Beyond hairy cell: the activity of cladribine in other hematologic malignancies

Blood ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 2884-2896 ◽  
Author(s):  
Darren S. Sigal ◽  
Heather J. Miller ◽  
Ethan D. Schram ◽  
Alan Saven
Keyword(s):  
Hairy Cell Leukemia ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Full Spectrum ◽  
Lymphoid Malignancies ◽  
Duration Of Response ◽  
History Of ◽  
Contemporary Development

Abstract Before the contemporary development of rationally designed antineoplastic therapies, cladribine was identified as a lymphocyte-specific agent. Its profound impact on the natural history of hairy cell leukemia, with responses approaching 100% and a median duration of response of nearly a decade after only a single 7-day course, is well known and revolutionized the treatment of hairy cell leukemia. However, cladribine's impressive activity in other lymphoproliferative disorders has been generally underappreciated. Multiple single-arm phase 2 trials have demonstrated cladribine's potency across the full spectrum of lymphoid malignancies. In a limited number of phase 3 trials and cross-study analyses, cladribine compared favorably with fludarabine, another purine nucleoside analog that is more commonly used in the treatment of indolent lymphoid malignancies. Cladribine has been noted to have particular activity among lymphoid disorders with few effective therapies, specifically, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, marginal zone lymphoma, and mantle cell lymphoma. Recently approved novel agents may act in synergy with cladribine for these conditions and should be incorporated into future clinical studies.

scholarly journals Cell markers in hairy cell leukemia studied in cells from 51 patients

Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 52-60 ◽  
Author(s):  
J Jansen ◽  
HR Schuit ◽  
CJ Meijer ◽  
JA van Nieuwkoop ◽  
W Hijmans
Keyword(s):  
Heavy Chain ◽  
Hairy Cell Leukemia ◽  
Lymphocytic Leukemia ◽  
Mature Stage ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Neoplastic Cells ◽  
Hairy Cells ◽  
Immunoglobulin Levels ◽  
Chain Type

Abstract To determine the maturation arrest of the neoplastic cells of hairy- cell leukemia (HCL) and the spectrum of the surface markers on these cells, a series of 51 patients with this disease was studied. The cells of all but two of the patients showed monoclonal surface Ig with respect to light chains. In about one-third of the cases, only gamma heavy chain determinants were present on the cells; the majority carried multiple heavy chain determinants as documented by the application of different fluorochromes. Two patients each showed two different clones of cells, both of the same light chain type. In one of these two patients, two paraproteins were present in the serum. Intracytoplasmic Ig was found in only 4 of 39 cases, in all instances being IgM. All cases studied concerned cells with FclgG receptors; however, the density of this receptor varied. FcIgM receptors also showed a spectrum of density, with some cases showing very few FcIgM- positive cells. Receptors C3 were not observed on the hairy cells. Serum immunoglobulin levels were normal or increased. Paraproteins were found in the sera of 4 of 38 patients. These data suggest that HCL is a neoplasm of B lymphocytes. The neoplastic cells are probably arrested at a more mature stage than the cells of chronic lymphocytic leukemia. The multiple isotypes on the cells indicate a block at the “switch” phase from the small micro-carrying lymphocyte to the larger Ig- producing lymphocyte or plasma cell.

scholarly journals Monoclonal antibodies reactive with hairy cell leukemia [see comments]

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 320-325 ◽  
Author(s):  
L Visser ◽  
A Shaw ◽  
J Slupsky ◽  
H Vos ◽  
S Poppema
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Small Population ◽  
Lymphocytic Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Hairy Cells ◽  
A Minor ◽  
Insight Into

Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia. Antibody B-ly 2 can be considered a pan-B cell reagent and generally reacts similar to CD22 antibodies. Antibody B-ly 6 is reactive with the same antigen as CD11c (p150/95), an antigen that is present on hairy cell leukemia, macrophages, and a minor subpopulation of lymphocytes. Antibody B-ly 7 is a unique antibody reactive with 144 Kd antigen present only on hairy cell leukemia and a very small population of normal B lymphocytes. This subpopulation may be the counterpart of hairy cells.

scholarly journals Diffuse osteosclerosis in hairy cell leukemia

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2066-2069 ◽  
Author(s):  
LA VanderMolen ◽  
WJ Urba ◽  
DL Longo ◽  
J Lawrence ◽  
H Gralnick ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Interferon Alpha ◽  
Successful Treatment ◽  
Hairy Cell Leukemia ◽  
Malignant Disease ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Biopsies ◽  
Biopsy Needle ◽  
History Of

Abstract We describe two patients with a new clinical pathologic syndrome of diffuse osteosclerosis in association with hairy cell leukemia. In both patients bone marrow biopsies could not be obtained due to extremely hard bones and inability to insert the biopsy needle; neither patient had a history of bony pain or fracture. The osteosclerotic process in one patient stabilized after successful treatment of her hairy cell leukemia with interferon alpha and deoxycoformycin suggesting that the osteosclerosis observed was related to the underlying malignant disease. Possible etiologic mechanisms are discussed.

Involvement of CD44-hyaluronan interaction in malignant cell homing and fibronectin synthesis in hairy cell leukemia

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3161-3167 ◽  
Author(s):  
Khalil A. Aziz ◽  
Kathleen J. Till ◽  
Mirko Zuzel ◽  
John C. Cawley
Keyword(s):  
Hairy Cell Leukemia ◽  
Actin Polymerization ◽  
Malignant Cell ◽  
Lymphocytic Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Spontaneous Movement ◽  
Cell Adhesion And Migration ◽  
Cell Arrest ◽  
Hepatic Portal

Abstract The tissue homing of malignant hematic cells has both diagnostic and pathogenetic importance. Although such homing is incompletely understood, it generally involves cell adhesion and migration mediated by a number of adhesion receptors and cytokines. In this article, the potential importance of hyaluronan (HA) is examined for the tissue homing of hairy cells (HCs) in hairy cell leukemia (HCL). It is shown that HCs readily adhere to, and spontaneously move on, HA-coated surfaces using CD44. This indicates that activated CD44 and spontaneous movement on HA form part of the intrinsically activated phenotype of HCs. Interleukin-8 (IL-8) inhibited HC movement on HA, and this cell arrest was accompanied by increased actin polymerization and a more pronounced association of CD44 with the cytoskeleton. All of these findings are in sharp contrast to our previous observations with chronic lymphocytic leukemia cells, which are nonmotile on HA, but in response to IL-8 become polarized and motile using the receptor for HA-mediated motility rather than their apparently inactive CD44. Immunohistochemical examination of HCL tissues showed the ubiquitous presence of IL-8 and the prominence of HA in bone marrow stroma and hepatic portal tracts. This suggests that CD44-HA interactions are important in HC homing to these sites, but not to splenic red pulp or hepatic sinusoids, where HA is largely absent. Moreover, engagement of CD44 on HCs stimulates fibronectin synthesis, an observation that is likely to be relevant to the restriction of fibrosis in the disease to HC-infiltrated areas containing HA.

HSR19-086: Healthcare Costs and Resource Utilization Associated With Adverse Events Among Hairy Cell Leukemia Patients Treated With Purine Nucleoside Analogs

2019 ◽  
Vol 17 (3.5) ◽  
pp. HSR19-086
Author(s):  
Narendranath Epperla ◽  
Melissa Pavilack ◽  
Temitope Olufade ◽  
Richa Bashyal ◽  
Teng Huang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Resource Utilization ◽  
Hairy Cell Leukemia ◽  
Opportunistic Infections ◽  
Nucleoside Analogs ◽  
Purine Nucleoside ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
History Of

Background: Purine nucleoside analogs (PNAs) are highly effective for first-line treatment of hairy cell leukemia (HCL). In clinical trials of single PNAs, several adverse events (AEs) were reported; however, little is known regarding the costs and healthcare resource utilization (HRU) resulting from AEs in HCL patients (pts) treated with PNAs in non-clinical trial settings. Objective: Determine the costs and HRU of high incident and clinically important AEs associated with PNA therapy in HCL pts in the Truven MarketScan database. Methods: Adults (aged ≥18 years) with ≥2 HCL diagnosis codes ≥30 days apart during January 1, 2006–December 31, 2015 were included. Pts had ≥1 prescription claim for a PNA (cladribine or pentostatin ± rituximab) after HCL diagnosis date. First PNA claim date was defined as the index date. Pts had continuous health plan enrollment for ≥6 months at baseline and ≥12-months follow-up with no PNA in the baseline period. Pts were placed into cohorts based on the occurrence of myelosuppression (MSPN) and opportunistic infections (OI) as these were highest incident and clinically important AEs observed. Generalized linear models were used to compare outcomes during the 12-month follow-up. Results: Of the 219 pts with no history of MSPN, 101 developed MSPN (incidence [I]: 461 per 1000 pt-years) and of 619 pts with no history of OI, 26 developed OI (I: 42 per 1000 pt-years). Demographics were similar between pts with and without MSPN and OI. Pts who developed OI or MSPN had significantly higher inpatient admissions and costs (Table 1). Conclusions: PNA-treated HCL pts who developed MSPN or OI incurred higher HRU than those who did not develop either condition. This indicates the need for new therapeutic strategies to reduce HCL-treatment-associated toxicities.

The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1558-1562 ◽  
Author(s):  
E Matutes ◽  
R Morilla ◽  
K Owusu-Ankomah ◽  
A Houlihan ◽  
D Catovsky
Keyword(s):  
Differential Diagnosis ◽  
Monoclonal Antibodies ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Splenic Lymphoma ◽  
Weak Surface

Splenic lymphoma with villous lymphocytes (SLVL) is a low-grade disorder that regularly presents with peripheral blood involvement. We describe the immunophenotype of the circulating cells from 100 SLVL patients whose disease has been characterized on clinical, morphologic, and histologic grounds. Cells from all cases expressed B-cell antigens (CD19 and CD37) and/or HLA-Dr and showed light chain restriction (kappa/lambda: 1.5/1) with moderate to strong intensity of membrane Ig staining. Cells from most cases (> 80%) were CD24+, FMC7+, and expressed strongly membrane CD22. The monoclonal antibodies CD10, CD23, and CD38 were positive in one-third of the cases; CD11c in 47%; and CD25 in 25% of cases. A minority of cases (< 20%) were positive with HC2, B-ly-7, and CD5. However, none of the 19 CD5+ cases had the phenotype characteristic of chronic lymphocytic leukemia (CD5+, CD23+, FMC7-, weak surface Ig and membrane CD22). None of the 17 CD25+ cases had the immunophenotype typical of hairy cell leukemia (CD25+, CD11c+, HC2+, B-ly-7+). HC2 and B-ly-7 were the most useful reagents to distinguish SLVL from hairy cell leukemia. Our findings demonstrate that SLVL has a distinct immunologic profile and that monoclonal antibodies are important for the differential diagnosis between this disease and other B-lymphoproliferative disorders with which SLVL can be confused.

Trisomy 12 in Chronic Lymphocytic Leukemia and Hairy Cell Leukemia: A Cytogenetic and Interphase Cytogenetic Study

1994 ◽  
Vol 15 (1-2) ◽  
pp. 167-172 ◽  
Author(s):  
Antonio Cuneo ◽  
Renato Bigoni ◽  
Massimo Balboni ◽  
Maria Gretel Carli ◽  
Nadia Piva ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hairy Cell Leukemia ◽  
Cytogenetic Study ◽  
Lymphocytic Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Trisomy 12

scholarly journals Fludarabine and rituximab for relapsed or refractory hairy cell leukemia

Blood ◽  
2012 ◽  
Vol 119 (9) ◽  
pp. 1988-1991 ◽  
Author(s):  
Alina S. Gerrie ◽  
Leslie N. Zypchen ◽  
Joseph M. Connors
Keyword(s):  
Hairy Cell Leukemia ◽  
Therapeutic Option ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
First Line ◽  
Response Data ◽  
Purine Analog ◽  
Duration Of Response ◽  
Effective Therapeutic Option

Abstract The purine analogs, pentostatin and cladribine, induce high remission rates when used as first-line monotherapy for hairy cell leukemia (HCL); however, patients continue to relapse. Re-treatment with the same or alternate purine analog produces lower response rates and a shorter duration of response. Fludarabine is another purine analog widely used in indolent lymphoid cancers, often in combination with rituximab, but there are few reports of its use in HCL. We identified 15 patients treated in British Columbia with fludarabine and rituximab (FR) from 2004 to 2010 for relapsed/refractory HCL after first-line cladribine (n = 3) or after multiple lines of therapy (n = 12). All patients with available response data responded to FR. With median follow-up of 35 months, 14 patients remain progression-free, whereas 1 patient has developed progressive leukemia and died. Five-year progression-free and overall survivals are 89% and 83%, respectively. FR is a safe and effective therapeutic option for relapsed/refractory HCL.

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