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 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 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

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

Aclarubicin ; adverse effects ; therapeutic use ; Adult ; Aged ; Cytarabine ; adverse effects ; therapeutic use ; Drug Combinations ; Female ; Harringtonines ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; mortality ; Treatment Outcome ; Young Adult

We report a case of reversible encephalopathy syndrome in a 16-year-old girl with acute myelogenous leukemia (AML), who is undergoing during consolidation chemotherapy composed of BH-AC (N4-behenoyl-1-beta-D-arabinofuranosyl cytosine) and idarubicin. On the 6th day of chemotherapy, she was in a drowsy state following generalized tonic clonic seizure lasting 20 minutes. MR images revealed extensive cortical and subcortical white matter brain edema. Alertness returned over the 24 hr following by the discontinuation of BH-AC and intravenous administration of diphenylhydantoin, although she complained of intermittent headaches and visual disturbance. She gradually recovered from these symptoms during subsequent 7 days. Previously noted abnormal signal intensities have nearly disappreared on follow-up MRI obtained on the 22nd day after the first seizure. She was discharged without any neurologic sequela. This case suggests that BH-AC, a derivative of cytosine arabinoside (1-beta-D-arabinofuranosylcytosine) could be a cause of reversible encephalopathy syndrome.
Adolescence ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/adverse effects* ; Brain/radiography ; Case Report ; Cytarabine/therapeutic use ; Cytarabine/analogs & derivatives* ; Cytarabine/adverse effects ; Female ; Human ; Leukemia, Myelocytic, Acute/drug therapy ; Leukemia, Myelocytic, Acute/complications* ; Magnetic Resonance Imaging ; Seizures/radiography* ; Seizures/chemically induced

The ESHAP regimen, a combination of the chemotherapeutic drugs etoposide, methylprednisolone (solumedrol), high-dose cytarabine (ara-C), and cisplatin, has been shown to be active against refractory or relapsed non-Hodgkin's lymphoma (NHL) in therapeutic trials. We undertook this study to determine whether this regimen would be effective and tolerable in Korean patients. A total of 40 patients with refractory or relapsed NHL (8 indolent and 32 aggressive) were enrolled in this study. The overall response rate was 70% (95% confidence interval; 59.8-89.7%); 22.5% of patients achieved a complete response and 47.5% a partial response. The median survival duration was 12 months (95% confidence interval; 5.9-18.1 months) and the median duration of progression-free survival was 9 months (95% confidence interval; 1.1-16.9 months). The median survival duration of patients with relapsed NHL was longer than that of patients with refractory lymphoma (15 months vs 4 months, p=0.02). Myelosuppression was the most frequent complication and treatment-related mortality was noted in two patients. These results suggest that the ESHAP regimen is effective in patients with relapsed NHL who have a sensitive disease. The role of ESHAP chemotherapy in discriminating patients who are more likely to benefit from a subsequent transplant should be evaluated in the future.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects ; Bone Marrow/drug effects ; Cisplatin/*administration & dosage/adverse effects ; Cytarabine/*administration & dosage/adverse effects ; Disease-Free Survival ; Drug Tolerance ; Etoposide/*administration & dosage/adverse effects ; Female ; Humans ; Lymphoma, Non-Hodgkin/*drug therapy ; Male ; Methylprednisolone/*administration & dosage/adverse effects ; Middle Aged ; Recurrence ; Retrospective Studies ; Salvage Therapy

Treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML) are now well established as complications of cytotoxic chemotherapy. We experienced a 28-yr-old female patient who developed t-MDS/t-AML with characteristic chromosomal abnormalities including 11q23 chromosomal rearrangement following high-dose chemotherapy with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma. The patient was admitted with bulky abdominal masses of B cell lineage non-Hodgkin's lymphoma. After 2 cycles of systemic chemotherapy of the Vanderbilt regimen, the patient underwent ASCT with high dose chemotherapy of the BEAC regimen. She also received radiation of 48 Gy for the residual periportal lymphadenopathy. The initial cytogenetic analysis of the infused mononuclear cells revealed a normal karyotype. Twenty two months after the ASCT, pancytopenia was noted and her bone marrow aspirate showed dysplastic hemopoiesis with myeloblasts up to 12% of nonerythroid nucleated cells. The patient was diagnosed as t-MDS (refractory anemia with an excess of blasts). Cytogenetic analysis showed complex chromosomal abnormalities including 11q23 rearrangement, which is frequently found in topoisomerase II inhibitor-related hematologic malignancies. Four months later, it was noted that the t-MDS had evolved into an overt t-AML. Cytogenetic analysis showed an evolving pattern with more complex abnormalities. The patient was treated with combination che-motherapy, but her leukemic cells were resistant to the therapy.
Adult ; Antineoplastic Agents, Phytogenic/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; B-Lymphocytes/cytology ; Bone Marrow Cells/pathology ; Carmustine/*adverse effects ; Chromosome Aberrations ; Chromosomes, Human, Pair 11 ; Combined Modality Therapy/adverse effects ; Cyclophosphamide/*adverse effects ; Cytarabine/*adverse effects ; Etoposide/*adverse effects ; Female ; Gene Rearrangement ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Leukemia, Myeloid, Acute/*etiology/genetics ; Lymphoma, Non-Hodgkin/*therapy ; Myelodysplastic Syndromes/*etiology/genetics ; Neoplasms, Second Primary/*etiology ; Pelvis ; Pregnancy ; Pregnancy Complications, Neoplastic/*therapy ; Transplantation, Autologous

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

Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Cytarabine ; adverse effects ; therapeutic use ; Diagnosis, Differential ; Female ; Fever ; blood ; chemically induced ; diagnosis ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; drug therapy ; Teniposide ; therapeutic use