The Role of Interferon Alpha in the Treatment of Hairy Cell Leukemia (HCL)

1988 ◽  
pp. 121-126
Author(s):  
J. R. Quesada
2006 ◽  
Vol 77 (2) ◽  
pp. 109-113 ◽  
Author(s):  
Giuseppe Marotta ◽  
Antonio Frassoldati ◽  
Pierluigi Zinzani ◽  
Luciana Annino ◽  
Maura Brugiatelli ◽  
...  

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2203-2209 ◽  
Author(s):  
MS Tallman ◽  
D Hakimian ◽  
D Variakojis ◽  
D Koslow ◽  
GA Sisney ◽  
...  

Abstract Twenty-six patients with hairy cell leukemia (HCL) were treated with 2- chlorodeoxyadenosine (2-CdA), a purine analogue resistant to adenosine deaminase, at 0.1 mg/kg/d for 7 days by continuous intravenous infusion. Fifteen patients were previously untreated, while 11 patients had received prior treatment with splenectomy alone (three patients), interferon alpha alone (four), splenectomy, then interferon alpha (two), or splenectomy, interferon alpha, then 2-deoxycoformycin (2-DCF) (two). Sixteen (80%) of 20 patients evaluable at 3 months achieved complete remission (CR), and four (20%) achieved partial remission (PR) following a single cycle of therapy. All four patients in PR had complete recovery of their peripheral blood counts (except one patient whose platelet count remained 84,000/microL), but had residual HCL in the bone marrow (three patients) or residual splenomegaly (one). Patients with bulky adenopathy, massive splenomegaly, and severe pancytopenia responded as well as those with only modest marrow involvement. The three patients with residual marrow disease received a second cycle of 2-CdA, and two have attained CR. Therefore, 18 of 20 (90%) achieved CR with either one or two cycles of therapy. No patient achieving CR has relapsed at a median follow-up of 12 (+/- 2.1) months. Toxicities included myelosuppression and culture-negative fever. A community-acquired pneumonia was the only infectious complication. Since a single cycle of 2-CdA induces sustained CR in the vast majority of patients with minimal toxicity, this agent is emerging as the treatment of choice for all patients with HCL.


Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2066-2069 ◽  
Author(s):  
LA VanderMolen ◽  
WJ Urba ◽  
DL Longo ◽  
J Lawrence ◽  
H Gralnick ◽  
...  

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.


Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 38-43 ◽  
Author(s):  
P von Wussow ◽  
H Pralle ◽  
HK Hochkeppel ◽  
D Jakschies ◽  
S Sonnen ◽  
...  

Abstract To explore the relationship between anti-interferon-alpha (anti-IFN- alpha) antibodies and loss of clinical responsiveness to IFN-alpha treatment, we examined sera from 59 patients with hairy cell leukemia who responded to therapy with recombinant IFN-alpha-2a (rIFN-alpha-2a). During the first 2 years of therapy, 10 patients developed rIFN-alpha- 2a-neutralizing and 15 rIFN-alpha-2a-binding antibodies. Nine of the 59 initially responding patients became resistant to rIFN-alpha-2a and suffered a relapse of the disease at 7 to 24 months of treatment. All nine relapsing patients tested positive for both neutralizing and binding antibodies with titers above 400 INU/mL, while none of the antibody-negative patients relapsed. Six patients with detectable binding antibody titers below 400 INU/mL continued to respond to treatment. By measuring the IFN kinetics and the levels of the IFN- induced Mx-homologous protein in mononuclear cells after a single injection each of rIFN-alpha-2a and nIFN-alpha the IFN antibodies of eight of the nine resistant rIFN-alpha patients were found to be highly specific for rIFN-alpha-2a. Therefore, these eight patients were switched to natural IFN-alpha (nIFN-alpha) therapy at doses of 3 million IU, three times a week. All eight patients responded to treatment with nIFN-alpha, achieving durable objective responses similar to those obtained previously with rIFN-alpha-2a. These data clearly demonstrate that rIFN-alpha antibody-positive patients can effectively be treated with nIFN-alpha.


Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1304-1309 ◽  
Author(s):  
RG Steis ◽  
L Marcon ◽  
J Clark ◽  
W Urba ◽  
DL Longo ◽  
...  

Abstract Activated T cells synthesize and express a cell membrane-bound receptor for interleukin-2 (IL-2) and have recently been shown to secrete a soluble form of the same receptor. Hairy cell leukemia is a chronic disorder caused by expansion of a clonal population of an unusual mononuclear cell of B cell origin. These cells have previously been shown to express an IL-2 receptor on the cell membrane. The sera of 26 patients with hairy cell leukemia were examined for the presence of a soluble IL-2 receptor before and during therapy with either recombinant interferon alpha-2a or 2′-deoxycoformycin. Before therapy, all patients had markedly elevated levels of this soluble IL-2 receptor ranging from five to 60 times the highest level observed in normal control sera. In individual patients changes in the level during therapy correlated well with clinical assessments of tumor response; levels fell to near the normal range in patients responding to therapy. Patients not responding to interferon alpha had no significant change in the soluble IL-2 receptor level. These results suggest that hairy cells secrete a soluble IL-2 receptor and that serial measurements of the level of this receptor in the serum can be used as a noninvasive means to assess disease response to therapy.


1989 ◽  
Vol 7 (10) ◽  
pp. 1533-1538 ◽  
Author(s):  
A D Ho ◽  
J Thaler ◽  
F Mandelli ◽  
F Lauria ◽  
R Zittoun ◽  
...  

Interferon-alpha (IFN-a) or 2'-deoxycoformycin (pentostatin; DCF) have each been shown to be highly active in hairy-cell leukemia (HCL). In this phase II study of the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC), the efficacy and toxicity of DCF were investigated in patients who were resistant to IFN-a treatment. Resistance was defined as: (1) progressive disease (PD) under IFN-a therapy for more than 2 months; (2) stable disease (SD) after more than 6 months of IFN-a treatment; (3) relapse within 3 months of discontinuing IFN-a; and (4) intolerance to IFN-a because of World Health Organization (WHO) grade 3 or 4 toxicity. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Responders were given a maintenance therapy once per month for a maximum of 6 months. At the time of report, 33 patients with resistant disease were evaluable for response and toxicity. Median duration of IFN-a therapy before DCF administration was 14.7 months (range, 1 to 41 months). Complete remissions (CRs) were achieved in 11 patients and partial remissions (PRs) in 15, resulting in a total response rate of 78.8%. Median interval between beginning of DCF therapy to best response was 3.9 months with a range from 2.0 to 7.0 months. Two patients who achieved PR have relapsed 7 and 14 months after cessation of DCF therapy. The median duration of response was over 11.5 months (range, over 3.0 to over 24.0 months). Three patients died within the first 6 weeks of DCF treatment: one of drug-unrelated cardiomyopathy and two of fungal pneumonia. The patients with early death (n = 3) and nonresponsive disease (n = 4) received IFN-a treatment for a longer period (median, 18.0 months) than did the 26 responsive patients (median, 10.0 months). Major side effects included nausea, skin rash, and infections and were otherwise mild. Thus, DCF is highly active in patients with HCL resistant to IFN-a.


Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 967-970 ◽  
Author(s):  
P Lehn ◽  
F Sigaux ◽  
D Grausz ◽  
P Loiseau ◽  
S Castaigne ◽  
...  

Abstract Low-dose interferon-alpha (IFN-alpha) therapy is consistently effective in the treatment of hairy cell leukemia (HCL). In two cases of resistance to IFN-alpha administration, we diagnosed variant HCL, a form of HCL with intermediate features between typical HCL and B cell prolymphocytic leukemia. We tried to distinguish variant and typical hairy cells (HCs) by Northern blot analysis of the oncogenes expressed in vivo. We report that variant HCs contain c-myc transcripts in contrast to typical HCs, whereas c-fos transcripts are detected in both cell types. We also report that the mRNA levels of c-myc are not modified in variant HCs by IFN-alpha treatment, whereas the level of c- fos mRNA is modulated in both types of HCs. Our findings suggest that the failure to modulate c-myc expression in vivo might indicate the limits of low-dose IFN-alpha therapy.


Blood ◽  
1994 ◽  
Vol 83 (10) ◽  
pp. 2931-2938 ◽  
Author(s):  
P Kampmeier ◽  
R Spielberger ◽  
J Dickstein ◽  
R Mick ◽  
H Golomb ◽  
...  

Abstract We report that there is an unexpectedly high incidence of second neoplasms in patients after treatment of hairy cell leukemia (HCL) with interferon alpha 2b (IFN). In a cohort of 69 patients with HCL entered in a protocol using IFN as the primary treatment, and followed thereafter for a median of 91 months (range, 0.2 to 109 months), 13 patients (19%) developed a second neoplasm. Six neoplasms were of hematopoietic origin, whereas the remaining seven were adenocarcinomas. The expected number of second tumors in this cohort is three (based on calculations from the National Cancer Institute's SEER data), so the excess frequency (observed:expected) is 4.33. However, the excess frequency is even greater for the hematopoietic neoplasms; the expected frequency is 0.15, whereas six hematopoietic tumors occurred, for an observed:expected ratio of 40. In general, the second neoplasms have behaved aggressively, and the median survival after diagnosis of the second neoplasm was only 8.8 months. Although we cannot entirely exclude the possibility that IFN therapy has some direct oncogenic effect, we suspect that increased frequency of second tumors is related to prolonged survival of patients who are immunocompromised because of HCL and thus prone to develop second tumors. If so, the frequency of second neoplasms in patients with HCL may be even greater in the future with continued improvements in therapy.


1987 ◽  
Vol 65 (20) ◽  
pp. 975-979 ◽  
Author(s):  
A. D. Ho ◽  
R. Kuse ◽  
O. Prümmer ◽  
F. Porzsolt ◽  
W. Hunstein

Cancer ◽  
1988 ◽  
Vol 61 (2) ◽  
pp. 288-293 ◽  
Author(s):  
F. Porzsolt ◽  
W. Digel ◽  
H. Jacobsen ◽  
S. Mittnacht ◽  
H. Kirchner ◽  
...  

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