Asymptomatic T prolymphocytic leukemia: case report and literature review

Honorato Junior, Luiz Frederico Bezerra; Souto, Elizabeth Xisto; Safranauskas, Roberta Maria da Silva Oliveira; Kishimoto, Renata Kiyomi; Bento, Laiz Cameirao; Passaro, Marilia Sandoval; Kojima, Rodrigo Seiti; Bacal, Nydia Strachman; Galvão, Barbara Ferreira Cordeiro; Cortês, Luiz Gustavo Ferreira; Velloso, Elvira Deolinda Rodrigues Pereira; Hamershlak, Nelson

doi:10.31744/einstein_journal/2025RC1899

ABSTRACT

T-cell prolymphocytic leukemia is a rare and aggressive mature T-cell malignancy that usually presents with marked lymphocytosis, hepatosplenomegaly, lymphadenopathy, and B symptoms. However, a minority of patients present with an indolent, asymptomatic form. Case Report: A 44-year-old man was diagnosed with asymptomatic T-cell prolymphocytic leukemia after routine blood tests revealed persistent lymphocytosis. Immunophenotyping revealed a mature CD4^-/CD8⁺ T-cell population. Cytogenetic analysis showed 14q11.2 abnormalities with TCRAD rearrangement by fluorescent in situ hybridization. A monoclonal T-cell population was confirmed by flow cytometry and polymerase chain reaction, and a STAT5B mutation was identified by next-generation sequencing. The patient had no cytopenia or organ involvement and a watch-and-wait strategy was adopted. The pathogenesis of T-cell prolymphocytic leukemia involves recurrent genetic alterations, including TCL1A rearrangements and ATM mutations, which promote genomic instability. Despite their aggressive nature, up to 30% of cases initially follow an indolent course, allowing for observation rather than immediate treatment. Standard therapies include alemtuzumab-based regimens and hematopoietic stem cell transplantation, although relapse rates remain high. Conclusion: This case underscores the need to recognize indolent presentations of T-cell prolymphocytic leukemia that may be managed conservatively. Further research is required to identify prognostic markers and optimize therapeutic strategies.

Keywords:
Leukemia, prolymphocytic, T-cell; T-Lymphocytes; Asymptomatic diseases

INTRODUCTION

T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic malignancy that accounts for approximately 2% of mature lymphoid neoplasms and was first described in 1973. It is characterized by the clonal proliferation of small- to medium-sized prolymphocytes with a mature post-thymic T-cell phenotype, typically involving the juxtaposition of TCL1A or MTCP1 at the T-cell receptor locus.(¹–²)

T-cell prolymphocytic leukemia typically presents with marked lymphocytosis (>100,000/μL), anemia, thrombocytopenia, hepatosplenomegaly, generalized, nonbulky lymphadenopathy, and B symptoms. Additional manifestations may include skin involvement, serous effusions (pleural, peritoneal), and more rarely, central nervous system involvement, with the latter occurring in only approximately 10% of patients. The skin is the most commonly affected extramedullary site and is often associated with a high tumor burden.(²–⁴)

The median interval from diagnosis to treatment initiation is typically approximately two months.(²,⁵–⁷) Approximately 30% of patients initially present with an indolent and asymptomatic phase, which often progresses to active disease within 1-2 years.

With an estimated incidence of 0.6-2 cases per million annually, the disease primarily affects adults aged over 30 years, with a median age of 65 years.(⁴) Due to its rarity, the characterization of clinical subtypes and therapeutic strategies remains limited, with most data derived from case reports or small series.

This manuscript describes a case of asymptomatic T-PLL with minimal laboratory abnormalities that did not require immediate treatment. Reporting rare presentations is essential to broaden our understanding of this rare disease and its clinical heterogeneity.

CASE REPORT

A 44-year-old man with a history of lymphocytosis that developed in June 2021 was referred for evaluation after routine blood tests revealed progressive leukocytosis. The patient remained asymptomatic with no cytopenia and a lymphocyte count of 8,000/mm³ (Figure 1A).

Figure 1
Morphologic, immunophenotypic, cytogenetic, and molecular features of indolent T-cell prolymphocytic leukemia at diagnosis

Peripheral blood immunophenotyping revealed 62.7% abnormal, monoclonal T lymphoid cells, expressing CD2 (partial), CD3, CD5, CD7, CD8, CD26, and T-cell receptor (TCR) α/β, and negative for CD4, CD30, CD56, and TCR γ/δ. Monoclonality was confirmed by flow cytometry for TRBC1 antigen expression (Figure 1B), and clonal TCR rearrangement was confirmed by reverse transcription polymerase chain reaction.

Positron emission tomography-computed tomography revealed no abnormal glycolytic hypermetabolism or visceromegaly. Cytogenetic and molecular analyses were then performed. Unstimulated peripheral blood metaphase showed a complex karyotype, including a translocation between the long arms of chromosome 14 and its homolog (Figure 1C). Fluorescent in situ hybridization with a TCRAD Break Apart probe (MetaSystems^®, Germany) confirmed TCRAD gene rearrangement on chromosome 14, with additional 5′ TCRAD copies in a marker chromosome (Figure 1D).

Molecular analysis identified a pathogenic STAT5B mutation (c.1924A>C, p.Asn642His) with a variant allele frequency of 13.9% along with a germline heterozygous pathogenic variant in MLH1 (c.1731G>A, p.Ser577=), which was confirmed as a germline mutation in a fibroblast culture after a skin biopsy.

The diagnosis of T-PLL was based on the presence of clonal lymphocytosis >5×10⁹/L, T-cell clonality, TCRAD rearrangement, and STAT5B mutation. The patient remained completely asymptomatic without cytopenia or other hematologic abnormalities, and active surveillance was initiated.

This case study was approved by the Research Ethics Committee of Hospital Israelita Albert Einstein (CAAE: 57507322.6.0000.0071; # 5.716.523), and written informed consent was obtained from the patient.

DISCUSSION

The pathogenesis of T-PLL involves rearrangement of the TCR, located on chromosome 14q) and juxtaposition with T-cell leukemia (TCL) genes, leading to the aberrant expression of TCL1A, TCL1B, or MTCP1 oncogenes in approximately 95% of cases. ATM involvement and genomic instability, due to deletions or mutations that impair DNA repair mechanisms, have also been reported, albeit less frequently. Mutations in the JAK1, JAK3, and STAT5B pathways (as observed in our case) are common, resulting in constitutive activation of cellular growth signaling.(¹,³,⁷,¹³) Additional alterations include mutations in EZH2, FBXW10, and CHEK2. Cytogenetically, inv(14)(q11q32) or t(14;14)(q11;q32) and chromosome 8 abnormalities are frequent, with the latter leading to increased C-MYC expression and accelerated proliferation.(¹–⁵,⁷,⁸)

Diagnosis is typically established through analysis of the peripheral blood or bone marrow. However, a bone marrow biopsy is often unnecessary as the diagnosis can generally be confirmed through peripheral blood examination.(²,⁵,⁸,⁹) Although most patients present with aggressive features, approximately 30% show an indolent, asymptomatic course, with a median time to progression of 1-2 years, and occasional reports of progression of up to 4 years.(¹⁰)

Diagnostic criteria include T-cell lymphocytosis >5×10⁹/L, a T-PLL immunophenotype in peripheral blood or bone marrow, and clonal T-cell population confirmed by polymerase chain reaction or flow cytometry, in association with chromosome 14 abnormalities or overexpression of TCL1 or MTCP1. Alternatively, if the first two major criteria are satisfied, a diagnosis can be established using at least one minor criterion.(⁴)

T-cell prolymphocytic leukemia presents with three morphological variants. The most common type (50-75% of cases) consists of small- to medium-sized lymphocytes with a high nuclear-to-cytoplasmic ratio, condensed chromatin, and a single prominent nucleolus. The second group (20-25% of cases) has atypical lymphocytes with convoluted nuclei, resembling Sézary cells. The third variant is characterized by small atypical lymphocytes that mimic chronic lymphocytic leukemia.(²) The immunophenotype corresponds to post-thymic mature T-cells, typically TdT and CD1a negative, and CD3 positive. The most frequent phenotype is CD4⁺/CD8^– (40-60%), followed by CD4⁺/CD8⁺ (25-41%) and CD4^–/CD8⁺ (15%). CD52 is commonly expressed, making it therapeutically relevant. The most common TCR is αβ.(¹¹,¹²) Our patient had the rare CD4^–/CD8⁺ phenotype with gamma-delta TCR expression.

One of the largest T-PLL studies included 119 patients (75 untreated and 43 previously treated) between 1990 and 2016, with a mortality rate of 80%. Poor prognostic indicators included pleural effusion, TCL1 positivity, leukocytosis >200,000/μL, anemia, elevated LDH (>1669IU/L), and non-Caucasian ethnicity. A complex karyotype is observed in up to 80% of the cases and is considered a negative prognostic factor. Other poor prognostic factors include an age older than 65 years, serous effusion, central nervous system or hepatic involvement, bulky lymphadenopathy, high TCL1 expression, bone marrow failure, and organ dysfunction.(¹,⁷,¹³–¹⁵)

The main differential diagnoses were adult T-cell leukemia/lymphoma, Sézary syndrome, large granular lymphocytic leukemia, T/B-cell acute lymphoblastic leukemia, hepatosplenic lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. Diagnosis requires integration of clinical presentation, immunophenotyping, and cytogenetics.

There is no solid evidence to support the early treatment of asymptomatic patients. Patients who respond poorly to chemotherapy should be managed based on clinical observations. The T-PLL International Study Group (TPLL-ISG) recommends initiating therapy in patients with fatigue, B symptoms, bone marrow failure, symptomatic adenopathy, hepatosplenomegaly, rapidly increasing lymphocytosis, or significant extranodal involvement.(⁴,¹²)

Most chemotherapy regimens are based on CHOP or FMC, yielding complete responses lasting only 3-6 months, and a median overall survival of 8-9 months.(²,⁶,¹⁰,¹²) Better outcomes were associated with the use of nonchemotherapeutic agents. Pentostatin, an ADA-inhibiting antimetabolite, has shown modest efficacy, either as a monotherapy or in combination. In responders, the overall survival can reach 16-18 months, although the responses are typically short, with a median duration of six months.(⁶,¹⁰,¹²)

Alemtuzumab, a monoclonal antibody against CD52, has shown the most promising clinical response in T-PLL, whether administered as induction, monotherapy, combination, salvage, or maintenance therapy. It is generally well tolerated with manageable side effects, including infusion reactions, lymphopenia, and infections.(¹⁵–¹⁹) The intravenous formulation resulted in higher response and survival rates than the subcutaneous version.(¹⁷,¹⁸, ²⁰)

A retrospective study of 119 patients showed that 55 previously untreated patients received alemtuzumab-based regimens with 42 receiving monotherapy and 13 receiving alemtuzumab in combination with pentostatin. The overall response and complete response rates for alemtuzumab alone were 83% and 66%, respectively, and those for combination therapy were 82% and 73%, respectively. In a phase II study involving 13 patients, the overall response rate, progression-free survival, and overall survival rates were 69%, 8 months, and 10 months, respectively, with alemtuzumab plus pentostatin.(⁷,¹⁵)

Alemtuzumab also demonstrated utility as a salvage therapy, with a study of 37 previously treated patients reporting an overall response rate of 76% and a median overall survival of 10 months.(¹⁶,²¹) It can be used for maintenance therapy after chemotherapy to improve responses in patients who are not initially eligible.(¹⁸,¹⁹)

Given the aggressiveness of T-PLL, remission is often short and relapse is common. Allogeneic stem cell transplantation should be considered for patients who achieve a complete response, particularly as first-line therapies. Autologous transplantation may be an option in cases without a suitable donor or in those who are ineligible for allogeneic transplantation. One-to-four-year survival rates range from 20-40%, with transplant-related mortality and relapse rates of approximately 30-40%.(²¹–²⁷)

CONCLUSION

T-cell prolymphocytic leukemia is a rare disease that typically presents aggressively and is associated with a high risk of relapse. In symptomatic cases, treatment is based on immunotherapy, either alone or in combination, followed by allogeneic hematopoietic stem cell transplantation during the first remission. However, this strategy is associated with high morbidity and frequent relapse, emphasizing the limitations of the current treatments.

Our patient belonged to the indolent subgroup, remained asymptomatic, and did not require immediate treatment. The selected strategy was based on clinical observations. Due to its rarity, increasing awareness through case reports and discussions is essential to stimulate debate and enhance our understanding of this challenging malignancy.

REFERENCES

¹ Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IB, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720-48. Erratum in: Leukemia. 2023;37(9):1944-51.
² Gutierrez M, Bladek P, Goksu B, Murga-Zamalloa C, Bixby D, Wilcox R. T-cell prolymphocytic leukemia: Diagnosis, pathogenesis, and treatment. Int J Mol Sci. 2023;24(15):12106.
³ Herling M, Valbuena JR, Jones D, Medeiros LJ. Envolvimento da pele na leucemia prolinfocítica de células T. J Am Acad Dermatol. 2007;57(3):533-4.
⁴ Hsi AC, Robirds DH, Luo J, Kreisel FH, Frater JL, Nguyen TT. Leucemia prolinfocítica de células T frequentemente mostra envolvimento cutâneo e está associada a ganhos de MYC, perda de ATM e rearranjo de TCL1A. Am J Surg Pathol. 2014;38(11):1468-83.
⁵ Staber PB, Herling M, Bellido M, Jacobsen ED, Davids MS, Kadia TM, et al. Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia. Blood. 2019;134(14):1132-43.
⁶ Matutes E, Brito-Babapulle V, Swansbury J, Ellis J, Morilla R, Dearden C, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood. 1991;78(12):3269-74.
⁷ Jain P, Aoki E, Keating M, Wierda WG, O’Brien S, Gonzalez GN, et al. Characteristics, outcomes, prognostic factors and treatment of patients with T-cell prolymphocytic leukemia (T-PLL). Ann Oncol. 2017;28(7):1554-9.
⁸ Campo E, Jaffe ES, Cook JR, Quintanilla-Martinez L, Swerdlow SH, Anderson KC, et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. Blood. 2022;140(11):1229-53.
⁹ Hu Z, Li S, Medeiros LJ, Sun T. TCL-1-positive hematogones in a patient with T-cell prolymphocytic leukemia after therapy. Hum Pathol. 2017;65:175-9.
¹⁰ Mercieca J, Matutes E, Dearden C, MacLennan K, Catovsky D. The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype. J Clin Oncol. 1994;12(12):2588-93.
¹¹ Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Dyer MJ, et al. Níveis de expressão de CD52 em células B e T normais e leucêmicas: correlação com respostas terapêuticas in vivo ao Campath-1H. Leuk Res. 1998;22(2):185-91.
¹² Horwitz SM, Ansell S, Ai WZ, Barnes J, Barta SK, Brammer J, et al. T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(3):285-308.
¹³ Braun T, Glass M, Wahnschaffe L, Otte M, Mayer P, Franitza M, et al. Micro-RNA networks in T-cell prolymphocytic leukemia reflect T-cell activation and shape DNA damage response and survival pathways. Haematologica. 2022;107(1):187-200.
¹⁴ Herling M, Patel KA, Teitell MA, Konopleva M, Ravandi F, Kobayashi R, et al. High TCL1 expression and intact T-cell receptor signaling define a hyperproliferative subset of T-cell prolymphocytic leukemia. Blood. 2008;111(1):328-37.
¹⁵ Ravandi F, Aribi A, O’Brien S, Faderl S, Jones D, Ferrajoli A, et al. Phase II study of alemtuzumab in combination with pentostatin in patients with T-cell neoplasms. J Clin Oncol. 2009;27(32):5425-30.
¹⁶ Dearden CE, Matutes E, Cazin B, Tjønnfjord GE, Parreira A, Nomdedeu B, et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood. 2001;98(6):1721-6.
¹⁷ Dearden CE, Khot A, Else M, Hamblin M, Grand E, Roy A, et al. Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route. Blood. 2011;118(22):5799-802.
¹⁸ Pflug N, Cramer P, Robrecht S, Bahlo J, Westermann A, Fink AM, et al. New lessons learned in T-PLL: results from a prospective phase-II trial with fludarabine-mitoxantrone-cyclophosphamide-alemtuzumab induction followed by alemtuzumab maintenance. Leuk Lymphoma. 2019;60(3):649-57.
¹⁹ Hopfinger G, Busch R, Pflug N, Weit N, Westermann A, Fink AM, et al. Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia. Cancer. 2013;119(12):2258-67.
²⁰ Damlaj M, Sulai NH, Oliveira JL, Ketterling RP, Hashmi S, Witzig T, et al. Impact of alemtuzumab therapy and route of administration in T-prolymphocytic leukemia: a single-center experience. Clin Lymphoma Myeloma Leuk. 2015;15(11):699-704.
²¹ Guillaume T, Beguin Y, Tabrizi R, Nguyen S, Blaise D, Deconinck E, et al. Allogeneic hematopoietic stem cell transplantation for T-prolymphocytic leukemia: a report from the French society for stem cell transplantation (SFGM-TC). Eur J Haematol. 2015;94(3):265-9.
²² Wiktor-Jedrzejczak W, Dearden C, de Wreede L, van Biezen A, Brinch L, Leblond V, Brune M, Volin L, Kazmi M, Nagler A, Schetelig J, de Witte T, Dreger P; EBMT Chronic Leukemia Working Party. Hematopoietic stem cell transplantation in T-prolymphocytic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation and the Royal Marsden Consortium. Leukemia. 2012;26(5):972-6.
²³ Dholaria BR, Ayala E, Sokol L, Nishihori T, Chavez JC, Hussaini M, et al. Allogeneic hematopoietic cell transplantation in T-cell prolymphocytic leukemia: a single-center experience. Leuk Res. 2018;67:1-5.
²⁴ Yamasaki S, Nitta H, Kondo E, Uchida N, Miyazaki T, Ishiyama K, et al. Effect of allogeneic hematopoietic cell transplantation for patients with T-prolymphocytic leukemia: a retrospective study from the Adult Lymphoma Working Group of the Japan Society for hematopoietic cell transplantation. Ann Hematol. 2019;98(9):2213-20.
²⁵ Wiktor-Jedrzejczak W, Drozd-Sokolowska J, Eikema DJ, Hoek J, Potter M, Wulf G, et al. EBMT prospective observational study on allogeneic hematopoietic stem cell transplantation in T-prolymphocytic leukemia (T-PLL). Bone Marrow Transplant. 2019;54(9):1391-8.
²⁶ Rose A, Zhang L, Jain AG, Poovathukaran Babu A, Sokol L, Saeed H, et al. Delineation of clinical course, outcomes, and prognostic factors in patients with T-cell prolymphocytic leukemia. Am J Hematol. 2023;98(6):913-21.
²⁷ Murthy HS, Ahn KW, Estrada-Merly N, Alkhateeb HB, Bal S, Kharfan-Dabaja MA, et al. Outcomes of allogeneic hematopoietic cell transplantation in T-cell prolymphocytic leukemia: A contemporary analysis from the Center for International Blood and Marrow Transplant Research. Transplant Cell Ther. 2022;28(4):187.e1-10.

Edited by

Associate Editor:
Marcos de Lima The Ohio State University – Columbus, OH, USA ORCID: https://orcid.org/0000-0002-8568-4522

Publication Dates

Publication in this collection
17 Nov 2025
Date of issue
2025

History

Received
24 May 2025
Accepted
23 June 2025

This content is licensed under a Creative Commons Attribution 4.0 International License.

[1] ¹ Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IB, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720-48. Erratum in: Leukemia. 2023;37(9):1944-51.

[2] ² Gutierrez M, Bladek P, Goksu B, Murga-Zamalloa C, Bixby D, Wilcox R. T-cell prolymphocytic leukemia: Diagnosis, pathogenesis, and treatment. Int J Mol Sci. 2023;24(15):12106.

[3] ³ Herling M, Valbuena JR, Jones D, Medeiros LJ. Envolvimento da pele na leucemia prolinfocítica de células T. J Am Acad Dermatol. 2007;57(3):533-4.

[4] ⁴ Hsi AC, Robirds DH, Luo J, Kreisel FH, Frater JL, Nguyen TT. Leucemia prolinfocítica de células T frequentemente mostra envolvimento cutâneo e está associada a ganhos de MYC, perda de ATM e rearranjo de TCL1A. Am J Surg Pathol. 2014;38(11):1468-83.

[5] ⁵ Staber PB, Herling M, Bellido M, Jacobsen ED, Davids MS, Kadia TM, et al. Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia. Blood. 2019;134(14):1132-43.

[6] ⁶ Matutes E, Brito-Babapulle V, Swansbury J, Ellis J, Morilla R, Dearden C, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood. 1991;78(12):3269-74.

[7] ⁷ Jain P, Aoki E, Keating M, Wierda WG, O’Brien S, Gonzalez GN, et al. Characteristics, outcomes, prognostic factors and treatment of patients with T-cell prolymphocytic leukemia (T-PLL). Ann Oncol. 2017;28(7):1554-9.

[8] ⁸ Campo E, Jaffe ES, Cook JR, Quintanilla-Martinez L, Swerdlow SH, Anderson KC, et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. Blood. 2022;140(11):1229-53.

[9] ⁹ Hu Z, Li S, Medeiros LJ, Sun T. TCL-1-positive hematogones in a patient with T-cell prolymphocytic leukemia after therapy. Hum Pathol. 2017;65:175-9.

[10] ¹⁰ Mercieca J, Matutes E, Dearden C, MacLennan K, Catovsky D. The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype. J Clin Oncol. 1994;12(12):2588-93.

[11] ¹¹ Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Dyer MJ, et al. Níveis de expressão de CD52 em células B e T normais e leucêmicas: correlação com respostas terapêuticas in vivo ao Campath-1H. Leuk Res. 1998;22(2):185-91.

[12] ¹² Horwitz SM, Ansell S, Ai WZ, Barnes J, Barta SK, Brammer J, et al. T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(3):285-308.

[13] ¹³ Braun T, Glass M, Wahnschaffe L, Otte M, Mayer P, Franitza M, et al. Micro-RNA networks in T-cell prolymphocytic leukemia reflect T-cell activation and shape DNA damage response and survival pathways. Haematologica. 2022;107(1):187-200.

[14] ¹⁴ Herling M, Patel KA, Teitell MA, Konopleva M, Ravandi F, Kobayashi R, et al. High TCL1 expression and intact T-cell receptor signaling define a hyperproliferative subset of T-cell prolymphocytic leukemia. Blood. 2008;111(1):328-37.

[15] ¹⁵ Ravandi F, Aribi A, O’Brien S, Faderl S, Jones D, Ferrajoli A, et al. Phase II study of alemtuzumab in combination with pentostatin in patients with T-cell neoplasms. J Clin Oncol. 2009;27(32):5425-30.

[16] ¹⁶ Dearden CE, Matutes E, Cazin B, Tjønnfjord GE, Parreira A, Nomdedeu B, et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood. 2001;98(6):1721-6.

[17] ¹⁷ Dearden CE, Khot A, Else M, Hamblin M, Grand E, Roy A, et al. Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route. Blood. 2011;118(22):5799-802.

[18] ¹⁸ Pflug N, Cramer P, Robrecht S, Bahlo J, Westermann A, Fink AM, et al. New lessons learned in T-PLL: results from a prospective phase-II trial with fludarabine-mitoxantrone-cyclophosphamide-alemtuzumab induction followed by alemtuzumab maintenance. Leuk Lymphoma. 2019;60(3):649-57.

[19] ¹⁹ Hopfinger G, Busch R, Pflug N, Weit N, Westermann A, Fink AM, et al. Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia. Cancer. 2013;119(12):2258-67.

[20] ²⁰ Damlaj M, Sulai NH, Oliveira JL, Ketterling RP, Hashmi S, Witzig T, et al. Impact of alemtuzumab therapy and route of administration in T-prolymphocytic leukemia: a single-center experience. Clin Lymphoma Myeloma Leuk. 2015;15(11):699-704.

[21] ²¹ Guillaume T, Beguin Y, Tabrizi R, Nguyen S, Blaise D, Deconinck E, et al. Allogeneic hematopoietic stem cell transplantation for T-prolymphocytic leukemia: a report from the French society for stem cell transplantation (SFGM-TC). Eur J Haematol. 2015;94(3):265-9.

[22] ²² Wiktor-Jedrzejczak W, Dearden C, de Wreede L, van Biezen A, Brinch L, Leblond V, Brune M, Volin L, Kazmi M, Nagler A, Schetelig J, de Witte T, Dreger P; EBMT Chronic Leukemia Working Party. Hematopoietic stem cell transplantation in T-prolymphocytic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation and the Royal Marsden Consortium. Leukemia. 2012;26(5):972-6.

[23] ²³ Dholaria BR, Ayala E, Sokol L, Nishihori T, Chavez JC, Hussaini M, et al. Allogeneic hematopoietic cell transplantation in T-cell prolymphocytic leukemia: a single-center experience. Leuk Res. 2018;67:1-5.

[24] ²⁴ Yamasaki S, Nitta H, Kondo E, Uchida N, Miyazaki T, Ishiyama K, et al. Effect of allogeneic hematopoietic cell transplantation for patients with T-prolymphocytic leukemia: a retrospective study from the Adult Lymphoma Working Group of the Japan Society for hematopoietic cell transplantation. Ann Hematol. 2019;98(9):2213-20.

[25] ²⁵ Wiktor-Jedrzejczak W, Drozd-Sokolowska J, Eikema DJ, Hoek J, Potter M, Wulf G, et al. EBMT prospective observational study on allogeneic hematopoietic stem cell transplantation in T-prolymphocytic leukemia (T-PLL). Bone Marrow Transplant. 2019;54(9):1391-8.

[26] ²⁶ Rose A, Zhang L, Jain AG, Poovathukaran Babu A, Sokol L, Saeed H, et al. Delineation of clinical course, outcomes, and prognostic factors in patients with T-cell prolymphocytic leukemia. Am J Hematol. 2023;98(6):913-21.

[27] ²⁷ Murthy HS, Ahn KW, Estrada-Merly N, Alkhateeb HB, Bal S, Kharfan-Dabaja MA, et al. Outcomes of allogeneic hematopoietic cell transplantation in T-cell prolymphocytic leukemia: A contemporary analysis from the Center for International Blood and Marrow Transplant Research. Transplant Cell Ther. 2022;28(4):187.e1-10.