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Leukemia & Lymphoma Dec 2019Hairy cell leukemia (HCL) is an indolent B-cell malignancy, with long-term responses to purine analogs, but with decreasing efficacy and increasing toxicity with... (Review)
Review
Hairy cell leukemia (HCL) is an indolent B-cell malignancy, with long-term responses to purine analogs, but with decreasing efficacy and increasing toxicity with repeated courses. Leukemic cells express CD22, CD20, CD25, tartrate-resistant acid phosphatase (TRAP), annexin 1A (Anxa1), and BRAF V600E mutation. HCLv, lacking CD25, Anxa1, TRAP, and BRAF V600E, is more aggressive and less purine analog-sensitive. A molecularly defined IGHV4-34+ variant is also resistant whether HCL or HCLv immunophenotypically. Traces of HCL cells, termed minimal residual disease (MRD), accompany most with complete remission (CR) and may cause relapse. Rituximab has limited single-agent activity, but frequent CR without MRD when combined with purine analog, albeit with chemotherapy toxicities. The anti-CD22 recombinant immunotoxin Moxetumomab Pasudotox can achieve MRD-negative CR in multiply relapsed HCL without chemotherapy toxicities and was FDA approved in 2018 as Lumoxiti. Investigational oral non-chemotherapy options also include Vemurafenib or Dabrafenib/Trametinib targeting BRAF V600E ± MEK, and Ibrutinib targeting Bruton's tyrosine kinase.
Topics: Algorithms; Biomarkers; Clinical Decision-Making; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Leukemia, Hairy Cell; Treatment Outcome
PubMed: 31068044
DOI: 10.1080/10428194.2019.1608536 -
Current Oncology Reports Aug 2023This article summarizes the current state of knowledge of hairy cell leukemia (HCL) regarding presentation, diagnosis, therapy, and monitoring, including perspectives on... (Review)
Review
PURPOSE OF REVIEW
This article summarizes the current state of knowledge of hairy cell leukemia (HCL) regarding presentation, diagnosis, therapy, and monitoring, including perspectives on emergent therapies.
RECENT FINDINGS
Over the past decade, there has been enormous progress in the understanding of the biology of HCL which has led to the development of novel therapeutic strategies. The maturation of data regarding existing management strategies has also lent considerable insight into therapeutic outcomes and prognosis of patients treated with chemo- or chemoimmunotherapy. Purine nucleoside analogs remain the cornerstone of treatment, and the addition of rituximab has deepened and prolonged responses in the upfront and relapsed setting. Targeted therapies now have a more defined role in the management of HCL, with BRAF inhibitors now having a potential in the first-line setting in selected cases as well as in relapse. Next-generation sequencing for the identification of targetable mutations, evaluation of measurable residual disease, and risk stratification continue to be areas of active investigation. Recent advances in HCL have led to more effective therapeutics in the upfront and relapsed setting. Future efforts will focus on identifying patients with high-risk disease who require intensified regimens. Multicenter collaborations are the key to improving overall survival and quality of life in this rare disease.
Topics: Humans; Leukemia, Hairy Cell; Antineoplastic Agents; Quality of Life; Rituximab; Prognosis; Multicenter Studies as Topic
PubMed: 37097545
DOI: 10.1007/s11912-023-01419-z -
Blood Feb 2017Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of...
Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.
Topics: Antineoplastic Agents; Cladribine; Disease Management; Humans; Leukemia, Hairy Cell; Neoplasm Recurrence, Local; Neoplasm, Residual; Pentostatin; Treatment Outcome
PubMed: 27903528
DOI: 10.1182/blood-2016-01-689422 -
Advances in Hematology 2023Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids,... (Review)
Review
BACKGROUND
Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids, which are ineffective in 30-50% of cases. Steroid-refractory GVHD (SR-GVHD) confers a poor prognosis, with high mortality rates despite appropriate therapy. While there is no reliable treatment for SR-GVHD, a variety of novel therapeutic options are slowly emerging and have yet to be examined simultaneously.
OBJECTIVES
This review evaluates the potential of novel therapeutic options, as well as their efficacy and safety, for the treatment of SR-GVHD. . The literature search was conducted in PubMed, Cochrane, and Embase, employing MeSH terms and keywords. The studies had to be prospective phases 1, 2, or 3. We excluded retrospective and nonoriginal studies.
RESULTS
While the only approved drug for acute GVHD is ruxolitinib with an impressive overall response rate of 73.2% and a complete response of 56.3%, several monoclonal antibodies and other agents are currently under investigation, offering promising results. These include anti-CD2, anti-CD147, IL-2 antagonist, a mixture of anti-CD3 and anti-CD7 antibodies, anti-CD25, monoclonal antibody to a4b7 on T-cells, anti-CD26, pentostatin, sirolimus, denileukin diftitox, infliximab, itacitinib, and alpha-1 antitripsin. However, the toxicities associated with these novel drugs need further investigation. For chronic GVHD, approved options include ruxolitinib with an ORR of up to 62%, ibrutinib with an ORR of up to 77%, and belumosudil with an ORR of up to 77%. Meanwhile, emerging treatments include tyrosine kinase inhibitors such as nilotinib, rituximab, and low-dose IL-2, as well as axatilimab and pomalidomide.
CONCLUSION
While their efficacy needs to be better evaluated through large-scale, multicenter, randomized clinical trials, these novel agents show potential and could provide a better alternative for SR-GVHD treatment in the future.
PubMed: 38094101
DOI: 10.1155/2023/9949961 -
Clinical Advances in Hematology &... Mar 2018Hairy cell leukemia (HCL) is a chronic B-cell malignancy with multiple treatment options, including several that are investigational. Patients present with pancytopenia... (Review)
Review
Hairy cell leukemia (HCL) is a chronic B-cell malignancy with multiple treatment options, including several that are investigational. Patients present with pancytopenia and splenomegaly, owing to the infiltration of leukemic cells expressing CD22, CD25, CD20, CD103, tartrate-resistant acid phosphatase (TRAP), annexin A1 (ANXA1), and the BRAF V600E mutation. A variant lacking CD25, ANXA1, TRAP, and the BRAF V600E mutation, called HCLv, is more aggressive and is classified as a separate disease. A molecularly defined variant expressing unmutated immunoglobulin heavy variable 4-34 (IGHV4-34) is also aggressive, lacks the BRAF V600E mutation, and has a phenotype of HCL or HCLv. The standard first-line treatment, which has remained unchanged for the past 25 to 30 years, is single-agent therapy with a purine analogue, either cladribine or pentostatin. This approach produces a high rate of complete remission. Residual traces of HCL cells, referred to as minimal residual disease, are present in most patients and cause frequent relapse. Repeated treatment with a purine analogue can restore remission, but at decreasing rates and with increasing cumulative toxicity. Rituximab has limited activity as a single agent but achieves high complete remission rates without minimal residual disease when combined with purine analogues, albeit with chemotherapy-associated toxicity. Investigational nonchemotherapy options include moxetumomab pasudotox, which targets CD22; vemurafenib or dabrafenib, each of which targets the BRAF V600E protein; trametinib, which targets mitogen-activated protein kinase enzyme (MEK); and ibrutinib, which targets Bruton tyrosine kinase (BTK).
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Biopsy; Clinical Decision-Making; Humans; Immunohistochemistry; Immunophenotyping; Leukemia, Hairy Cell; Molecular Targeted Therapy; Neoplasm, Residual; Standard of Care; Treatment Outcome
PubMed: 29742076
DOI: No ID Found -
Biomolecules Aug 2020Hairy cell leukemia (HCL) is an indolent B-cell malignancy with excellent initial response to purine analogs pentostatin or cladribine, but patients are rarely, if ever,... (Review)
Review
Hairy cell leukemia (HCL) is an indolent B-cell malignancy with excellent initial response to purine analogs pentostatin or cladribine, but patients are rarely, if ever, cured. Younger patients will usually need repeat chemotherapy which has declining benefits and increasing toxicities with each course. Targeted therapies directed to the BRAF V600E mutation and Bruton's tyrosine kinase may be helpful, but rarely eradicate the minimal residual disease (MRD) which will eventually lead to relapse. Moxetumomab pasudotox (Moxe) is an anti-CD22 recombinant immunotoxin, which binds to CD22 on HCL cells and leads to apoptotic cell death after internalization and trafficking of the toxin to the cytosol. Phase I testing achieved a complete remission (CR) rate of 57% in relapsed/refractory HCL. Most CRs were without MRD and eradication of MRD correlated with prolonged CR duration. Patients were often MRD-free after five years. Important mild-moderate toxicities included capillary leak and hemolytic uremic syndromes which could be prevented and managed conservatively. A phase 3 trial met its endpoint of durable CR with acceptable toxicity, leading to FDA approval of Moxe for relapsed/refractory HCL, under the name Lumoxiti. Moxe combined with rituximab is currently being evaluated in relapsed/refractory HCL to improve the rate of MRD-free CR.
Topics: Animals; Antineoplastic Agents, Immunological; Bacterial Toxins; Clinical Trials as Topic; Drug Development; Humans; Immunotoxins; Leukemia, Hairy Cell; Protein Engineering
PubMed: 32756468
DOI: 10.3390/biom10081140