of hematologic and nonhematologic adverse reactions occurring in TA6/7 and TA6/6, and the total risk of adverse reactions increased by 9.3773 times among patients with more than two metastatic organs. Compared with patients with TA6/6, the risk of toxic side-effects increased by 42.8066 times (p = 0.0259) for patients with TA6/7. Among patients who received FOLFIRI chemotherapy for more than four cycles, the proportion with TA6/7 was greater than that with TA6/6. Compared with those with TA6/6, patients with TA6/7 showed a higher risk of hematologic toxicity (22.3246 times, p = 0.0035). Conclusion: The TA6/7 in patients with advanced colorectal cancer had more than two metastatic organs, and received FOLFIRI chemotherapy for more than four cycles compared with TA6/6 patients. Furthermore, the risk of hematologic and nonhematologic adverse reactions significantly increased, and the risk of digestive-tract and hematologic toxicity was more significant.

Therapeutic Effect of Imatinib Made in Real World to Newly Diagnosed Chronic Myeloid Leukemia

To evaluate the clinical efficacy and safety of domestic imatinib (made in China) in patients with newly diagnosed chronic myeloid leukemia chronic phase(CML-CP). Fifty-seven newly diagnosed CML-CP patients who did not receive any other anti-CML treatment were treated by domestic imatinib 400 mg once a day. The hematological, cytogenetic and molecular reactions and safety were observed and evaluated after 3, 6 and 12 months of treatment. Fifty-six patients were treated for ≥3 and 6 months, among which 50 patients were treated for ≥12 months. After 3 months of treatment, 49 patients underwent hematological examination, 47 patients (95.9%) achieved complete hematological response (CHR), 49 patients underwent cytogenetic examination, 39 patients (79.6%) achieved major cytogenetic response (MCyR), and 12 patients (24.5%) achieved complete cytogenetic response (CCyR). 49 patients underwent the level of BCR-ABL test, including 41 patients (83.7%) with BCR-ABLIS≤10%, and 5 patients (10.2%) with major molecular response (MMR: BCR-ABLIS ≤ 0.1%). After 6 months of treatment, 49 patients underwent hematological examination, and 49 patients (100%) all achieved CHR. 49 patients underwent cytogenetic examined, of which 41 cases (83.7%) obtained MCyR and 31 cases (65.3%) obtained CCyR. 49 patients underwent the level of BCR-ABL test, among which 33 patients (67.4%) showed BCR-ABLIS≤1%, and 15 patients(30.6%) reached MMR. After 12 months of treatment, 45 patients underwent hematological examination, and all the patients (100%) got CHR. 45 patients underwent cytogenetic examined, of which 41 cases (91.1%) obtained MCyR and 35 cases (77.8%) obtained CCyR. 45 cases were tested for BCR-ABL level, and 24 cases (55.3%) reached MMR. The incidence of grade Ⅲ leukopenia, thrombocytopenia and anemia were 14.0%, 8.7% and 10.5%, respectively. Non-hematological adverse reactions were edema (64.9%), nausea (50.9%), vomiting (35.1%), rash (24.5%), fever (15.8%), bone and joint muscle pain (38.6%), diarrhea(17.6%) and liver function damage (3.5%). There were no grade IV hematological and non-hematological adverse reactions. In the real world, Domestics imatinib mesylate is effective and safe in the treatment of newly diagnosed CML-CP patients, but long-term follow-up data are still necessary to verify its long-term efficacy.

The efficacy and safety of daratumumab in relapsed and refractory multiple myeloma

目的探讨达雷妥尤单抗治疗复发/难治多发性骨髓瘤（RRMM）的疗效与安全性。方法回顾性分析2017年9月至2020年3月上海长征医院接受达雷妥尤单抗治疗的46例RRMM患者的临床资料。结果所有RRMM患者均采用以达雷妥尤单抗为基础的方案进行治疗，其中Dd（达雷妥尤单抗+地塞米松）方案组8例，DRd（达雷妥尤单抗+来那度胺+地塞米松）方案组35例，DVd（达雷妥尤单抗+硼替佐米+地塞米松）方案组3例。中位随访9.6个月，可评估疗效患者44例，总缓解率（ORR）75%[完全缓解（CR）率18.2%]。对硼替佐米、来那度胺及两者均耐药患者的ORR分别为70.6%（CR率17.6%）、69.2%（CR率11.5%）和63.6%（CR率13.6%），三组间差异无统计学意义。DRd组、DVd组和Dd组的ORR分别为85.3%、66.7%和28.6%（P＝0.007）。46例患者的中位无进展生存（PFS）时间为8.9个月，中位总生存（OS）时间未达到，1年OS率74%。DRd组中位PFS时间及OS时间较Dd组长（PFS时间：14.4个月对2.0个月；OS时间：未达到对5.2个月）。应用达雷妥尤单抗后，3级以上血液学不良反应以中性粒细胞减少最为常见，非血液学不良反应主要为输液相关不良反应和感染。预后分析显示伴髓外病灶患者的PFS时间和OS时间较不伴髓外病灶患者缩短（PFS时间：5.7个月对14.4个月，P＝0.033；OS时间：6.3个月对未达到，P＝0.029）；ECOG评分3～4分患者的OS时间较ECOG评分1～2分患者缩短（5.9个月对未达到，P＝0.004）。结论以达雷妥尤单抗为基础的方案治疗RRMM具有较好的疗效及安全性。

The safety and efficacy of a novel hypo-fractionated total marrow and lymphoid irradiation before allogeneic stem cell transplantation for lymphoma and acute leukemia

PurposeTotal body irradiation (TBI) has been widely utilized as part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT), but is associated with significant toxicities. Targeted TBI using helical Tomotherapy allows precise and homogeneous tumor coverage and excellent sparing of organs at risk. The purpose of this study was to evaluate the clinical outcomes of a novel hypo-fractionation strategy for patients receiving total marrow and involved lymphoid irradiation (TMLI) as part of the conditioning regimen before HSCT. Methods and Materials61 patients (7 acute myelogenous leukemia (AML), 33 acute lymphoblastic leukemia (ALL), 18 non-Hodgkin’s lymphoma (NHL), 3 mixed acute leukemia (MAL)) received conditioning radiation treatment with TMLI (8 Gy to bone marrow, 10 Gy to involved field in 2 fractions per day) in conjunction with chemotherapy before transplantation. ResultsThe median age of 61 patients with TMLI was 24 (4–54) years. The prescribed dose covered the entire bone and involved target volume, and the dose of organs at risk (OAR) was reduced by 28%−78% of the prescription dose. Grade 1–2 nausea and vomiting occurred in 12 patients and grade 1–2 pain in 6 patients during radiotherapy. Fatigue occurred in 16 patients. 2 patients had diarrhea, enteritis, and 1 patient had fever. None of patient had grade 3–4 non-hematologic adverse reactions. Late (30 days after HSCT) grade 2 toxicities including reversible enteritis occurred in 3 patients. 5 patients developed infectious pneumonia. The 2 years progression-free survival (PFS) was 64.1% (95% CI: 0.16–0.22) and overall survival (OS) was 74.7% (95% CI: 0.19–0.24) for the 61 patients who had received their planned HSCT. The 2-year non-relapse mortality was significantly reduced to 5% in this patient cohort. ConclusionsThis study demonstrates that hypo-fractionated TMLI (8 Gy to bone marrow, 10 Gy to involved field in a single day) as a conditioning regimen for lymphoma and acute leukemia was feasible and the clinical outcomes were acceptable.

Preliminary Study of Chidamide Combined with Hematopoietic Stem Cell Transplantation in the Treatment of Childhood Acute T-Lymphoblastic Leukemia

To investigate the efficacy and safety of combination chidamide and hematopoietic stem cell transplantation (HSCT) in the treatment of childhood acute T lymphoblastic leukemia (T-ALL). Seven children with acute T lymphoblastic leukemia received hematopoietic stem cell transplantation in SUN Yat-Sen Memorial Hospital of SUN Yat-Sen University were selected. 7 cases of T-ALL were divided into 2 groups: HSCT plus chidamide-treated group (4 cases) and traditional HSCT-treated group (3 cases) as control. The incidence of GVHD and other related complications, as well as implantation, recurrence and survival were compared between the two groups, and the side effects of chidamide were observed. All the patients were follow-up until January 2019. All the 7 patients were alive and, there was no difference in the incidence of acute GVHD between the HSCT plus chidamides treated group and the traditional HSCT-treated group. The implantation rate of HSCT was 100%, and there were no recurrence occurred. During the application of chidamide, 3 cases showed adverse reactions, of which 2 cases had adverse reactions of grade 3 or higher, and 2 cases were hematological adverse reactions (neutropenia, thrombocytopenia), other adverse reactions were non-hematologic adverse reactions (transaminase elevation, fatigue, nausea, vomiting), there were no serious adverse reactions occurred. In the HSCT plus chidamide-treated group, 2 cases were found that mature lymphocytes were not expressed by tumors, during examing for minimal redidaul disease (MRD). Compared with the immunophenotype and TCR rearrangement at first diagnosis, the results did not support the source of residual T-ALL tumor cells. During the review of MRD, it was found that the abnormal T cells showed an increasing trend, indicating that chidamide might induce leukemia cell differentiation through some pathways. Hematopoietic stem cell transplantation is still an effective method to cure children's T-ALL. In some cases, abnormal T-cell nonclonal amplification occurs during the application of chidamide, and the children with T-ALL can tolerable adverse reactions of chidamide.