A retrospective analysis of the efficacy and safety of imatinib in children with chronic myeloid leukemia during chronic phase / 中华儿科杂志

Objective@#To evaluate the efficacy and safety of imatinib in the treatment of newly diagnosed chronic myeloid leukemia during chronic phase (CML-CP) in children and to analyze the difference of the efficacy and safety between imported original imatinib (Gleevec) and domestic generic imatinib (Xinwei).@*Methods@#Clinical data of 35 children with newly diagnosed CML-CP in Beijing Children′s Hospital from January 2014 to January 2018 were collected, among which 15 cases were treated with the imported original imatinib (original drug group) and 20 cases were treated with the domestic generic imatinib (generic drug group). The hematological, cytogenetic and molecular reactions and safety of the treatments were monitored at months 3, 6 and 12. Chi square test or rank sum test was used for the comparison between two groups.@*Results@#A total of 35 cases were treated for over 3 months, 31 cases were treated for over 6 months and 25 cases were treated for over 12 months. At 3 months, main cytogenetic response was obtained in 15 (100%) cases in the original drug group and 16 (80%) cases in the generic drug group respectively (χ2=3.387, P=0.119). At 6 months, complete cytogenetic response was obtained in 12 (80%) cases in the original drug group and 10 (63%) cases in the generic drug group (χ2=1.435, P=0.390). At 12 months, BCR-ABLIS ≤ 0.1% was obtained in 11 (92%) cases in the original drug group and 10 (77%) cases in the generic drug group (χ2=1.009, P=0.593). There was no significant difference at all stages (all P>0.05). Hematologic toxicity occurred in 7(20%) cases. The non-hematologic adverse reactions include nausea in 8 (23%) cases, pain in 8 (23%) cases, edema in 6 (17%) cases, emesis in 2 (6%) cases, fever in 2 (6%) cases, weakness in 1 (3%) case, rash in 1 (3%) case. The adverse reactions were easy to control and no drug toxicity related deaths occurred. There was no significant difference in the adverse reactions between original drug group and generic drug group (P>0.05).@*Conclusions@#Imatinib had a good efficacy and safety in the early treatment of newly diagnosed CML-CP in children. The efficacy and safety of generic imatinib is similar to that of imported imatinib.

Allogeneic hematopoietic stem cell transplantation-associated thrombotic microangiopathy:9 cases report of children and literature review / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics,treatment and prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT)-associated thrombotic microangiopathy (TA-TMA) in children.Methods The clinical information,treatment and prognosis of 9 cases with TA-TMA hospitalized following alloHSCT from January 2008 to November 2017 in Hematology Oncology Center,Beijing Children's Hospital,Capital Medical University were retrospectively analyzed.Results Of all the 283 allo-HSCT recipients,9 patients (3.2％) were diagnosed as TA-TMA.Among them,there were 5 male and 4 female,with a median age of 94 months (39-129 months).The median time to of diagnosis was 63 days (6-342 days) after HSCT.Additionally,the median platelet counts,hemoglobin and lactate dehydrogenase(LDH) levels were 44 × 109/L [(7-75) × 109/L],76 g/L (40-105 g/L) and 594 U/L(445-1 386 U/L).Neurological symptoms were found in 5 of the patients,4 had kidney involvement,and 6 had gastrointestinal involvement.The major treatment of TA-TMA was plasma exchange,Rituximab and defibrotide instead of the use of calcineurin inhibitors.Finally,4 patients achieved response after treatment,5 children died of ineffective treatment.Conclusion TA-TMA is a fatal complication after allo-HSCT.It can lead to multiorgan and multi-systems dysfunction.If there are more than 2 systems involved in TA-TMA,it suggests poor prognosis.The combined therapy is better than monotherapy,and the selective individual treatment of TA-TMA is essential.

Effect of nutritional support on therapy-related side effects in acute lymphoblastic leukemia children undergoing chemotherapy / 中华实用儿科临床杂志

Objective To analyze the changes in nutritional status changes of pediatric acute lymphoblastic leukemia (ALL) patients before and after chemotherapy and to evaluate the effects of enteral nutritional support on the states of nutrition and complication of chemotherapy.Methods Sixty-two newly diagnosed ALL patients from Novem-ber 2012 to December 2013 in Center of Hematology,Beijing Children's Hospital Affiliated to Capital Medical University were enrolled in this study.Patients were randomly assigned into an intervention group and a control group.During the induction and the early consolidation chemotherapy,the control group was given routine low fat diet routinely,and the intervention group was given Nestle peptamen [20 mL/(kg · d)] as the enteral nutritional support,meanwhile the routine low fat diet was also given.Changes in the nutritional status before and after chemotherapy and effectiveness of nutritional complementary therapy for preventing the chemotherapy complications were analyzed.Results (1) Basic information:there was no significant difference in age,gender,risk group,anthropometry,albumin and pre-albumin level between 2 groups before chemotherapy.(2)Nutritional status:the rate of malnutrition was 11.3 ％,and skinniness cases under 5 years of age occupied 10.0％.In the control group,the Z scores of W/H (weight-for-length/height,t =3.160,P =0.040),the Z scores of BMI (body mass index,t =3.490,P =0.010) and the albumin level(t =-1.805,P ＜0.001) decreased after chemotherapy,and the difference was statistically significant.On the other hand,the Z scores of W/H and BMI kept stable after chemotherapy in the intervention group,the albumin level raised from (40.53 ±3.96) g/L to (44.36 ± 3.31) g/L (t =-4.500,P ＜ 0.001) and the pre-albumin level raised from (126.55 ± 39.28) g/L to (189.55 ± 51.81) g/L(t =2.710,P =0.010),which was of statistical difference.The albumin level(t =5.020,P ＜ 0.001),pre-albumin level (t =3.036,P =0.040) and the Z scores of W/H (t =2.790,P =0.010),BMI (t =3.370,P ＜ 0.001),weight for age (W/A,t =2.830,P =0.010) were all higher in the intervention group,and the differences in statistical significance were found.(3)Side effects of chemotherapy:patients in the intervention group had higher hemoglobin (t =2.070,P =0.043) and platelet (Z =-2.19,P =0.033) level during the chemotherapy which induce less platelet [(0.50 ± 1.00) U vs (2.00 ± 2.00) U ; Z =-3.53,P =0.003] and red blood cells [(3.87 ± 2.01) U vs (5.25 ± 1.87) U ;t =-2.810,P =0.007] transfusion.Period of neutrophil deficiency [(15.67 ± 8.85)d vs (25.94 ±8.72) d;t =-4.601,P ＜0.001]was also shorter than that in the control group.Other complications had no difference between two groups exclude mild liver function abnormality was found more in the controls(x2 =6.680,P =0.010).(4)Safety:the complete remission rate 15 days after chemotherapy was 83.3％ in the intervention group and 81.2％ in the control group (x2 =0.046,P =0.830).All patients got complete remission on day 33.There was no significant difference.No pancreatitis happened in both groups during the chemotherapy.Conclusions Malnutrition rate is high among newly diagnosed ALL pediatric patients,and the nutritional status will deteriorate during the chemotherapy.Enteral nutritional support contributes to maintaining the stability of nutritional status.Enteral nutritional support improves the tolerance of hematopoietic system to chemotherapy.The effect for other complications remains to be confirmed by more extensive study in future.Nestle peptamenas enteral nutritional support productions are safe for ALL patients undergoing chemotherapy.

Changes of angiopoietin 1 expression in G-CSF induced hematopoietic stem progenitor cells mobilization / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the changes and mechanism of angiopoietin1 (Ang1) in murine bone marrow during G-CSF induced mobilization of hematopoietic stem/progenitor cell.</p><p><b>METHODS</b>The proportion of Lin-Sca1⁺cKit⁺ (LSK) cells in peripheral blood of C57BL/6 mice before and after G-CSF mobilization was detected by flow cytometry. Expression changes of Ang1 and osteocalcin (OCN) during HSC mobilization were determined by immunohistochemistry, enzyme linked immunosorbent assay (ELISA) and real-time fluorescence quantitative PCR. The number of osteoblasts in the bone marrow was counted under the microscope.</p><p><b>RESULTS</b>After treated with G-CSF, the proportion of LSK cells in peripheral blood significantly increased from the controls (0.04 ± 0.01)% to (0.61 ± 0.05)% at day 5 (P<0.05). Before G-CSF mobilization, the endosteum cells expressed higher level of OCN and Ang1 than that of bone marrow nucleated cells. The mRNA expression level of OCN was significantly reduced from 28.64 ± 8.61 in the controls to 12.55 ± 7.06 on day 3 and 4.75 ± 1.62 on day 5, and the expression level of Ang1 also declined from 2.84 ± 0.95 in the controls to 0.93 ± 0.30 on day 3 and to 0.92 ± 0.22 on day 5 after G-CSF mobilization. The number of endosteum osteoblasts was significantly decreased after mobilization (P<0.05). The Ang1 expression was decreased in the BM after mobilization. The serum OCN was significantly reduced from (24.11 ± 3.17) ng/ml in the controls to (9.96 ± 2.16) ng/ml on day 3 and (8.43 ± 2.62) ng/ml on day 5, and the Ang1 also declined from (2.24 ± 0.52) ng/ml in the controls to (1.21±0.38) ng/ml on day 3 and (0.90±0.24) ng/ml on day 5.</p><p><b>CONCLUSION</b>In G-CSFinduced HSPC mobilization, the bone marrow osteoblasts retraction causes reduction of Ang1, and the reduction of Ang1 may contribute to HSPC mobilization.</p>

Efficacy of bisphosphonates in reducing skeletal events in patients with multiple myeloma / 白血病·淋巴瘤

Objective To review the efficacy of bisphosphonates in reducing skeletal events in patients with multiple myeloma. Methods Two hundred and five patients with newly diagnosed MM were enrolled in this retrospective study,with bisphosphonates or not.Skeletal-related events,therapeutic reaction of myeloma bone disease and patient survival were analyzed. Results The occurrence of skeletal-related events (SRE) per patient year (P＜0.01) and the time to first SRE (P＜0.05)were significantly lower in the reatment group than in the untreated group. After 6 cycles of treatment, a significant higher percentage of effective and marked effect patients were observed through X ray in the treatment group (80.0 ％) compared to the untreated group (48.7 ％), P＜0.001. There was no overall significant difference in the level of serum calcium between the two groups (P=0.278). After 6 cycles of treatment, the patients who received bisphosphonates had significant decreases in bone pain and lower ECOG score (ECOG≤2) compared to the untreated group (P＜0.05). Bisphosphonates were tolerated well, and the common adverse reaction including gastrointestinal reaction (3 cases,3.3 ％),fever (lcase,1.1％) and skin rash (2 cases,2.2 ％).There was no significant difference in overall survival between the two treatment groups,(P=0.580).Conclusion Infusions of Bisphosphonates could reduce the occurrence of skeletal- related events (SRE), prolong the time to first SRE and improve the quality of life of patients with multiple myeloma. Bisphosphonates could not prolong survival time of myeloma patients.