Clinical and molecular characteristics and prognosis of classical hairy cell leukemia and hairy cell leukemia variant / 中华内科杂志

Objective: To evaluate the clinical characteristics, treatment response, and outcomes in patients with classical hairy cell leukemia (cHCL) and HCL variant (HCL-V). Methods: This is a retrospective case series study. Between January 2011 and December 2021, clinical data of 30 patients newly with diagnosed HCL at Peking Union Medical College Hospital were analyzed. The main outcome measures include clinical characteristics, treatment efficacy and survival. The Kaplan-Meier method was used for survival analysis. Results: Twenty-one cases of cHCL and 9 cases of HCL-v were included. The median age at diagnosis was 55.5 (range, 30-86) years, with the ratio of male to female 2.75∶1. The main clinical manifestations included fatigue in 11 cases (36.7%), abdominal distension in 7 cases (23.3%), and infection in 4 cases, while 8 cases were asymptomatic. Splenomegaly was reported in 24 cases (80.0%), including 7 (23.3%) with megalosplenia. The white blood cell count, lymphocyte count, and the proportion of peripheral hairy cells in HCL-v group were significantly higher than those in cHCL group, whereas the development of anemia, thrombocytopenia, and monocytopenia in cHCL group was more remarkable than that in HCL-v group (all P<0.05). The BRAF-V600E gene mutation was detected only in cHCL patients (11/14 vs. 0/9, P<0.001). In terms of immunophenotype, the expression of CD25, CD103, CD123 and CD200 in cHCL group (20/20, 20/20, 4/7, 7/17) were all stronger than those in HCL-v group (3/9, 7/9, 0/4, 2/8). Twenty-two patients were treated, of which 13 cases (12 cases of cHCL and 1 case of HCL-v) with cladribine, and 9 cases (4 cHCL and 5 HCL-v) with interferon. Complete remission rate and overall response rate were comparable between cladribine and interferon treatment groups (both P<0.05). The median follow-up time was 31 (range, 1-125) months, and the median overall survival (OS) of the entire group was 125 months. The 5-year OS rate in HCL-v patients represented a trend of inferior (50.0% vs. 95.0%, P=0.207). Conclusions: The clinical features of HCL are unspecific, which includes fatigue, splenomegaly and recurrent infection. The clinical features, immunophenotype, treatment response and prognosis of HCL-v are different from those of cHCL. BRAF-V600E gene mutation is suggested as a key marker for differential diagnosis. Cladribine is recommended as front-line regimen of cHCL patients with satisfactory efficacy and prognosis. Conversely, response and clinical outcome in HCL-v patients still need to be improved.

Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Hairy cell Leukemia in a Filipino male during the COVID-19 pandemic – report of a rare case

@#Hairy cell leukemia (HCL) is a rare, chronic, mature B-cell lymphoproliferative disorder accounting for 2% of all leukemias. In this paper, we would like to present our experience in the management of HCL in a financially limited setting where other diagnostic tests and chemotherapy are unavailable. The case report aims to emphasize the recognition of the distinctive morphology of hairy cells in the peripheral blood in the consideration of the initial diagnosis. A 60-year-old Filipino male was incidentally found to have anemia, thrombocytopenia and an absolute neutrophilic count below 1,000 in a pre-operative clearance for elective herniorrhaphy. Blood smear revealed atypical lymphocytes with hair like cytoplasmic projections. CT-scan of the abdomen showed splenomegaly and prominent paraaortic nodes. Flow cytometry of the bone marrow aspirate was consistent with an involvement of a Mature B cell neoplasm markers CD19, CD20, CD22 and surface immunoglobulin lambda and hairy cell leukemia markers CD11c, CD103 and CD25. He responded to six-weekly sessions of Cladribine with remission of the bone marrow and hematologic parameters. HCL is a rare type of a mature B cell neoplasm characterized by pancytopenia, splenomegaly, bone marrow fibrosis and the presence of atypical lymphoid cells with hairy projections in blood, bone marrow and spleen. Immunophenotyping express CD11c, CD103, CD123, and CD25. BRAF V600E mutation is the disease defining genetic event. Cladribine and Pentostatin are the first line of treatment. Cases of leukemia can be easily overlooked because of the mild derangement in the complete blood count. A meticulous differential review of the atypical lymphocyte, is the first step in the diagnosis of this rare disease.

Recurrent and Refractory Langerhans Cell Histiocytosis in Children Treated with the Combination of Cladribine and Cytarabine / 中国实验血液学杂志

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.

Efficacy and Safety of Cladribine-based Intensified Conditioning Regimen in Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen.@*METHODS@#The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed.@*RESULTS@#The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients.@*CONCLUSION@#The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.

CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML).@*METHODS@#Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M@*RESULTS@#Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M@*CONCLUSION@#The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.

Outcome of hairy cell leukemia patients treated with cladribine - a 10-year single-center experience in Pakistan

ABSTRACT Introduction and objective: Hairy cell leukemia is an uncommon, indolent B-cell lymphoproliferative disorder. Therapy with cladribine (2-chlorodeoxyadenosine) is able to induce complete remission (CR) in the majority of patients after a single course of treatment. We report the outcomes of patients treated at Aga Khan University Hospital, Karachi, Pakistan. Methods: This was a retrospective review. Medical records of patients were used to collect data. Results: A total of 21 patients with hairy cell leukemia were treated with cladribine. All patients achieved an initial CR. Four patients (19%) required hospitalization and therapy for neutropenic fever. Six patients (29%) relapsed at a median of 48 months. All 6 patients were treated for relapse, out of which 4 achieved CR, 1 had partial response and 1 had refractory disease. The overall survival rate was 90.5%, with a median follow-up of 35 months. Conclusion: A single course of cladribine is able to induce CR in a vast majority of patients. Unfortunately, relapse is not uncommon. Patients who relapse can be successfully retreated with cladribine. Cladribine has impressive efficacy and a favorable acute and long-term toxicity profile when administered to patients with HCL.

A Case of Recurrent Rosai-Dorfman Disease Successfully Treated with 2-Chlorodeoxyadenosine (Cladribine) / 임상소아혈액종양

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is a rare histiocytic disorder of unknown etiology. Most patients with RDD have spontaneous remission, but in some patients, the disease recurs after complete remission and may not respond to general treatment. Some patients with RDD involving the extranodal system can have serious symptoms such as vital organ dysfunction due to mass effects, neurological symptoms caused by intracranial involvement, and respiratory distress with airway involvement. We report the case of a 7-year-old girl with severe dyspnea due to refractory extranodal RDD that caused progressive upper airway obstruction. She was admitted because of nasal congestion and persistent cervical lymphadenopathy, and diagnosed as having RDD by cervical lymph node incisional biopsy. The initial prednisone treatment did not improve her symptoms. The following contrast-enhanced neck computed tomography revealed a newly developed airway mass protruding in the upper trachea. After 8 weeks of chemotherapy with vinblastine, methotrexate, and prednisone, complete remission was attained. Seven months after chemotherapy cessation, the disease recurred, and chemotherapy with vincristine, cytarabine, and prednisone was resumed. Despite the chemotherapy and emergency radiotherapy, no improvement was observed in the cervical lymph node enlargement and airway obstructive symptom due to the upper tracheal mass. 2-Chlorodeoxyadenosine (cladribine) therapy was initiated, and the patient got complete remission after 6 cycles of the cladribine treatment and maintained no evidence of disease for 2 years. We suggest that cladribine is an effective treatment option for recurrent/refractory RDD.

Fludarabine and Rituximab in Relapsed or Refractory Hairy Cell Leukmia Variant: A Case Report and Review of Literature / 고신대학교의과대학학술지

Hairy cell leukemia (HCL) is a rare chronic B cell leukemia morphologically characterized by cells with an abundant cytoplasm and hair-like projections that can be found in the peripheral blood and bone marrow. The treatment for HCL is splenectomy or chemotherapy with the purine analogs pentostatin and cladribine. However, patients continue to relapse. Retreatment with the same or alternate purine analogs produces lower response rates and a shorter duration of response. Fludarabine is another purine analog widely used in treating indolent lymphoid cancers, often in combination with rituximab. Here, we report a case of HCL variant in a 60-year-old man who experienced multiple relapses after splenectomy and retreatment with cladribine. The patient was then treated with fludarabine and rituximab combination chemotherapy. After the treatment, he achieved complete remission that continued for 35 months.

Eficacia y seguridad de cladribina en el tratamiento de pacientes con diagnóstico de tricoleucemia / Efficacy and safety of cladribine in the treatment of patients diagnosed with tricholeukemia

INTRODUCCIÓN: Antecedentes: En el present dictamen preliminar expone la evaluación de tecnología de la eficacia y seguridad del uso de cladribina en el tratamiento de pacientes adultos con diagnostico de leucemia de células vellosas o tricoleucemia. Así, los médicos hematólogos. Aspectos Generaels: La leucemia de células vellosas o tricoleucemia es una neoplasia de los linfocitos B pequeños que se caracteriza por la presencia de "células peludas" o células con núcleos ovales indentados y citoplasma abundante con proyecciones citoplasmáticas "pelulas", obervables en el 90% de los pacientes que se padecen. Los marcadores más comunes expresados por las células peludas son el CD19, CD20 y CD22, con una notable co-expressión de CD103, CD25, CD11c. Tecnologia Sanitaria de Interés: Cladribina es un agente antineoplásico sintético que se encuentra disponbile en viales para infusión endovenosa continua. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de cladribina en el tratamiento de pacientes con tricoleucemia en las bases de datos de Medline, Embase, Scopus, Web of Science, Cinahl, Cochrane y Tripdatabase. RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de la evidencia que sustente el uso de cladribina en el tratamiento de la tricoleucemia según la pregunta PICO establecida. CONCLUSIONES: Rituximab ha sido empleado en EsSalud como primera linea de tratamiento frente a la falta de acceso a cladribina. Sin embargo, ciertos pacientes presentan respuesta inadecuada o intolerancia a rituximab y requieren otras alternativas de tratamiento. Adicionalmente, se ha solicitado el uso de cladribina como terapia de primera línea en pacientes con tricoleucemia dado que en la actualidad se emplea un medicamento que no se encuentra indicado como primera líena para lla condición. En base a esta solicitud se llevó a cabo una rewvisión de la literatura sobre la eficacia y seguridad de cladribina en la poblaciones de pacientes previamente tratados y no-tratados. El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI aprueba el uso de cladribina como alternativa de tratamiento en pacientes con tricoleucemia previamente tratados o como primera línea de tratamiento. El perído de vigencia del presente dictamen preliminar es de dos años y la continuación de dicha aprobación estará sujeta a los resultados obtenidos de los pacientes que se beneficien con dicho tratamiento y a nueva evidencia que pueda surgir en el tiempo.

Effectiveness of CLAT Protocol for Treating Patients with Refractory Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical efficacy and toxicity of CLAT protocol (cladribine, cytarabine and topotecan) for treating patients with refractory acute myeloid leukemia (R-AML).</p><p><b>METHODS</b>A total of 18 patients with R-AML (median age 37 years, range 18 to 58 years; male n = 16, female n = 2) were treated with CLAT protocol, which consisted of cladribine 5 mg/m(2)/d, i.v. on days 1-5, cytarabine 1.5 g/m(2)/d, i.v. on days 1-5, topotecan 1.25 mg/m(2)/d, i.v. on days 1-5 and G-CSF 300 µg/d subcutaneous injection on day 6 until neutrophile granulocyte recovery.</p><p><b>RESULTS</b>Out of 18 patients 2 died of severe infection before the assessment. Among 16 evaluated patients, 10 (55.6%) achieved complete remission (CR), and 2 (11.1%) achieved partial remission (PR), the overall response rate was 66.7%, the rest 4 patients did not respond (NR). The median overall survival time and DFS for the CR patients was 9.5 months (95%CI: 6.7-16.64) and 9.5 months (95%CI: 6.1-16.7) respectively. The 1 year OS and DFS rates were 45% and 46.9%, respectively. All patients developed grade 4 of granulocytopenia and thrombocytopenia, the median duration was 13 (range 2 to 21) days and 12 days (range 2 to 21), respectively, all patients developed infection, 2 patients died of severe infection. The most common non-hematological side effects included nausea, vomiting, diarrhoea, rash, aminotransferase or bilirubin elevation and were grade 1 to 2.</p><p><b>CONCLUSION</b>The CLAT protocol seems to have promising for the treatment of refractory AML patients, and patients well tolerated. This CLAT protocol offers an alternative treatment for R-AML patients who received severe intensive treatment, especially with anthracycline-containing chemotherapy.</p>

Cladribine treatment of repeatedly-relapsed Langerhans cell histiocytosis: a case report and literature review / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the salvage therapy for a child with refractory and ( or) repeatedly-relapsed Langerhans cell histiocytosis.</p><p><b>METHOD</b>Data of a patient with Langerhans cell histiocytosis whose disease relapsed repeatedly treated with cladribine was collected and analyzed and the related literature was reviewed.</p><p><b>RESULT</b>The initial symptoms developed 3 months after his birth, multiple systems (skin, skeleton, lung, liver) were involved; he was sequentially treated with LCH-III-Group I, JLSG-96, DAL-HX90 chemotherapeutic regimens. The patient got relapses for more than 3 times, but the disease got completely controlled after being treated with cladribine when the patient was 6 years old. The dosage was 10 mg/(m2 · d) for 4 days, and one course lasted for 28 days, the third to fifth courses of treatment used Arac in combination, the whole treating time lasted for 5 months. The patient remained in persistent remission for 8 months since discontinuation of treatment. "Langerhans cell histiocytosis" "refractory" "cladribine" were used as the key words to search in the data bases CNKI, Wanfangdata and Pubmed, 11 articles were picked. According to the literature, the effective rate of cladribine in treatment of repeatedly relapsing Langerhans cell histiocytosis was 44%-100%, with a good response of 22%-86%, the dose was 5-13 mg/(m2 · d). The main side effects were hematological system damages and infection.</p><p><b>CONCLUSION</b>The effect of commonly used chemotherapeutic regimens is limited for children with refractory and (or) repeatedly-relapsed Langerhans cell histiocytosis and cladribine can be used as an alternative therapeutic option of the salvage therapy.</p>

Oral Disease-Modifying Therapies for Multiple Sclerosis

Classical multiple sclerosis (MS) treatments using first-line injectable drugs, although widely applied, remain a major concern in terms of therapeutic adherence and efficacy. New oral drugs recently approved for MS treatment represent significant advances in therapy. The oral route of administration clearly promotes patient satisfaction and increases therapeutic compliance. However, these drugs may also have safety and tolerability issues, and a thorough analysis of the risks and benefits is required. Three oral drugs have been approved by regulatory agencies for MS treatment: fingolimod, teriflunomide, and dimethyl fumarate. This article reviews the mechanisms of action, safety, and efficacy of these drugs and two other drugs that have yielded positive results in phase III trials: cladribine and laquinimod.

Complete recovery of pyoderma gangrenosum after successful treatment of underlying hairy cell leukemia with cladribine

No abstract available.

Mechanisms of cladribine-inducing apoptosis of multiple myeloma RPMI 8226 cells in vitro / 中国实验血液学杂志

This study was purposed to explore the mechanisms of cladribine (2-CdA)-inducing apoptosis of multiple mycloma RPMI 8226 cells. The MTT method was used to determine cell proliferation after being treated with 2-CdA. Apoptosis and cell cycle progression were examined by flow cytometry. Transmission electron microscopy was used to observe ultrastructural changes of RPMI 8226 cells. RT-PCR and Western blot were used to analyze the mRNA and protein expression levels of BCL-2, MCL-2 and caspase-3 respectively. The results showed that the 2-CdA inhibited proliferation of RPMI 8226 cells in time and dose-dependent manner. Typical apoptotic morphological and ultrastructure changes could be observed by electron microscopy. Flow cytometry showed that 2-CdA induced myeloma cell apoptosis and arrested myeloma cells in the G2/M phase. The mRNA expression of BCL-2 and MCL-1 decreased but that of caspase-3 not apparently changed. Western blot results suggested that the change trend of BCL-2 MCL-1 and caspase-3 was the same as result of RT-PCR. It is concluded that 2-CdA exhibits inhibitory effects on RPMI 8226 cells in vitro. Activating the mitochondrial and death receptor pathways of apoptosia may be the potential mechanism, meanwhile, the cell cycle arrest may also play a critical role in apoptosis.

Cladribine for 13 cases refractory high-risk children Langerhans cell histiocytosis / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the efficacy and adverse reaction of the improvement program of cladribine combined with cytarabine (2-CdA+Ara-C) in treatment of children with refractory high-risk Langerhans cell histiocytosis (LCH).</p><p><b>METHODS</b>13 patients with refractory high-risk LCH or recurrent LCH were treated by combined 2-CdA+Ara-C chemotherapy. The treatment efficacy and the disease state in the process were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009). The drug toxicity was evaluated according to the Common Terminology Criteria Adverse Events Version 4.0 (CTCAE v4.0, 2009).</p><p><b>RESULTS</b>Of 13 patients, 10 cases achieved non active disease (NAD); 2 patients with liver cirrhosis before the improvement program with CIP-LCH-2012 gave up the treatment after 1 course of therapy; 1 patient died of infectious shock after chemotherapy with severe pulmonary infection and intestinal infection. All 13 patients had grade 3 of blood and lymphatic system toxicity; 10 patients had grade 1 of hepatobiliary and gastrointestinal side effects; 3 patients with liver cirrhosis before the improvement program had grade 2 or grade 3 of hepatobiliary system and gastrointestinal system side effects, including 1 patient of death.</p><p><b>CONCLUSION</b>The improvement program of CIP-LCH-2012 had significant efficacy for children with refractory high-risk and relapsed LCH. The cladribine-associated toxicity was of significant myelosuppression, which may be tolerated in the most children patients. The program could be considered as a recommended salvage therapy for multi-system LCH (MS-LCH) after failure of first-line therapy, and as a first-line therapy for MS-LCH with risk organ injury. The program should be used with caution or dose-adjustment consideration for pre-treatment of severe organ damage exist, especially cirrhosis.</p>

Discrepant Results for BRAF V600E Mutation Among Different Specimens in a Case of Hairy Cell Leukemia

No abstract available.

Clinico-pathological presentation and therapeutic options for hairy cell leukemia

To look at clinical and hematological presentation as well as treatment outcome of patients with diagnosis of Hairy Cell Leukemia [HCL] in our population. All patients diagnosed with HCL by morphological and immunohistochemical methods presenting to Medical Oncology Ward at Hayatabad Medical Complex, Peshawar since August 2008 were included in the study. Out of 7 patients diagnosed with HCL, 6 were male and 1 was female [M:F ratio 6:1]. Median age at diagnosis was 44 years. Fever, pallor, palpitations and fatigue were the commonest presenting complaints. Spleenomegaly was noted in all patients [100%]. Pancytopenia was noted in all patients at presentation. Five patients were treated with Interferon while 2 were treated with Cladribine. At 18 months of follow-up, one out five patients treated with IFN had relapse while both the patients treated with Cladribine were in complete remission. Our study showed that HCL patients present at a younger age in our region but further studies with larger sample size are required to confirm this. All patients showed a complete response to Interferon and Cladribine with all patients alive at 18 months of follow-up.

Design and synthesis of 3'-methyl-furanonucleosides and their anti-tumor activities / 药学学报

Taking 3'-Me-Ado (3'-methyladenosine) and Cladribine as the leading compounds, seventeen 3'-C-methyl-furanonucleosides were designed and synthesized. All the structures were confirmed by 1H NMR and MS. The target compounds were tested in vitro against human pulmonary carcinoma A549, human colon carcinoma LOVO and human leukemia CEM by MTT assay. The results showed that these compounds possessed moderate cytotoxicities.

Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: a single institutional experience.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of immature and abnormal bone marrow derived langerhans cells. Treatment is usually multimodal. Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and its proven efficacy in many lymphoproliferative disorders has made 2-CDA a rational choice in treatment of LCH. AIM: To evaluate the efficacy and toxicity profile of 2-CDA in children with relapsed or refractory LCH. SETTING AND DESIGN: This is a pilot study and we present the initial data of the first seven patients treated at our institution. MATERIALS AND METHODS: Seven patients of relapsed and refractory LCH were enrolled from July 2000 to June 2004. The cohort of seven patients included six males and one female with a median age at initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years). Three patients had received one prior chemotherapy regimen while the rest were heavily pretreated. Cladribine was administered over two hours IV daily for five days and repeated every four weeks. RESULTS: After a median of six courses of cladribine (range, 2 to 9), two (33%) patients achieved PR and two (33%) patients have SD on imaging but are clinically better. None experienced grade 3 or 4 hematologic toxicity. At a median follow-up of 19 months (range, 8 to 52 months), five patients remain alive and one patient has died. CONCLUSION: Our study shows that single agent 2-CDA is active and well-tolerated in children with relapsed or refractory LCH.