Objective: To analyze the efficacy, safety, and long-term prognosis of intermediate-dose cytarabine (Ara-c) regimen in the treatment of children with refractory risk organ involvement Langerhans cell histiocytosis (LCH). Methods: Clinical data of 17 children with multisystem and risk organ involvement LCH who failed the first-line therapy and were treated with intermediate-dose Ara-c (250 mg/m², twice daily) regimen in the Hematology Center, Beijing Children's Hospital from January 2013 to December 2016 were analyzed retrospectively. In addition to the basic treatment of vindesine and dexamethasone, the patients received two regimens: regimen A: the intermediate-dose Ara-c combined with cladribine and regimen B: the intermediate-dose Ara-c alone. The efficacy, safety and prognosis of the two regimens were analyzed. Results: Among all 17 patients, there were 11 males and 6 females, with the diagnosis age of 2.1 (1.6, 2.7) years. Ten children received regimen A, all of them achieved active disease-better (AD-B) after 8 courses of induction therapy. The disease activity scores (DAS) decreased from 5.5 (3.0, 9.0) to 1.0 (0, 2.3). Seven children received regimen B, and 6 of them achieved AD-B after 8 courses of induction therapy. The DAS decreased from 4.0 (2.0, 4.0) to 1.0 (0, 2.0). The follow-up time was 6.2 (4.9,7.2) and 5.2 (3.7,5.8) years in group A and B. The 5-year overall survival rate was 100.0% in both groups, and the 5-year event free survival rate was (88.9±10.5)% and (85.7±13.2)% in group A and B. Grade 3 or 4 myelosuppression was observed in 8 patients in group A and 2 patients in group B. Conclusions: The intermediate-dose Ara-c regimen (with or without cladribine) is effective and safe for patients with refractory high-risk LCH, with a good long-term prognosis.
Male ; Female ; Child ; Humans ; Cytarabine/adverse effects* ; Cladribine/adverse effects* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Histiocytosis, Langerhans-Cell/drug therapy* ; Prognosis

OBJECTIVE: To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children. METHODS: Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae. RESULTS: Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus. CONCLUSION 2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.
Child ; Cladribine/adverse effects* ; Cytarabine ; Histiocytosis, Langerhans-Cell/drug therapy* ; Humans ; Recurrence ; Retrospective Studies

OBJECTIVE: To establish an optimized model of bone marrow suppression induced by cytarabine (Ara-C) in C57BL/6 mice and preliminarily explore the mechanism of myelosuppression based on the cycle and apoptosis of BMNC. METHODS: C57BL/6 mice were intraperitoneally injected with Ara-C 50, 100 and 200 mg/kg for 7 days, respectively. The survival rate and body weight of C57BL/6 mice were monitored. The number of peripheral blood cells and bone marrow nucleated cells (BMNC) was detected, and the morphology of bone marrow, thymus and spleen were measured on the 7th, 14th and 21st day of the experiment. The cycle and apoptosis of BMNC were also detected by flow cytometry. RESULTS: Ara-C 200 mg/kg caused 46.7% mortality in mice, and other doses had no significant effect on mortality. All doses of Ara-C induced bone marrow suppression in mice, as shown by a decrease in the number of peripheral blood cells (WBC, Neu, RBC, PLT) and BMNC (P<0.05), decrease in bone marrow hyperplasia, accompanied by immunosuppression and compensatory hematopoiesis of the spleen, and the above manifestations and duration were dose-dependent. Among them, the myelosuppression caused by Ara-C 50 mg/kg recovered quickly, and caused by Ara-C 200 mg/kg was too severe. The result of flow cytometry showed that Ara-C could cause S and G₂/m arrest and increased apoptosis in BMNC. CONCLUSION Ara-C can induce myelosuppression in mice with a dose-dependent severity and duration, and the model of myelosuppression with Ara-C 100 mg/kg is more optimized. The mechanism is related to the inhibition of BMNC proliferation and the promotion of apoptosis.
Animals ; Bone Marrow Cells ; Bone Marrow Diseases ; Cytarabine/adverse effects* ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL

To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma.
 Methods: A total of 30 patients identified with recurrent refractory diffuse large B-cell lymphoma were enrolled in this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and adverse reaction were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), and the rates of 1, 2, and 4-year OS and PFS were analyzed. The prognosis was evaluated with univariate analysis.
 Results: The ORR was 56.7% and clinical benefit rate (CBR) was 83.3% after 2 cycles. Five patients achieved complete remission, 12 achieved partial remission, and 8 achieved stable disease. The median OS was 22 (1.5-140) months. The 1, 2, and 4-year OS rates were 59.1%, 48.2%, and 40.2%, respectively. The median PFS was 14 (1.5-140) months. The 1, 2 and 4-year PFS rates were 56.3%, 42.2%, and 31.7%, respectively. The main adverse reaction was myelosuppression. Three patients suffered from grade III-IV leukopenia and 1 thrombocytopenia. Grade I-II gastrointestinal toxicity was 20%. No heart, liver, and kidney damages at grade III-IV were observed.
 Conclusion: The NAPD regimen is effective and its toxicity is well tolerated for the treatment of recurrent refractory diffuse large B-cell lymphoma. It is a salvage chemotherapy regimen worth to be verified.
Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; Cytarabine ; administration & dosage ; Dexamethasone ; administration & dosage ; Humans ; Induction Chemotherapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; mortality ; Neoplasm Recurrence, Local ; drug therapy ; mortality ; Retrospective Studies ; Salvage Therapy ; methods ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives ; Vinorelbine

BACKGROUND: The present study describes our 10-year experience with uveoretinal adverse events that manifest because of chemotherapy. METHODS: A retrospective chart review was performed for all patients who presented to the ophthalmologic department while undergoing systemic chemotherapy between July 2005 and June 2015. RESULTS: A total of 55 patients (mean age, 51.2 years, 38 women [69.1%]) suspected of having uveoretinal disease owing to the use of chemotherapeutic agents alone were enrolled. Breast cancer was the predominant disease (36.4%); noninfectious anterior uveitis (21.8%) was the most common condition. Bilateral involvement was observed in 16 patients (29.1%). Although cisplatin (21.8%) was the most commonly used drug, daunorubicin, cytarabine, tamoxifen, toremifene, and imatinib were also frequently used. The median duration until ophthalmologic diagnosis was 208.5 days (range, 19–5,945 days). The proportion of patients with final visual acuity (VA) < 20/40 Snellen VA (0.5 decimal VA) was 32.7%. However, no relationship was observed between final VA < 20/40 and age, sex, therapeutic agents, and metastasis. CONCLUSION: Uveoretinal complications were mostly mild to moderate and exhibited a favorable response to conservative therapy. A considerable number of patients exhibited significant irreversible loss of vision after cessation of the causative chemotherapeutic agent. Ophthalmological monitoring is required during chemotherapy.
Antineoplastic Agents ; Breast Neoplasms ; Cisplatin ; Cytarabine ; Daunorubicin ; Diagnosis ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Imatinib Mesylate ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Retrospective Studies ; Tamoxifen ; Toremifene ; Uveitis ; Uveitis, Anterior ; Visual Acuity

BACKGROUND: A number of anticancer agents are known to induce many adverse reactions in the skin. Related cutaneous adverse drug reactions influence the morbidity, mortality, and anti-cancer regimen of the patients. A multidisciplinary approach to cancer management has been emphasized. OBJECTIVE: To identify the causative anticancer agents and frequency of adverse reactions in the skin. METHODS: We retrospectively reviewed the medical records of patients who consulted at the Dermatology Department of Busan Paik Hospital and Haeundae Paik Hospital from January 2013 to February 2015. RESULTS: A total of 140 patients were enrolled. Among the 45 patients treated with antimetabolite analogs (30 cytarabine, 7 gemcitabine, 3 methotrexate, 2 fludarabine, 2 doxifluridine, and 1 decitabine), exanthematous drug eruption (49.1%) was the most common reaction, followed by hand-foot syndrome (28.3%). Among the 35 patients treated with fluorouracil (22 5-fluorouracil and 13 capecitabine), hand-foot syndrome (47.2%) was the most common, followed by acneiform eruption (25.0%). Among the 24 patients treated with epidermal grow factor receptor inhibitors (10 erlotinib, 10 cetuximab, and 4 gefitinib), acneiform eruption (54.8%) was the most common, followed by xerosis (19.4%). Among the 11 patients treated with anthracyclines (9 doxorubicin, 1 daunorubicin, and 1 idarubicin), acneiform eruption (45.5%) was the most common, followed by hand-foot syndrome (36.4%). Among the 7 patients treated with taxanes (4 docetaxel and 3 paclitaxel), hand-foot syndrome (42.8%) was the most common. Among the 6 patients treated with angiogenesis-inducing inhibitors (3 sorafenib, 2 pazopanib, and 1 sunitinib), hand-foot skin reaction (66.7%) was the most common. Only 2 patients (1.4%) changed treatments due to intolerable skin reactions. CONCLUSION: Clinicians should be aware of the various skin reactions of anticancer agents and predict their clinical course effectively.
Acneiform Eruptions ; Anthracyclines ; Antineoplastic Agents ; Busan ; Cetuximab ; Cytarabine ; Daunorubicin ; Dermatology ; Doxorubicin ; Drug Eruptions ; Drug-Related Side Effects and Adverse Reactions ; Erlotinib Hydrochloride ; Fluorouracil ; Hand-Foot Syndrome ; Humans ; Medical Records ; Methotrexate ; Mortality ; Retrospective Studies* ; Skin ; Taxoids

The aim of this study was to investigate effects of IAT and MAT chemotherapeutic regimens treating patients with refractory and relapsed acute myeloid leukemia (AML). 99 patients with refractory and relapsed AML received IAT regimen or MAT regimen as study objects were retrospectively analyzed (56 patients with refractory AML and 43 patients with relapsed AML). Among of them, 28 patients were treated with IAT regimen, and 71 patients received with MAT regimen. The results showed that in 2 groups mentioned above the OR was 65.7%, CR was 49.5%, PR was 16.2%; in IAT group the OR was 64.3%, CR was 46.4%; in MAT group the OR was 66.2%, CR was 50.7%, no statistical difference was found between these 2 groups; The 2 years overall survival was 25% in IAT group and 15.5% in MAT group. Serious infection in IAT and MAT regime groups was 25% and 9.9%, respectively. It is concluded that both IAT and MAT regimens are effective methods for inducing CR in patients with refractory of relapsed AML. IAT and MAT regimens can be used in treatment of the refractory or relapsed MAL patients who were not respond to other regimen.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child ; Cytarabine ; administration & dosage ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; etiology ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Vidarabine ; administration & dosage ; Young Adult

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; adverse effects ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Mitoxantrone ; administration & dosage ; adverse effects ; Young Adult

This study was aimed to investigate the protective effect of Wit3a gene modification on mouse bone marrow mesenchymal stem cells against the injury induced by Ara-C. The gene-modified MSC steadily expressing Wnt3a were established by adenovirus system. The acute direct damage effects of different concentrations of Ara-C on the unmodified MSC and the gene-modified MSC were assessed by using an in vitro culture system, and the corresponding controls were set. The proliferation and apoptosis of MSC exposed to Ara-C were detected by cell count kit-8 (CCK-8) and flow cytometry. The expression of BCL-2 protein related with cell apoptosis was assayed by Western blot. The results indicated that as compared with unmodified MSC, Ara-C exhibited a less inhibitory effect on the proliferation of gene-modified MSC. There was obvious difference between unmodified MSC and gene-modified MSC (p < 0.05). The proliferation of gene-modified MSC began to recover at 72 hours after removal of Ara-C. However, unmodified MSC showed sustained suppression of proliferation after withdrawal of Ara-C. In apoptosis, the apoptosis rate of gene-modified MSC induced by Ara-C was significantly lower than those of unmodified MSC (p < 0.05). In addition, the expression levels of BCL-2 protein in gene-modified MSC were up-regulated compared with unmodified MSC (p < 0.05). It is concluded that Wnt3a gene modification can significantly mitigate the damage of mouse bone marrow MSC induced by Ara-C.
Animals ; Bone Marrow Cells ; drug effects ; metabolism ; Cytarabine ; adverse effects ; Mesenchymal Stromal Cells ; drug effects ; metabolism ; Mice ; Organisms, Genetically Modified ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; Wnt3A Protein ; genetics

OBJECTIVETo assess the efficacy and toxicity of the kangai injection combination of fludarabine (Flud), cytosine arabinoside (Ara-C), and granulocyte colony-stimulating factor (G-CSF) (FLAG) in refractory/relapsed acute leukemia (AL) patients.

METHODFrom 2004 to 2010 in our hospital, the 49 cases of refractory/relapsed acute luekemia were randomly divided into treatment group (28 cases) and control group (21 cases). The control group were treated by kangai injection plus FLAG regimen, and the control group were treated by FLAG regimen.

RESULTThe remission rate of treatment and total effective rate treatment group were 57.1% (16/28) and 71.4% (21/28), the control group were 52.3% (11/21) and 61.9% (13/21), there were no significant differences in the two groups. Duration of neutrophils less than 0.5 x 10(9)/L in treatment group was (14 +/- 6) day, control group was (23 +/- 3) day, Duration of platelet less than 25 x 10(9)/L in treatment group was (17 +/- 6) day, control group was (31 +/- 2) day, treatment group of III-IV degree of infection was 6.9% (1/28) and control group was 23.8% (5/21) between the two groups were significantly different (P < 0.05). treatment group of III- IV degree of gastrointestinal; toxicity was 10.7% (3/28) and control group was 28. 5% (6/ 21).

CONCLUSIONKangai injection plus FLAG regimen could increase the remission rate, shorten the period of bone marrow suppression, significantly reduced the incidence and degree of infection, play a important role in attenuated efficiency.

Acute Disease ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; Cytarabine ; administration & dosage ; adverse effects ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; adverse effects ; Humans ; Injections ; Leukemia ; drug therapy ; Male ; Middle Aged ; Vidarabine ; administration & dosage ; adverse effects ; analogs & derivatives