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Prolymphocytic Leukemia

T-PLL

Prolymphocytic leukemia, encompassing both T-cell and B-cell subtypes, is one of the most aggressive forms of leukemia characterized by a rapidly deteriorating clinical course and poor survival rates. Hepatosplenomegaly, marked leukocytosis, and cutaneous lesions such as nodules and a maculopapular rash are some of the main symptoms. Laboratory assessment, examination of a peripheral blood smear, and a histopathological examination with immunohistochemistry are key components of the diagnostic workup.


Presentation

Described as a type of leukemia having a rather poor prognosis, prolymphocytic leukemia (PLL) is a rare lymphoid malignancy of mature T or B cells [1] [2] [3] [4]. Prolymphocytic leukemia is primarily encountered in elderly patients, with a slight predisposition toward male gender [1] [2] [4]. In addition to the aggressive nature of this malignant disease, a very limited response to chemotherapy, and frequent relapses, a delayed diagnosis is an equally important reason for such low survival rates - 5-year survival established around 20%, while median survival is 4-7.5 months and 3 years for T-cell PLL and B-cell PLL, respectively [1] [2] [4] [5]. Although several reports have documented a rather slow clinical course of prolymphocytic leukemia, or even asymptomatic patients [1] [5], symptoms develop rapidly in the majority of cases, with splenomegaly (sometimes accompanied by hepatomegaly) and lymphadenopathy being the most prominent [1] [2] [3]. In a small, but a significant number of cases, skin lesions in the form of nodules, a maculopapular rash (either generalized or local), or erythrodermia in rare cases, are observed, and primarily appear in T-cell PLL [1] [2] [4]. Periorbital or conjunctival edema is another important feature of prolymphocytic leukemia and is more commonly seen in T-cell PLL [1]. Pleuroperitoneal serous effusions are rare complications seen in T-cell PLL, but are absent in B-cell PLL, which might be used as a distinguishing clinical feature [1] [2] [4].

Splenomegaly
  • However, the generalized lymphadenopathy and splenomegaly did not improve. The patient underwent splenectomy to palliate abdominal distension and hypersplenism.[ncbi.nlm.nih.gov]
  • A 69-year-old woman was admitted to our hospital because of massive splenomegaly and leukocytosis. Peripheral blood showed hemoglobin (Hb) 7.4 g/dl, platelets 48 x 10(9)/l and white blood cells (WBC) 50.3 x 10(9)/l with 90% prolymphocytes.[ncbi.nlm.nih.gov]
  • This patient presented with an asymptomatic leukocytosis and splenomegaly.[ncbi.nlm.nih.gov]
  • T-cell prolymphocytic leukemia (T-PLL) is an uncommon chronic lymphoproliferative disorder characterized by lymphadenopathy, splenomegaly, and lymphocytosis.[ncbi.nlm.nih.gov]
  • Furthermore, palpation of the abdomen, as a component of the physical examination, will confirm the presence of splenomegaly and indicate additional testing.[symptoma.com]
Massive Splenomegaly
  • A 69-year-old woman was admitted to our hospital because of massive splenomegaly and leukocytosis. Peripheral blood showed hemoglobin (Hb) 7.4 g/dl, platelets 48 x 10(9)/l and white blood cells (WBC) 50.3 x 10(9)/l with 90% prolymphocytes.[ncbi.nlm.nih.gov]
  • This is a rare chronic lymphoproliferative disorder seen in elderly in which patients have high total leukocyte count along with massive splenomegaly.[medical-labs.net]
  • Patients presenting with massive splenomegaly may be effectively palliated with splenic irradiation or splenectomy. Rituximab is a promising agent and further investigations are warranted to better define its role in treatment of this disorder.[ncbi.nlm.nih.gov]
  • PLL is characterized by leukocytosis, massive splenomegaly with little or no lymphadenopathy, anemia, thrombocytopenia, and male prevalence. T-cell PLL is especially rare and aggressive. It is known that T-PLL may be accompanied by leukemia cutis.[ekjm.org]
  • ; splenectomy for symptomatic improvement T cell phenotype: Alemtuzumab (anti-CD52 monoclonal antibody) may achieve favorable response Autologous and allogeneic stem cell transplant as adjunctive treatment for patients in remission Gross description Massive[pathologyoutlines.com]
Lymphocyte Disorder
  • Prolymphocytic leukemia (PLL) is a rare lymphocytic disorder characterized by marked lymphocytosis and splenomegaly and represents only 2% of all mature lymphocytic leukemias in adults over the age of 30.[ncbi.nlm.nih.gov]
  • PubMed Google Scholar Bartlett NL, Longo DL: T-small lymphocyte disorders. Semin Hematol 1999, 36: 164–170.[ehoonline.biomedcentral.com]
Anemia
  • Biological assays also showed a hemolytic anemia and a clotting factor V decrease. The patient was first treated by methylprednisone for 3 weeks. During this period the lymphocyte count decreased.[ncbi.nlm.nih.gov]
  • A complete blood cell count revealed leukocytosis, anemia and thrombocytopenia with 80% lymphocytes.[ncbi.nlm.nih.gov]
  • There was marked leucocytosis, anemia and thrombocytopenia (WBC 445 x 103 sub/ml, Hb 8.5 gm/dl, Platelet 25 x 103 sub/microl) with 60% prolymphocytes in the peripheral blood. Bone marrow was hypercellular with an excess of prolymphocytes.[ncbi.nlm.nih.gov]
  • The patient was treated with prednisolone followed by 4 weekly doses of rituximab, which led to resolution of the anemia and complete response of the underlying leukemia.[ncbi.nlm.nih.gov]
  • Anemia and thrombocytopenia were not observed.[ncbi.nlm.nih.gov]
Weight Loss
  • A 68 year old male presented with a history of weakness and weight loss of two months duration. Clinical examination revealed pallor, enlarged cervical and axillary lymph nodes and splenomegaly. He also had a maculo- papular skin rash.[ncbi.nlm.nih.gov]
  • A 77-year-old woman presented to the outpatient hematology clinic in August 2001 with leukocytosis, recurrent bacterial infections, sweating and weight loss.[ncbi.nlm.nih.gov]
  • Bruising easily Slow wound healing Decreased appetite and feeling full quickly Unexplained weight loss Unexplained fatigue Persistent, unexplained abdominal pain on the left side from an enlarged spleen Frequent infections Fever Chills Night sweats If[cancer.net]
  • Hepatosplenomegaly Elevated white blood cell count 100,000/microL Splenomegaly Generalized lymphadenopathy Occasional skin involvement Clinical Features B symptoms Fever Swelling in the lymph nodes Night sweats Persistent fatigue Fever Persistent fatigue Weight-loss[wikidoc.org]
Fever
  • The patient initially suffered from anorexia, skin pigmentation, fever and hepatosplenomegaly. Bone marrow smear described leishmania and antibody test was positive. VL was diagnosed and he was given antimony gluconate therapy.[ncbi.nlm.nih.gov]
  • Swelling in the lymph nodes Night sweats Persistent fatigue Fever Persistent fatigue Weight-loss Diagnosis Peripheral blood smear Prolymphocytes (90%) Biomarkers CD20 Peripheral blood smear Medium-sized lymphoid cells Moderately condensed chromatin and[wikidoc.org]
  • Bruising easily Slow wound healing Decreased appetite and feeling full quickly Unexplained weight loss Unexplained fatigue Persistent, unexplained abdominal pain on the left side from an enlarged spleen Frequent infections Fever Chills Night sweats If[cancer.net]
  • Symptoms A person with PLL usually has: a larger than normal spleen or liver a very high white blood cell count low red blood cell count (called anemia) low platelet count (called thrombocytopenia) B symptoms (unexplained fever, drenching night sweats[cancer.ca]
Fatigue
  • He also complained of having fatigue, general weakness, and disequilibrium. His visual acuity was 20/20 bilaterally. His intraocular pressures were 34 mm Hg oculus dexter (OD) and 35 mm Hg oculus sinister (OS).[ncbi.nlm.nih.gov]
  • Fever Persistent fatigue Weight-loss Diagnosis Peripheral blood smear Prolymphocytes (90%) Biomarkers CD20 Peripheral blood smear Medium-sized lymphoid cells Moderately condensed chromatin and a visible nucleolus Biomarkers CD52 References[wikidoc.org]
  • We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 13, 2019[patientslikeme.com]
  • We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 30, 2019[patientslikeme.com]
  • Bruising easily Slow wound healing Decreased appetite and feeling full quickly Unexplained weight loss Unexplained fatigue Persistent, unexplained abdominal pain on the left side from an enlarged spleen Frequent infections Fever Chills Night sweats If[cancer.net]
Soft Tissue Mass
  • Radiologic and physical examination demonstrated an ovoid soft tissue mass of the lateral external auditory canal that, after biopsy and flow cytometry studies, was found to be T-cell prolymphocytic leukemia.[ncbi.nlm.nih.gov]
Left Upper Quadrant Pain
  • To present a case report of an 83-year-old female with underlying dementia and a 1-2 month history of left upper quadrant pain.[ncbi.nlm.nih.gov]
Hepatosplenomegaly
  • T-cell prolymphocytic leukaemia (T-PLL) is a rare aggressive lymphoid disease featured by a significant increased lymphocyte count and obvious hepatosplenomegaly with poor prognosis.[ncbi.nlm.nih.gov]
  • This patient's condition was diagnosed as T-cell prolymphocytic leukemia based on the findings of lymphocytosis, abnormal immunophenotype, hepatosplenomegaly, lymphadenopathy, and cutaneous involvement.[ncbi.nlm.nih.gov]
  • Aggressive symptoms, such as lymphocytosis, lymphadenopathy, pleural effusion, cutaneous involvement and hepatosplenomegaly, developed during the progressive phases. Levels of serum soluble interleukin 2 receptor increased when symptoms worsened.[ncbi.nlm.nih.gov]
  • Hepatosplenomegaly was absent. He was diagnosed as having T-PLL and was treated with combination chemotherapy. Six months later the leukemic cell became chemoresistant.[ncbi.nlm.nih.gov]
  • Eight years after the initial diagnosis, she developed lymphadenopathy and hepatosplenomegaly. A complete blood cell count revealed leukocytosis, anemia and thrombocytopenia with 80% lymphocytes.[ncbi.nlm.nih.gov]
Hepatomegaly
  • Both disorders have an aggressive clinical course, lymphocytosis with characteristic morphology, lymphadenopathy, hepatomegaly, characteristic cytogenetic abnormalities and mature T cell phenotypes. Skin lesions, however, are mainly found in T-PLL.[ncbi.nlm.nih.gov]
  • Although several reports have documented a rather slow clinical course of prolymphocytic leukemia, or even asymptomatic patients, symptoms develop rapidly in the majority of cases, with splenomegaly (sometimes accompanied by hepatomegaly) and lymphadenopathy[symptoma.com]
  • Half of the patients have hepatomegaly and lymphadenopathy. Skin manifestations (maculopapular rash, erythroderma) occur in less than 20% of cases.[path.upmc.edu]
  • Common presenting signs include splenomegaly (73%), lymphadenopathy (53%), hepatomegaly (40%), skin manifestations (27%), pleural effusions (12%), and high leukocyte count ( 100 10 9 cells per liter in 75%).[stm.sciencemag.org]
Palpable Purpura
  • Following the first dose of therapy with bendamustine, the patient developed severe generalized maculopapular rash, which subsequently progressed to exuberant, non-blanching palpable purpura with hemorrhagic plaques suspicious for leukocytoclastic vasculitis[ncbi.nlm.nih.gov]
Aural Fullness
  • An adult man in good health came to receive medical attention because of a sensation of aural fullness.[ncbi.nlm.nih.gov]
Blurred Vision
  • A 46-year-old woman presented with pain and blurred vision in the right eye. She was found to have signs of panuveitis with a central exudative retinal detachment.[ncbi.nlm.nih.gov]
Dysphasia
  • An 89-year-old woman who had been treated for Hashimoto's thyroiditis for 20 years presented with a progressively enlarging thyroid mass accompanied by dyspnea and dysphasia.[ncbi.nlm.nih.gov]

Workup

A thorough diagnostic workup is mandatory in order to identify prolymphocytic leukemia in its early stages. Firstly, a detailed patient history must be obtained, during which the course, as well as the progression of symptoms, must be noted. Furthermore, palpation of the abdomen, as a component of the physical examination, will confirm the presence of splenomegaly and indicate additional testing. A complete blood count (CBC) is the cornerstone of the laboratory workup, showing profound lymphocytosis (over 100 × 109/L), whereas anemia/thrombocytopenia is observed in approximately 50% of cases [1] [2] [5]. Circulating levels of lactate dehydrogenase (LDH) are also elevated [1]. Once there is valid clinical suspicion of a lymphoproliferative process, examination of the peripheral blood smear needs to be carried out, where the presence of medium-sized prolymphocytes with intense nongranular basophilic cytoplasm containing protrusions or blebs and large (often irregular-shaped) nuclei with single prominent nucleoli is highly suggestive of a T-cell prolymphocytic leukemia [1] [4] [6]. A somewhat larger size of prolymphocytes, however, is characteristic for B-cell PLL [1]. Recognizing B-cell PLL may be challenging, because of its rather rare occurrence and similar findings compared to other mature B-cell disorders (eg. mantle cell lymphoma) [1]. To solidify the diagnosis, immunohistochemistry and phenotyping using flow cytometry is recommended - CD2, CD3, CD5 and CD7 positivity is expressed by T-cell PLL, whereas CD19, CD20, and CD22 positivity, as well as strong expression of surface membrane immunoglobulin, or SMIg, is typical for B-cell PLL [1]. For T-cell PLL, expression of T-cell receptor-1 (TCL-1) protein was examined and proposed as a prognostic factor in determining overall survival [1] [7]. Lymph node or spleen biopsies are indicated only if inconclusive findings are obtained on peripheral blood smears or when the exact type of lymphoid malignancy is not determined [1] [4]. A bone marrow biopsy will show diffuse infiltration of prolymphocytes and active hematopoiesis [4].

Cavitary Lesion
  • He was admitted to our hospital for chemotherapy and evaluation of a pulmonary cavitary lesion by wedge resection. During sedation, the patient experienced acute respiratory failure and hypovolemic shock, from which he could not be resuscitated.[ncbi.nlm.nih.gov]
Gastric Lesion
  • Endoscopic examination of the upper gastrointestinal tract revealed hemorrhage from a gastric lesion with histological involvement.[ncbi.nlm.nih.gov]

Treatment

  • Currently, there is no optimal treatment for T-cell PLL, but alemtuzumab has shown success with extending survival 1-3 years.[ncbi.nlm.nih.gov]
  • Only 3 of 9 patients (33%) responded to treatment. Furthermore, 2 of 9 patients (22%) died while on treatment. Recruitment was terminated because of these poor results.[ncbi.nlm.nih.gov]
  • Currently, the best treatment for T-PLL is IV alemtuzumab, which has resulted in very high response rates of more than 90% when given as frontline treatment and a significant improvement in survival.[ncbi.nlm.nih.gov]
  • She remains in complete remission 8 months following the discontinuation of treatment. This is the second reported case of successful treatment of B-cell PLL with rituximab.[ncbi.nlm.nih.gov]
  • The reasons why treatment may have failed are discussed (nature of disease, disease progression, treatment schedule).[ncbi.nlm.nih.gov]

Prognosis

  • T-PLL is usually refractory to chemotherapy and is a T-cell malignancy with poor prognosis.[ncbi.nlm.nih.gov]
  • PLL has poorer prognosis than chronic lymphocytic leukemia (CLL), and the patients with static disease for a longer period of time are rare. In general, B-PLL patients have better prognosis than T-PLL patients.[ncbi.nlm.nih.gov]
  • Although the therapeutic strategy for B-PLL should be determined based on the severity of the disease, RIC with allo-HSCT may be a therapeutic option for indolent B-PLL when the long-term prognosis of patients is markedly poor.[ncbi.nlm.nih.gov]
  • Claire Dearden will discuss poor prognosis variants including prolymphocytic leukemia and how we can improve outcome for these patients. Dr.[ashondemand.org]
  • Conjunctival involvement with leukemia was consistent with good visual acuity; however, it portended a poor prognosis.[ncbi.nlm.nih.gov]

Etiology

  • Gov't MeSH terms Alemtuzumab Antibodies, Monoclonal, Humanized/administration & dosage Antibodies, Monoclonal, Humanized/therapeutic use* Antineoplastic Agents/administration & dosage Antineoplastic Agents/therapeutic use* Female Graft vs Host Disease/etiology[ncbi.nlm.nih.gov]
  • Etiology (Causes) There’s no obvious cause for prolymphocytic leukemia, but it should be noted that the condition can’t be contracted from someone else, like an infection, and that it’s not hereditary (passed on from a parent).[xpertdox.com]

Epidemiology

  • Budapest, Hungary. 4 Microbiological Research Group, National Center for Epidemiology, Budapest, Hungary; University of Szeged, Faculty of Dentistry, Department of Oral Biology and Experimental Dental Research, Szeged, Hungary.[ncbi.nlm.nih.gov]
  • Prolymphocytic leukemia of T-cell type (effective October 01, 2015) Signs and Symptoms Anemia Hepatosplenomegaly Thrombocytopenia Diagnostic Exams Flow cytometry Immunohistochemistry Immunophenotyping Peripheral blood smear Progression and Transformation None Epidemiology[seer.cancer.gov]
  • Characteristics B-PLL T-PLL Epidemiology Rare Very rare Age 60-70 years 60-70 years Onset Elevated white blood cell count 100,000/microL Hepatosplenomegaly Elevated white blood cell count 100,000/microL Splenomegaly Generalized lymphadenopathy Occasional[wikidoc.org]
  • Epidemiology (incidence and distribution) B-cell prolymphocytic leukemia mainly affects patients between 65 and 70 years of age, with men and women being equally affected.[xpertdox.com]
  • Case Name (click on case name to open) Comments Size Epidemiology B-PLL is an extremely rare disease, comprising approximately 1% of lymphocytic leukemias.[wiki.clinicalflow.com]
Sex distribution
Age distribution

Pathophysiology

  • […] molecular / cytogenetics description below) Sites Peripheral blood, bone marrow, spleen T cell phenotype may additionally involve lymph nodes, liver, skin (20%) (T cell prolymphocytic leukemia involving extramedullary sites, Am J Clin Pathol 2005;123:456 ) Pathophysiology[pathologyoutlines.com]

Prevention

  • BACKGROUND: Scarce systematic trial data have prevented uniform therapeutic guidelines for T-cell prolymphocytic leukemia (T-PLL).[ncbi.nlm.nih.gov]
  • Patients With Cancer Completed NCT00661999 Phase 3 sodium ferric gluconate complex in sucrose 9 Fentanyl Sublingual Spray in Treating Patients With Breakthrough Cancer Pain Completed NCT00538850 Phase 3 Fentanyl sublingual spray;Placebo 10 Dalteparin to Prevent[malacards.org]
  • Once in the blood, leukemia cells can spread to other organs, where they can prevent other cells in the body from functioning normally.[cancer.org]
  • Am J Hum Genet 1998, 62: 334–335. 10.1086/301706 PubMed Central PubMed View Article Google Scholar Friedenson B: The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers.[ehoonline.biomedcentral.com]

References

Article

  1. Dearden C. How I treat prolymphocytic leukemia. Blood. 2012;120(3):538-551.
  2. Matutes E, Brito-Babapulle V, Swansbury J, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukaemia. Blood. 1991;78(12):3269-3274.
  3. van der Velden VH, Hoogeveen PG, de Ridder D, et al. B-cell prolymphocytic leukemia: a specific subgroup of mantle cell lymphoma. Blood. 2014;17;124(3):412-419.
  4. Graham RL, Cooper B, Krause JR. T-cell prolymphocytic leukemia. Proc (Bayl Univ Med Cent). 2013;26(1):19-21.
  5. Soma L, Cornfield DB, Prager D, Nowell P, Bagg A. Unusually indolent T-cell prolymphocytic leukemia associated with a complex karyotype: is this T-cell chronic lymphocytic leukemia? Am J Hematol. 2002;71(3):224-226.
  6. Yoshioka Y, Nagao M, Saitoh T, et al. T-Cell Prolymphocytic Leukemia, Small Cell Variant, Possibly at the Stage of Intracytoplasmic Expression of CD3 in T-Cell Ontogenesis. J Clin Exp Hematop. 2015;55(1):17-21.
  7. Herling M, Patel KA, Teitell MA, et al. High TCL1 expression and intact T-cell receptor signaling define a hyperproliferative subset of T-cell prolymphocytic leukemia. Blood. 2008;111(1):328-337.

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Last updated: 2019-07-11 20:41