A Novel JAK2 Fusion in T-Cell Prolymphocytic Leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive mature T-cell malignancy characterized by marked lymphocytosis, B symptoms, lymphadenopathy, and hepatosplenomegaly. There is no standard treatment approach, and in the absence of an allogeneic transplant, the prognosis remains poor. The disease-defining cytogenetic abnormality in T-PLL is the juxtaposition of the TCL1-family oncogene to the TCR gene enhancer locus primarily due to an inversion of chromosome 14, that is, inv(14). The application of next-generation sequencing technologies led to the discovery of highly recurrent gain-of-function mutations in JAK1/3 and STAT5B in over 70% of T-PLL providing opportunities for therapeutic intervention using small molecule inhibitors. Additional genetic mechanisms that may contribute to the pathogenesis of T-PLL remain unknown. Herein we describe the identification of a novel gene fusion SMCHD1::JAK2 resulting from a translocation between chromosome 9 and 18 involving SMCHD1 exon 45 and JAK2 exon 14 (t(9;18)(p24.1;p11.32)(chr9:g.5080171::chr18:g.2793269)), a previously undescribed genetic event in a patient with T-PLL harboring the key disease defining inv(14) resulting in rearrangement of TCL1 and TRA/D. In this manuscript, we describe the clinical and genetic features of the patient's disease course over a 25-month post-treatment duration using ruxolitinib and duvelisib.

[TCL1-family negative T-cell prolymphocytic leukemia with rapid progression of extranodal disease despite a normal white blood cell count].

Here we describe the case of a 69-year-old man who was found to have moderate thrombocytopenia and severe splenomegaly during a medical checkup at the age of 67. At the first visit, his white blood cell (WBC) count was 7,400/µl with 80% lymphocytes, and bone marrow aspiration showed 24% atypical lymphocytes. Flow cytometry of atypical lymphocytes was positive for mature T-cell markers, and T-cell clonality was revealed by T-cell receptor gene rearrangement. TCL1 was negative on immunohistochemistry. We diagnosed TCL1-family negative T-cell prolymphocytic leukemia (T-PLL) and employed watchful waiting. Thirty months after diagnosis, the patient developed urinary retention and right lower-limb paresis despite a normal WBC count, and an extradural tumor around the thoracic vertebrae and spinal cord compression were detected. The tumor was diagnosed as extranodal involvement of TCL1-family negative T-PLL, but the patient's general condition deteriorated rapidly, and no treatment was possible. T-PLL is a rare disease characterized by leukocytosis, and the WBC count generally increases with disease progression. Although blood counts are recommended for observation, it is important to keep in mind that the disease may worsen even if blood counts do not change.

Leveraging machine learning for predicting acute graft-versus-host disease grades in allogeneic hematopoietic cell transplantation for T-cell prolymphocytic leukaemia.

Orphan diseases, exemplified by T-cell prolymphocytic leukemia, present inherent challenges due to limited data availability and complexities in effective care. This study delves into harnessing the potential of machine learning to enhance care strategies for orphan diseases, specifically focusing on allogeneic hematopoietic cell transplantation (allo-HCT) in T-cell prolymphocytic leukemia. The investigation evaluates how varying numbers of variables impact model performance, considering the rarity of the disease. Utilizing data from the Center for International Blood and Marrow Transplant Research, the study scrutinizes outcomes following allo-HCT for T-cell prolymphocytic leukemia. Diverse machine learning models were developed to forecast acute graft-versus-host disease (aGvHD) occurrence and its distinct grades post-allo-HCT. Assessment of model performance relied on balanced accuracy, F1 score, and ROC AUC metrics. The findings highlight the Linear Discriminant Analysis (LDA) classifier achieving the highest testing balanced accuracy of 0.58 in predicting aGvHD. However, challenges arose in its performance during multi-class classification tasks. While affirming the potential of machine learning in enhancing care for orphan diseases, the study underscores the impact of limited data and disease rarity on model performance.

[Durable remission of T-cell prolymphocytic leukemia with CLEC16A::IL2 after allogeneic hematopoietic stem cell transplantation].

A 64-year-old woman presented with fine motor impairment in both hands. MRI revealed a contrast-enhanced lesion in the medulla oblongata. Lymphoid cells with abnormal blebs were observed and a CD4+/CD8+ double positive (DP) T cell population was detected by flow cytometry (FCM) in the bone marrow (BM) and the peripheral blood (PB). CLEC16A::IL2 fusion gene was identified by whole exome sequencing with DNA prepared from DP T cells. Clonal rearrangement of the T-cell receptor gene and expression of TCL1A protein were detected. This led to a diagnosis of T-cell prolymphocytic leukemia (T-PLL) with central nervous system (CNS) infiltration. Abnormal cells in BM and PB became undetectable on microscopy and FCM, and the CNS lesion disappeared on MRI after second-line therapy with alemtuzumab. Meanwhile, the CLEC16A::IL2 fusion mRNA remained detectable in PB. Allogeneic hematopoietic stem-cell transplantation was performed, and the fusion mRNA has now been undetectable for more than 5 years since transplantation. This is the first report of a T-PLL case with a CLEC16A::IL2 fusion gene.

T-cell prolymphocytic leukemia: Epidemiology and survival trends in the era of novel treatments.

Survival remains poor for T-cell prolymphocytic leukemia, though treatment in recent years, associated with access to novel therapies, and management at academic medical centers is associated with improved outcomes. There remains a critical need to improve the available treatment options for this population, and access to specialized academic medical centers, comprehensive supportive care, clinical trials, and early palliative care remains essential for T-PLL patients.

Clinical Characteristics of Aggressive NK-Cell Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore and summarize the clinical characteristics and treatment of aggressive NK-cell leukemia (ANKL), and provide new insights for clinical diagnosis and treatment of this disease.@*METHODS@#The clinical data of 7 patients with ANKL admitted to the First Affiliated Hospital of Wannan Medical College from March 2014 to July 2021 were retrospectively analyzed, and their clinical characteristics, laboratory and imaging results, treatment and outcomes were analyzed.@*RESULTS@#Among the 7 patients, 5 were males and 2 were females, with a median age of 47 (33-69) years old. The morphology of bone marrow cells in 7 patients showed similar large granular lymphocytes. Immunophenotyping revealed abnormal NK cells in 5 cases. By the end of follow-up, 6 cases died and 1 case survived, with a median survival time of 76.9 (4-347) days.@*CONCLUSION@#ANKL is a rare disease with short course and poor prognosis. If combined with hemophagocytic syndrome (HPS), the prognosis is even worse. There is no unified treatment method at present, and the use of PD-1 inhibitors may prolong the survival in some patients.

Research Advances of Genetics, Diagnosis and Treatment of T-cell Prolymphocytic Leukemia--Review / 中国实验血液学杂志

T-cell prolymphocytic leukemia (T-PLL) is a rare but highly aggressive and malignant mature T-lymphoid tumor. The diagnosis of T-PLL mainly depend on genetic characteristics, clinical manifestations, cell morphology and immunophenotype. At present, clinical treatment is mainly aimed at improving the response rate and prolonging the remission period. With the development of new molecular biology technologies, researchers have gained a deeper understanding of the pathogenesis and related genetics of T-PLL, targeted drugs, including HDAC inhibitors, JAK/STAT inhibitors, AKT inhibitors and BCL-2 inhibitors, are also under evolution and providing the new opportunities to improve the efficacy of therapy. In this review, the advances in genetics and treatment of T-PLL were summarized briefly.

Small cell variant of T-cell prolymphocytic leukemia with atypical presentation

No abstract available.

Leucémie lymphoïde chronique au Niger: une étude de 99 cas au service d'onco-hématologie de l'hôpital national de Niamey

Introduction. Le but de l'étude est de décrire les caractéristiques épidémiologiques et cliniques de la leucémie lymphoïde chronique (LLC) au Niger. C'est la première étude nigérienne spécifiquement consacrée à cette maladie. Méthodologie. Nous avons mené une étude rétrospective couvrant la période de janvier 2000 à décembre 2011 (12 ans) dans le service d'Onco-Hématologie de l'HNN. Le diagnostic de LLC était retenu sur la base d'une hyper lymphocytose sanguine > 15 000/mmᶾ associée à une infiltration médullaire de plus de 40% de lymphocytes mâtures. Les données ont été recueillies dans les dossiers de malades. Nos variables d'étude étaient les aspects épidémiologiques, cliniques et évolutifs de la maladie. Résultats. Au cours de la période d'étude, 99 patients ont été colligés soit une fréquence d'environ huit cas par an. Le sex ratio était de 0,47 et la moyenne d'âge des patients de 53,25 ans (extrêmes: 30 à 82 ans). L'échantillon était constitué de 89 % de paysans (cultivateurs, éleveurs femmes au foyer). La durée moyenne des troubles avant la première consultation était de 24 mois. Les principaux motifs de consultation étaient: la splénomégalie (81,8%), les adénopathies (38,4%) et l'anémie (21,2%). Les principaux signes physiques étaient: les adénopathies (84,8%); la splénomégalie (80,8%); la pâleur cutanéo-muqueuse (31,3%); la fièvre (29,3%) et l'hépatomégalie (25,3%). Selon la classification anatomo-clinique de Binet, 39 patients (39,4%) étaient au stade A, 16 cas (16,2%) au stade B et 44(44,4%) au stade C. Conclusion. À Niamey, la LLC est une maladie de l'adulte jeune diagnostiquée souvent à un stade avancé du fait du retard de la première consultation

Bronquiolitis obliterante tras trasplante de progenitores hematopoyéticos / No disponible

El trasplante alogénico de progenitores hematopoyéticos es un tratamiento establecido con un alto potencial curativo para varias enfermedades hematológicas. La enfermedad del injerto contra huésped (EICH) crónica es una complicación mayor de este procedimiento y es la principal causa de mortalidad tardía tras el trasplante. La bronquiolitis obliterante es una complicación particularmente grave que ocurre en el 10-15% de los pacientes con enfermedad injerto contra huésped extensa y con frecuencia es refractaria a tratamiento. Si no hay respuesta al tratamiento inmunodepresor convencional tras 3-6 meses de tratamiento, el pronóstico de estos pacientes es infausto. Presentamos el caso de una mujer de 57 años diagnosticada de un síndrome linfoproliferativo crónico T, que desarrolló bronquiolitis obliterante un año después de un trasplante alogénico de progenitores hematopoyéticos

Hematopoietic stem cell transplantation is an established treatment with a high curative potential for various hematological diseases. Chronic graft-versus-host disease is a major complication of this procedure and is the leading cause of late mortality after transplantation. Bronchiolitis obliterans is a particularly serious complication that occurs in 10-15% of patients with extensive graft-versus-host disease and is often refractory to treatment. If there is no response to conventional immunosuppressive treatment after 3-6 months of treatment, the prognosis of these patients is unfortunate. We report the case of a 57 year old woman diagnosed with a chronic T lymphoproliferative syndrome who developed bronchiolitis obliterans one year after an hematopoietic stem cell transplantation

Leucemia prolinfocítica T variante de células cerebriformes: presentación de un caso y revisión de la literatura / Cerebriform variant type of T cell prolymphocytic leukemia: report of one case

T cell Prolymphocytic Leukemia (T-PLL) is a rare and aggressive mature T cell Lymphocyte Leukemia. Twenty five percent of cases present as a small cell variant, and only 5% as a cerebriform variant. We report a 58 year-old man with rapidly progressive severe leukocytosis, skin lesions, lymphadenopathy, hepatosplenomegaly and pleural effusion. The lymphocytes had a cerebriform type. The diagnosis of T-PLL variant was made by morphology and immunophenotype study of peripheral blood. Karyotype was found to be complex. He was refractory to chemotherapy and died two months later.

Clinical and laboratory features of T-cell prolymphocytic leukemia in China / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory characteristics and survival of Chinese patients with T- cell prolymphocytic leukemia (T-PLL).</p><p><b>METHODS</b>Eleven patients with T-PLL admitted in our hospital from Jan 2006 to Oct 2012 were retrospectively analyzed.</p><p><b>RESULTS</b>Of the 11 patients, nine were males and two females, with the median age of 56.0(19-69) years old. All the patients, except for three, presented with leukocytosis. The incidence of hyperleukocytosis (1/11) was less frequent than that in the British series (75%) (P=0.000). Lymphocyte counts in peripheral blood were increased in 9 of the 11 patients with the median absolute lymphocyte count (ALC) of 17.22(0.58-148.83)×10⁹/L. Superficial lymphadenopathy and splenomegaly were the most common physical signs. It was common that serum lactate dehydrogenase (LDH) and beta 2 microglobulin(β2-MG)were higher than normal level. All cases were positive for CD2/CD3/CD5/TCRαβ, negative for CD1a /HLA-DR and TdT, and most of them were strong positive for CD7 expression. By chromosome analyses, most cases. (9/10) have normal chromosome. This rate is significantly higher than that of the British and American series (3% and 25%, respectively) (P=0.000, P=0.001). The 14q11 abnormality and trisomy 8q, which are common among Western cases, were not observed in any of our cases. With a median follow-up of 23.0 months, three patients died. Two year progress free survival (PFS) and overall survival (OS) were 53.3% and 50%, respectively. There were 3 patients with PFS over a number of years, whether it should be considered as the T-chronic lymphocytic leukemia (T-CLL) is worthy of further studies.</p><p><b>CONCLUSION</b>The common clinical manifestations of T-PLL patients were increased lymphocyte counts and lymphadenopathy as well as splenomegaly. And most cases have high level of blood LDH and β2- MG and normal chromosome karyotype.</p>

Selective embolization of the internal iliac arteries for the treatment of intractable hemorrhage in children with malignancies / 소아과

PURPOSE: Acute internal hemorrhage is an occasionally life-threatening complication in pediatric cancer patients. Many therapeutic approaches have been used to control bleeding with various degrees of success. In this study, we evaluated the efficacy of selective internal iliac artery embolization for controlling acute intractable bleeding in children with malignancies. METHODS: We retrospectively evaluated the cases of 6 children with various malignancies (acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, T-cell prolymphocytic leukemia, Langerhans cell histiocytosis, and rhabdomyosarcoma), who had undergone selective arterial embolization (SAE) of the internal iliac artery at the Chonnam National University Hwasun Hospital between January 2004 and December 2009. SAE was performed by an interventional radiologist using Gelfoam(R) and/or Tornado(R) coils. RESULTS: The patients were 5 boys and 1 girl with median age of 6.9 years (range, 0.7-14.8 years) at the time of SAE. SAE was performed once in 4 patients and twice in 2, and the procedure was unilateral in 2 and bilateral in 4. The causes of hemorrhage were as follows: hemorrhagic cystitis (HC) in 3 patients, procedure-related internal iliac artery injuries in 2 patients, and tumor rupture in 1 patient. Initial attempt at conservative management was unsuccessful. Of the 6 patients, 5 (83.3%) showed improvement after SAE without complications. CONCLUSION: SAE may be a safe and effective procedure for controlling acute intractable hemorrhage in pediatric malignancy patients. This procedure may obviate the need for surgery, which carries an attendant risk of morbidity and mortality in cancer patients with critical conditions.

Cytologic Features of Ascitic Fluid Complicated by Small Cell Variant T-cell Prolymphocytic Leukemia: A Case Report / 대한세포병리학회지

T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell lymphoproliferative disorder with a post-thymic mature T-cell phenotype. The disease is characterized by rapidly rising lymphocytosis, lymphadenopathy, and splenomegaly. The clinical course is usually aggressive and progresses with frequent skin lesions and serous effusions. In 25% of cases, leukemic cells are small and tumor cells may not have a discrete nucleolus under light microscopy. Although the presence of characteristic cytoplasmic protrusions or blebs in tumor cells is a common morphologic finding in the peripheral blood film irrespective of the nuclear features, small cell variants lacking the typical nuclear features can cause diagnostic problems in clinical cytology. Furthermore, the small leukemic cells can share some cytologic findings with lymphocyte-rich serous effusions caused by non-neoplastic reactive lymphocytosis as well as other small lymphocytic lymphoproliferative disorders. Here, we describe the cytological findings of ascitic fluid complicated by small cell variant T-PLL in a 54-year-old man, the cytology of which was initially interpreted as small lymphocytic malignancy such as small lymphocytic lymphoma/chronic lymphocytic leukemia.

A Case of Unspecified Mature T-cell Leukemia with Clover-shaped, Multi-lobated Nuclei

Mature T-cell leukemias are a group of neoplasms derived from mature or post-thymic T-cells, and a number of distinctive disease entities have been defined in the World Health Organization (WHO) classification. Here we report a 54-year-old female patient with multi-lobated atypical cells expressing the classic T-cell antigens involving multiple lymph nodes, peripheral blood, and bone marrow. The clinical, laboratory, and pathologic features of her disease did not fit into any of the entities in the WHO Classification. There was no evidence of rapidly rising lymphocyte counts, TCL1 expression, eosinophilia, erythroderma, Sezary cells, autoimmune phenomena, cytotoxic granules, nor evidence of HTLV-1 infection, and thus, T-cell prolymphocytic leukemia, Sezary syndrome, T-cell granular lymphocytic leukemia, and adult T-cell leukemia/lymphoma were all ruled out. This case suggests that further characterization and definition of the "unclassifiable" cases of mature T-cell neoplasm is needed to better understand the group of disorders.