Purine Nucleoside Analogs Plus Rituximab Is an Effective Treatment Choice for Hairy Cell Leukemia-Variant: Results from a Single Center in China

Abstract Background: Hairy cell leukemia-variant (HCL-v) is one type of chronic lymphocytic proliferative disorders which was classified into splenic B-cell lymphoma/leukemia, unclassifiable. Both clinical and laboratory characteristics and treatment strategy remain elusive due to the rarity of the disease. Here, we firstly presented the diseases features and efficacy of a variety of treatment options in a large cohort from China. Methods: Thirty-three patients were diagnosed with HCL-v in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College from June 1990 to February 2021. We analyzed the disease characteristics and treatment outcome, especially in terms of clinical manifestation, immunophenotypic and molecular evaluation and efficacy of multiple first-line treatment. Results: The median age of this cohort was 59 years (range, 34-79 years) at diagnosis, with 23 males and 10 females. Abdominal mass and relative signs (n=22) and abnormal complete blood count (n=9) were the most common chief complaints. Splenomegaly was present in 32 (97.0%) cases, among whom 26 (78.8%) cases were massive. Leukocytosis and leukopenia were presented in 23 (69.7%) patients and 5 (15.2%) patients, with a median white blood cell count of 21.58×10 9/L (range, 1.34-224.59×10 9/L). The median percentage of the leukemic cells in bone marrow tested by flow cytometry was 33% (range, 6.2%-96%), and immunophenotyping showed monoclonal B-cells positive for pan B-cell antigens (CD19, CD20, CD22, CD79b) in almost all patients (Table). CD11c was positive in all patients, and CD103 was positive in 20/26 (76.9%) patients. CD25 was negative in 30/33 (90.9%) patients, and CD23 was negative in 20/26 (76.9%) cases. CD200 was frequently expressed among patients (15/21, 71.4%). For the pathological pattern of bone marrow involvement, 20/27 (74.1%) patients showed a predominantly interstitial pattern. Moreover, Annexin A1 was negative in all (n=12) patients detected by immunohistochemistry. Conventional cytogenetic analysis showed abnormal karyotype in 10/24 (41.7%) patients, including 6 patients with complex karyotype. Fluorescence in situ hybridization analysis showed deletion of TP53 in 4/20 (20.0%) patients and IGH translocation in 5/16 (31.3%) patients. The BRAF V600E mutation was negative in all the patients (n=20). In 2 of 14 (16.7%) patients, TP53 mutation was detected by next-generation sequencing. Sixteen of nineteen (84.2%) patients showed monoclonal IGHV rearrangements, and the most common rearrangement fragment was VH4-34 (n=3, 18.8%). Six of seventeen (35.3%) patients presented with unmutated IGHV and patients with VH4-34 were all unmutated. 31 patients needed treatment finally. Treatment choices included interferon-α (IFN-α) in 11 patients, chlorambucil (CLB) in 5 patients, single purine nucleoside analogs (PNA) in 3 patients and PNA plus rituximab in 9 patients. Four patients who received IFN-α or CLB treatment also underwent splenectomy. The objective response rate was 100% for patients receiving PNA plus rituximab and 77% for cases receiving others. And people treated with PNA plus rituximab had a higher complete response rate compared to the other regimen (75% versus 12%, P = 0.004). During a median follow-up of 32 months (range, 3-207) for 29 patients, 14 (48.3%) patients experienced at least one relapse or progression, and 7 (24.1%) patients had 2 or more relapses. Of note, one case also underwent a diffuse large B-cell lymphoma transformation. The median PFS and OS were 31 months (95% CI 25.5-36.5) and 70 months (95% CI 50.5-89.5), respectively. PNA plus rituximab prolong PFS compared to the others (3-year PFS rate 80% [95%CI 20-97] versus 10% [95%CI 1-35], P = 0.012, Figure A). But no significant difference in 3-year OS rate was observed between two groups (100% [95%CI 100-100] versus 43% [95%CI 10-73], P = 0.128, Figure B). Conclusion: HCL-v is a rare disease with specific clinical and immunophenotypic features but may overlap with classic hairy cell leukemia or other splenic B-cell neoplasms. Overall, it is an indolent lymphoma with recurrent progression, and the use of PNA plus rituximab in first-line treatment can result in a deeper and longer remission. Figure 1 Figure 1. Disclosures Wang: AbbVie: Consultancy; Astellas Pharma, Inc.: Research Funding.

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Antigenic phenotypes of hairy cell leukemia and monocytoid B-cell lymphoma: An immunohistochemical evaluation of 66 cases

Human Pathology ◽

10.1016/0046-8177(92)90239-y ◽

1992 ◽

Vol 23 (2) ◽

pp. 172-177 ◽

Cited By ~ 24

Author(s):

Robert Stroup ◽

Khalil Sheibani

Keyword(s):

B Cell ◽

Hairy Cell Leukemia ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Hairy Cell ◽

Cell Leukemia ◽

Monocytoid B Cell

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Lack of evidence of Epstein-Barr virus in hairy cell leukemia and monocytoid B-cell lymphoma

Human Pathology ◽

10.1016/0046-8177(93)90063-m ◽

1993 ◽

Vol 24 (1) ◽

pp. 58-61 ◽

Cited By ~ 7

Author(s):

Karen L. Chang ◽

Yuan-Yuan Chen ◽

Lawrence M. Weiss

Keyword(s):

B Cell ◽

Hairy Cell Leukemia ◽

Epstein Barr Virus ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Hairy Cell ◽

Cell Leukemia ◽

Barr Virus ◽

Epstein Barr ◽

Monocytoid B Cell

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CD5-Negative, CD10-Negative Low-Grade B-Cell Lymphoproliferative Disorders of the Spleen

Current Oncology ◽

10.3390/curroncol28060430 ◽

2021 ◽

Vol 28 (6) ◽

pp. 5124-5147

Author(s):

John J. Schmieg ◽

Jeannie M. Muir ◽

Nadine S. Aguilera ◽

Aaron Auerbach

Keyword(s):

Bone Marrow ◽

B Cell ◽

Hairy Cell Leukemia ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoproliferative Disorders ◽

Low Grade ◽

Hairy Cell ◽

Cell Leukemia ◽

Red Pulp

CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature B-cell proliferations that are essential to accurately identify but can be difficult to diagnose. They comprise the majority of B-cell LPDs primary to the spleen, commonly presenting with splenomegaly and co-involvement of peripheral blood and bone marrow, but with little to no involvement of lymph nodes. Splenic marginal zone lymphoma is one of the prototypical, best studied, and most frequently encountered CD5-CD10-LPD of the spleen and typically involves white pulp. In contrast, hairy cell leukemia, another well-studied CD5-CD10-LPD of the spleen, involves red pulp, as do the two less common entities comprising so-called splenic B-cell lymphoma/leukemia unclassifiable: splenic diffuse red pulp small B-cell lymphoma and hairy cell leukemia variant. Although not always encountered in the spleen, lymphoplasmacytic lymphoma, a B-cell lymphoproliferative disorder consisting of a dual population of both clonal B-cells and plasma cells and the frequent presence of the MYD88 L265P mutation, is another CD5-CD10-LPD that can be seen in the spleen. Distinction of these different entities is possible through careful evaluation of morphologic, immunophenotypic, cytogenetic, and molecular features, as well as peripheral blood and bone marrow specimens. A firm understanding of this group of low-grade B-cell lymphoproliferative disorders is necessary for accurate diagnosis leading to optimal patient management.

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A Unique Hairy Cell Leukemia Variant

Case Reports in Oncology ◽

10.1159/000446696 ◽

2016 ◽

Vol 9 (2) ◽

pp. 312-316

Author(s):

Charles Jian ◽

Cyrus C. Hsia

Keyword(s):

Flow Cytometry ◽

B Cell ◽

Hairy Cell Leukemia ◽

Nucleoside Analogs ◽

B Cell Lymphoma ◽

Purine Nucleoside ◽

Peripheral Blood Flow ◽

Hairy Cell ◽

Cell Leukemia ◽

Normal Peripheral Blood

A 65-year-old woman presented with easy bruising, left upper quadrant pain, decreased appetite, and weight loss. She had splenomegaly and lymphocytosis (lymphocyte count of 11.6 × 109/l), with remarkably abnormal appearing morphology. Her hemoglobin and platelet counts were normal. Peripheral blood flow cytometry revealed a monoclonal B-cell population expressing CD11c, CD25, CD19, CD20, and CD103. An initial diagnosis of hairy cell leukemia (HCL) was made, and the patient was treated with a standard 5-day course of cladribine. However, her lymphocytosis improved transiently, with a relapse 4 months later. There was no improvement in her splenomegaly. An HCL variant (HCL-v) was considered based on her resistance to treatment with a purine nucleoside analog. A subsequent splenectomy improved symptoms. Two years after, the patient suffered a relapse and underwent 6 cycles of CHOP-R (cyclophosphamide, hydroxydaunomycin, oncovin, prednisone, and rituximab), achieving partial remission. While under observation, she progressed with lymphocytosis 6 months later and was treated with pentostatin. There was no significant improvement in her disease, and she died 8 weeks following treatment initiation. HCL-v is a clinically more aggressive mature B-cell lymphoma than HCL with worse splenomegaly, higher lymphocyte counts, and resistance to typical HCL therapy with purine nucleoside analogs. Early recognition of HCL-v in the history, physical examination, and investigations with morphology and flow cytometry is key to patient management. Further, as in our case of HCL-v, cell morphology can be distinctly atypical, with large nucleoli and extremely convoluted nuclei. The distinction between HCL and HCL-v is important as HCL-v patients require more aggressive therapy and closer follow-up.

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Efficacy of Rituximab in Hairy Cell Leukemia.

Blood ◽

10.1182/blood.v108.11.4719.4719 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4719-4719

Author(s):

Styliani I. Kokoris ◽

Maria K. Angelopoulou ◽

Zacharoula I. Galani ◽

Konstantinos Anargyrou ◽

Sotirios Sachanas ◽

...

Keyword(s):

Bone Marrow ◽

Interferon Alpha ◽

Hairy Cell Leukemia ◽

Response Rate ◽

Costal Margin ◽

Line Treatment ◽

Hairy Cell ◽

Cell Leukemia ◽

First Line ◽

First Line Treatment

Abstract BACKGROUND: Hairy Cell Leukemia (HCL) is a rare B-chronic lymphoproliferative disorder (BCLD) with an indolent course. First-line treatment modalities include 2-chlorodeoxyadenosine (2-CDA), 2-deoxycoformycin (2-DCF) and interferon-alpha. The efficacy of anti-CD20-Rituximab (R) in other BCLDs, as well as strong CD20 expression by HCL cells, indicate that R could be an alternative treatment of HCL. AIMS: The experience of a single Hematology Unit in the treatment of relapsed HCL with R. PATIENTS AND METHODS: We retrospectively analyzed all HCL patients (pts) who received R as salvage therapy in 1st or subsequent relapse. RESULTS: 13 patients treated with R were located among 110 patients diagnosed with HCL between 1980 and 2005. 11 were males and their median age before R treatment was 46 years (range: 42–88). 5 pts had splenomegaly with a median spleen size of 7cm below left costal margin (range:5–20cm). 3 pts has an absolute neutrophil count<1.5×109/L, 4 a hemoglobin <10g/dL and 5pts a platelet count<100×109/L. All patients displayed a typical immunophenotype from blood and/or bone marrow (CD20 strongly +, CD19+, CD22+, FMC-7+, CD11c+, CD25+, CD103+). Four of them were CD23+ and two CD10+. 8 pts received Rituximab at 1st relapse. Among them, one had received 2-DCF as first-line treatment, one 2-CDA and 6 interferon-alpha as induction and maintenance. 3 pts had received more than one prior treatments. Two pts received R at diagnosis, due to older age. The median time from diagnosis to R initiation was 61 months (range: 4–275). R was administered at 375mg/m2 weekly for 6 cycles. Overall response rate was 67%, with 4 pts showing a negative immunophenotype. One pt discontinued treatment after the first cycle due to the development of thrombocytopenia that was attributed to the drug. 7/8 responders showed a complete restoration of their cytopenias. No other complications were recorded, except of mild infusion-related symptoms. Among the responding pts, none has relapsed so far with a median follow-up of 14 months (range: 4–40+). Among partial responders, one achieved a complete response including a negative bone marrow and immunophenotype after R retreatment. CONCLUSIONS: R is a highly effective and tolerable treatment for HCL in relapse with a response rate of 67%. Retreatment or maintenance with R may be important, since ongoing responses are seen.

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