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.

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.

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

No abstract available.

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

No abstract available.

Hairy-cell leukemia: a rare blood disorder in Asia.

We report a 68-year-old Indian man who was referred to the Hematology Unit for investigation for thrombocytopenia, an incidental finding during a pre-operative screening for prostatectomy. Physical examination was unremarkable. There was no splenomegaly, hepatomegaly or lymphadenopathy. Complete blood counts showed normal hemoglobin and total white cell count with moderate thrombocytopenia. Hairy-cell leukemia was diagnosed based on peripheral blood film, bone-marrow aspirate and trephine biopsy findings, supported by immunophenotyping results by flow cytometry. The purpose of this report is to create awareness of this uncommon presentation and to emphasize that a single-lineage cytopenia or absence of splenomegaly does not exclude the diagnosis of hairy-cell leukemia. Careful attention to morphological detail is important for early diagnosis, especially when low percentages of "hairy" cells are present in the peripheral blood and bone marrow. Early diagnosis is important to ensure that patients obtain maximum benefit from the newer therapeutic agents that have greatly improved the prognosis in this rare disorder.

Hairy cell leukaemia with advanced treatment - a case report.

A case of hairy cell leukaemia (HCL), a rare leukaemia, is reported here. The patient was presented with high grade continuous fever with left upper abdominal discomfort for 6 days. He was moderately anaemic, had no peripheral lymphadenopathy with mild hepatosplenomegaly. He was anaemic (Hb-7.8 gm/dl), total leukocyte count was 20 x 109/L. Peripheral blood film showed lymphocytosis (92%) with neutropenia (8%) and absolute neutophil count (ANC) was 1 x 109/L. On review, 88% of the peripheral cells had peripheral hairy projections resembling hairy cell (HC). Bone marrow examination was consistent with HCL (morrow hairy cell = 52%) including marker studies. Tartrate resistant acid phosphatase test (TRAP) was also positive. He had opportunistic mycobecterial infection giving a positive bronchial lavage for acid fast bacilli. After controlling the infection he was advised a single dose chemotherapy of 2-chlorodeoxyadenosine (2-CDA). After that he was in partial remission and after 25 months clinical and pathological relapses occurred and a second dose of 2-CDA was given and the patient went into complete remission.

Tratamento ambulatorial com 2-clorodeoxiadenosina para doenças linfoproliferativas / Treatment of lymphoproliferatives syndromes and indolent lymphomas by 2-clorodexiadenosina in outpatient reginer

O presente estudo trata da experiência clínica do uso do 2-clorodeoxiadenosina no tratamento da tricoleucemia, síndromes linfoproliferativas e linfomas indolentes. O modo de administraçäo usado em todos os casos exceto dois, foi o da infusäo endovenosa diária por 2 horas, durante cinco dias, com ciclos mensais, num esquema ambulatorial. Dos sete casos de tricoleucemia, tratados com um único ciclo, todos tiveram regressäo da esplenomegalia e 5/7 normalizaram o hemograma. Após um segmento de 2-14 meses, todos os pacientes permaneceram com a doença controlada. Foram tratados sete casos com leucemia linfóide crônica refratária à quimioterapia oral bem como a um esquema de poliquimioterapia endovenosa. Em quatro casos houve uma remissäo parcial, mantida por 3-13 meses.Três pacientes que foram resistentes ao tratamento morreram por infecçäo. Os dois casos de leucemia pró-linfocítica receberam dois e três ciclos respectivamente, com controle da doença por 15 e seis meses respectivamente. Todos estes achados bem como uma observaçäo preliminar com resposta em dois pacientes com linfomas indolentes confirmam os dados da literatura de que o 2-CdA é um quimioterápico com boa açäo em síndromes linfoproliferativas em linfomas indolentes. Sua administraçäo é segura no regime de administraçäo usado, o que torna seu uso mais barato e prático.

Experiencia de tratamiento de la leucemia de células vellosas con clorodeoxiadenosina y con interferón alfa 2 / Treatment's experience of hairy cell leukemia with chlorodeoxyadenosine and alpha 2 interferon

Cinco pacientes con Leucemia de Células Vellosas fueron tratados con clorodeoxiadenosina (4291-63-8), análogo de las purinas, resistente a la adenosin deaminasa, a dosis 0,1 mg/kg/día, siete días, endovenoso continuo. Todos presentaban infiltración de médula ósea, esplenomegalia y pancitopenia. Media de neutrófilos 0.5 x 10 9/L; de plaquetas 53.8 x 10 9/L, y de hemoglobina 7,52 g/dL. Todos lograron remisión completa, seguimiento de 9 a 33 meses; dos fallecieron a los nueve y dieciséis meses debido a otras causas. La recuperación plaquetaria precedió a la de neutrófilos y hemoglobina. El tiempo medio de recuperación de neutrófilos fue 41 días. Todos recibieron G-CSF a 5 microg./kg. Toxicidad: mielosupresión y fiebre. Promedio de transfusiones de GRD: 7 unidades y de plaquetas 5 procedimientos. Dos pacientes fueron tratados con interferón alfa 2 a 4.5 MU/día por medio, subcutáneo, por un año. Ambos obtuvieron remisión hematológica completa a los doce y trece meses de tratamiento. El nivel de hematocrito y hemoglobina se normalizó a los tres y cuatro meses de tratamiento; el recuento leucocitario a los cuatro y siete meses, y las plaquetas a los dos meses. Sólo un paciente requirió transfusión de GRD: cuatro unidades. Toxicidad: prurito generalizado, síndrome pseudogripal, náuseas y cefalea. Ambos persisten en remisión hematológica completa luego de veintisiete y cinco meses de finalizado el tratamiento. El interferón alfa y la clorodeoxiadenosina ofrece ventajas por la alta probabilidad de remisiones completas a corto plazo y durables en la evolución.

Leucemia megacarioblástica da criança: apresentçäo de um caso e revisäo da literatura / Megakaryocytic leukemia in child: report of a case and literature review

Os autores fazem a apresentaçäo de um caso de leucemia aguda näo-linfóide em uma criança do sexo feminino, branca, com 27 meses de idade, que foi encaminhada ao St. Jude Children's Research Hospital, com suspeita clínica e radiográfica de neuroblastoma. Esse último diagnóstico foi considerado devido a paciente ser de baixa idade, apresentar dor óssea, anemia, e lesöes osteolíticas disseminadas. Após extensa avaliaçäo, o diagnóstico de leucemia aguda megacarioblástica (LMCA) foi firmado. A definiçäo desse tipo de leucemia, neste caso, se baseou nos achados citomorfológicos do infiltrado celular da medula óssea, e propriedades citoquímicas e imunofenotípicas das células leucêmicas. As características clínicas, biológicas e de resposta ao tratamento da LMCA säo descritas, enfatizando principalmente aquelas que ocorrem em crianças de baixa idade.