2-chloro-3--deoxyadenosine and Leukemia--Hairy-Cell

Hairy cell leukemia represent 2% of all the leukemias. The etiology is unknown. The diagnosis is based on the peripheral blood examination, showing characteristic lymphoid B cells, with loose lacy chromatin and unconstant cytoplasmic projections. The abnormal lymphoid cells express CD19, CD20, CD22, CD79a, CD25 and CD103. The tumor cells are Sig + with clonal light chain restriction. The treatment is based on recombinant IFN: we discuss the interest and the risks of second malignancy related to the prescription of the purine analogues.

Topics: 2-Chloroadenosine; Antigens, CD; Antimetabolites, Antineoplastic; Antineoplastic Agents; B-Lymphocytes; Bone Marrow; Clinical Trials as Topic; Deoxyadenosines; Humans; Immunologic Factors; Interferon Type I; Leukemia, Hairy Cell; Neoplasm Proteins; Neoplasms, Second Primary; Neoplastic Stem Cells; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Recombinant Proteins; Splenectomy; Vidarabine

Hairy cell leukemia (HCL) is a chronic B-cell malignancy, typically seen in middle-aged men, characterized by pancytopenia, splenomegaly, immunologic abnormalities, and morphologically typical neoplastic mononuclear cells in the blood, bone marrow, liver, spleen, and other tissues. Diagnosis is confirmed by demonstration of hairy cells in biopsy specimens from the bone marrow or spleen or in peripheral blood. The natural history of this lymphoproliferative disorder varies. Patients may die early during the initial phase of therapy; others may require no therapy; and for some, splenectomy alone, without further treatment, may suffice for many years. Recently, the nucleosides pentostatin (2'-deoxycoformycin) (DCF) and 2'-chlorodeoxyadenosine (2-CdA) have been shown to produce greater numbers of durable complete remissions with curative potential in patients with HCL. The treatment options, with emphasis on major therapeutic advances with alpha-interferon, DCF, and 2-CdA, are reviewed in this article.. Studies on HCL published from 1958 to 1992 were reviewed using the Cancerline and Medline retrieval systems and other bibliographies.. Management of HCL has changed in the last decade as a result of three new effective agents: alpha-interferon DCF, and 2-CdA. DCF has produced an overall response rate of 86% and a complete remission rate of 62%. 2-CdA has yielded an overall response rate of 95% and a complete remission rate of 82%. Alpha-interferon has given an overall response rate of 82% and a complete remission rate of 8%. Other agents with limited activities include chlorambucil, cyclophosphamide, cytarabine, vincristine, doxorubicin, and zorubicin hydrochloride. The effects of lithium carbonate, immunotherapy, splenic irradiation, androgens, and leukaphoresis are minimal and transient.. Modern management of HCL with 2-CdA and DCF is now potentially curative rather than palliative in some patients; however, the optimal therapeutic approach remains uncertain. Alpha-interferon has been approved by the Food and Drug Administration as the first-line drug therapy, followed by DCF in non-responding patients. 2-CdA remains an experimental therapy, but its higher response rate and ease of administration may make it the first-line treatment of choice. Additional research into the biology of HCL and further clinical trials are needed to determine the optimal treatment strategy for this disorder. Therefore, the best therapeutic approach at the current time is to include patients with HCL in ongoing clinical trials.

Topics: 2-Chloroadenosine; Deoxyadenosines; Forecasting; Granulocyte Colony-Stimulating Factor; Humans; Interferons; Leukemia, Hairy Cell; Male; Pentostatin; Splenectomy; Vidarabine

Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder. Treatment options available are splenectomy, interferon, DCF and 2-CdA. 2-CdA is considered to have curative potential as proved by the other studies.. We gave 2-CdA in a dose of 0.09/kg/day as a continuous infusion in sixteen patients of hairy cell leukaemia.. Three patients developed neutropenia post transfusion. At the end of three months all patients were in remission. Two patients relapsed at the median follow-up of 15 months.. 2-CdA in HCL can achieve complete remission, prolonged survival and care as well.

Topics: 2-Chloroadenosine; Adult; Antimetabolites, Antineoplastic; Deoxyadenosines; Female; Humans; Leukemia, Hairy Cell; Male; Middle Aged; Neutropenia; Survival Rate; Treatment Outcome

Between January 1991 and January 1994, 40 patients with hairy-cell leukemia (HCL), 30 males and 10 females, with a median age of 54 years, were treated with a single course of 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg/day continuous infusion for 7 days. Thirteen patients were untreated and 27 had previously received alpha-interferon. Thirty out of 40 patients (75%) achieved complete remission (CR) and 10 (25%) partial remission (PR). The median follow-up duration for patients in CR has been 48 months (range 30-66). Five of the complete responders (17%) relapsed at 12, 24, 26, 30 and 36 months after treatment as documented by the increase of hairy cells (Hc) in the bone marrow and two of them, who were retreated with 2-CdA after showing an initial impairment of peripheral blood values, obtained a second CR. The remaining three relapsed patients were never retreated and still show normal peripheral counts after 30, 38 and 40 months. Twelve of the continuous complete responder patients are still in CR after more than 5 years. In contrast, 8 out of 10 partial responders progressed after 8-36 months and all of them were retreated with 2-CdA at a dose of 0.15 mg/kg/day for 5 days i.v. Four of them (50%) achieved a CR, three a better PR and one patient died 6 months after the second 2-CdA course because of infectious complications. Two additional patients, both in CR, died after 28 and 37 months because of a second neoplasm. Toxic side-effects consisted of febrile episodes recorded in 16 patients: in seven of them, fever lasted only 24-48 h after the end of treatment and was apparently not infection-related. In the remaining nine patients, showing in addition severe neutropenia (neutrophils less than 1.0 x 10(9)/l), fever was related to bacterial infection requiring systemic antibiotics in all of them and G-CSF in three cases. In conclusion, 2-CdA induces a very high proportion of complete and long-lasting remissions in patients with HCL. In a number of cases relapse at bone marrow level may not affect peripheral blood values for prolonged time. However, in those patients with initial pancytopenia a retreatment with 2-CdA is still effective in inducing a durable second CR.

Topics: 2-Chloroadenosine; Antimetabolites, Antineoplastic; Bone Marrow; Deoxyadenosines; Disease-Free Survival; Female; Follow-Up Studies; Humans; Leukemia, Hairy Cell; Male; Middle Aged; Neoplasms, Second Primary; Splenomegaly; Survival Rate; Time Factors

Historically, the first treatment choices for hairy cell leukemia (HCL) were splenectomy and alpha-interferon. Recently, purine analogues (pentostatin and cladribine) changed radically the treatment modality, inducing complete and durable responses in the majority of patients.. The authors analyzed the outcome of different lines of therapy in 121 HCL patients followed in their institute from 1986 to 2008, with a median follow-up of 105 months. Patients were divided into subgroups according to the number of treatments; Group A included 121 patients who underwent a front-line therapy, Group B patients (n =53) were treated with 2 lines, Group C patients (n = 34) with 3 lines, Group D patients (n = 17) with 4 lines, and Group E patients (n = 8) with 5 lines.. In Group A, 92 (77%) patients obtained a complete response (CR), 23 (18%) a partial response, and the remaining 6 (5%) a minor or no response; median duration of response was 2.7 years. In Group B, 53 relapsed patients achieved a second CR rate of 73.5%; median duration of response was 2.5 years. Group C contained 34 patients in a second relapse, with a CR rate after the third line of treatment of 70.5% (median duration of response, 2.2 years). In Group D, 11 (64.7%) patients obtained a CR (median duration of response, 1.6 years), and in Group E 4 (50%) of 8 patients achieved a CR (median duration of response, 1.3 years).. This study confirms the high risk (>40% of all patients) of retreatment of HCL patients and the need to maximize primary response.

Topics: 2-Chloroadenosine; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Deoxyadenosines; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Leukemia, Hairy Cell; Male; Middle Aged; Retreatment; Splenectomy; Treatment Outcome

Topics: 2-Chloroadenosine; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Antimetabolites, Antineoplastic; Deoxyadenosines; Female; Humans; Leukemia, Hairy Cell; Treatment Outcome

Hairy cell leukemia variant (HCL-v) is a rare form of a chronic B-cell lymphoproliferative disorder. Unlike typical hairy cell leukemia (HCL) where the complete response (CR) rate to 2-chlorodeoxyadenosine and 2'-deoxycoformycin can approach about 90%, in HCL-v CR is rare and partial response (PR) occurs in approximately 50% with these agents. Rituximab treatment in relapsed or refractory HCL results in a CR of 13% to 53%, but its use in HCL-v has not been reported in the literature to our knowledge. We describe a patient with HCL-v, whose course was previously complicated by pure red cell aplasia who achieved CR after treatment with rituximab. We also briefly review outcomes of treatments used in HCL-v reported in the current literature.

Topics: 2-Chloroadenosine; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Combined Modality Therapy; Cyclophosphamide; Deoxyadenosines; Disease Progression; Drug Resistance, Neoplasm; Fatal Outcome; Humans; Interferon-alpha; Leukemia, Hairy Cell; Male; Neoplasms, Second Primary; Prednisolone; Recurrence; Red-Cell Aplasia, Pure; Remission Induction; Rituximab; Splenectomy; Urinary Bladder Neoplasms

Topics: 2-Chloroadenosine; Aged; Antimetabolites, Antineoplastic; Arm; Deoxyadenosines; Diagnosis, Differential; Diplopia; Facial Paralysis; Female; Humans; Hypesthesia; Leukemia, Hairy Cell; Lymph Nodes; Recurrence; Remission Induction; Stroke; Survivors

Peliosis hepatis is an unusual disorder associated with a variety of diseases and treatments. This is the first report of peliosis hepatis associated with administration of 2-chloro-3'-deoxyadenosine. The literature is reviewed.

Topics: 2-Chloroadenosine; Aged; Antineoplastic Agents; Deoxyadenosines; Female; Humans; Leukemia, Hairy Cell; Peliosis Hepatis

Hairy cell leukemia (HCL) is a well recognized indolent B-cell lymphoproliferative disorder. HCL cell proliferation is regulated by growth factors and cytokines, of which tumor necrosis factor-alpha (TNF-alpha) may be one of the most important. The mechanism of TNF-alpha-induced HCL cell growth is mediated via 2 receptors, which are present in both cellular and soluble forms. In this study we determined the serum levels of TNF-alpha and their soluble receptors - sTNF-R60 and sTNF-R80 - in 23 HCL patients and correlated them with clinical parameters before and after therapy. Patients were classified according to their clinical status as either "active" at diagnosis or during relapse and "non-active" (responding to therapy with partial and complete remission). Most patients were treated with 2-CDA, following which serum levels of TNF-alpha, sTNF-R60 and sTNF-R80 were significantly decreased, particularly in CR. Significant differences in paired observation values were noted for TNF-alpha and sTNF-R80, indicating a good correlation with the clinical status of disease, but this was not the case for sTNF-R60 (coefficients of correlation between levels of TNF-alpha and sTNF-R80 and of TNF-alpha and sTNF-R60 were r = 0.85 and r= 0.64, respectively). These results suggest that decreases in both TNF-alpha and sTNF-R80 are indicative of response to treatment, while increased levels accompany active disease. Accordingly, we conclude that serum levels of the TNF family, as for the sIL-2R and IL-1 family, may also be used as sensitive markers for monitoring HCL status. Levels may be indicative of the clinical efficacy of therapy and can be used as an indicator of the presence of residual disease.

Topics: 2-Chloroadenosine; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Deoxyadenosines; Humans; Leukemia, Hairy Cell; Neoplasm, Residual; Prognosis; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha

Red cell distribution width (RDW) was examined in 18 patients with hairy cell leukemia (HCL) treated with 2-chlorodeoxyadenosine (2-CdA), in 5 patients treated with Interferon alpha (IFN-alpha) and in 9 patients subjected to splenectomy. Out of 18 patients treated with 2-CdA one patient was excluded of the study because of association of HCL with acquired sideroblastic anemia. In the remaining 17 patients the mean value of RDW before therapy was 18.8% (range 13.5% to 25.0%) and dropped after successful therapy after 6 to 12 months to the mean value of 13.6% (range 11.2% to 17.9%) and after 18 months to 13.4% (range 12.6% to 14.7%) (p = 0.00015 and p = 0.00049 respectively). The hemoglobin level increased from the mean value of 119 g/l (range 99 g/l to 157 g/l) before therapy to the mean value of 145.9 g/l (range 127 g/l to 172 g/l) after 6 to 12 months and after 18 months to 147.8 g/l (range 132 g/l to 168 g/l) (p = 0.000017 and p = 0.00036 respectively). The same trend was observed in the group of patients treated with IFN-alfa. The RDW decreased from the mean value of 21.3% (range 18.8% to 28.7%) to the mean value of 15.3% (range 12.4% to 16.7%), (p = 0.031). The hemoglobin level increased in this group of patients from the mean value of 115 g/l (range 98 g/l to 127 g/l) to the mean value of 136 g/l (range 127 g/l to 146 g/l) (p = 0.031). In 9 patients in complete hematologic remission 34 to 293 months after splenectomy the mean value of RDW was 13.9% (range 13.0% to 15.5%).. Increased RDW in HCL is associated with active disease and is reversible after successful therapy. This phenomenon has not been reported in the literature yet. Preliminary results show that the increase of RDW may be due to the dyserythropoiesis.

Topics: 2-Chloroadenosine; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Deoxyadenosines; Erythrocyte Indices; Female; Hemoglobins; Humans; Interferon-alpha; Leukemia, Hairy Cell; Male; Middle Aged; Remission Induction; Splenectomy

Hairy cell leukemia (HCL) is a well-recognized chronic lymphoproliferative disorder of B cell lineage, which may be regulated by growth factors including cytokines and cytokine antagonists. Previous studies have shown a good correlation between circulating soluble interleukin-2 receptor (sIL-2R) levels and disease activity and response to therapy was always associated with a decrease in sIL-2R levels. The interleukin-1 (IL-1) family of agonists and antagonists may also be involved in the regulation of hematopoietic malignancies. In the present study, we evaluated members of the IL-1 family (IL-1beta, IL-1 receptor antagonist (IL-1Ra) and IL-1 soluble receptors Type I and Type II (IL-1sRI and IL-1sRII) in 23 patients with HCL. Patients were classified according to the clinical state of their disease. Most were treated with 2-chloro-2'-deoxyadercosine (2-CDA) and treatment was associated with a significant decrease in the serum levels of sIL-2R, IL-1beta and IL-1sRII in patients achieving a complete or partial response. In contrast to the above, levels of IL-1Ra increased during response to treatment and clinical response to 2-CDA was associated with an increase of 122% in IL-1Ra levels, in parallel with a decrease of 63% in IL-1beta and 47% in IL-1sRII levels. These results suggest that the balance between IL-1beta, IL-2 and their soluble receptors or antagonists may be involved in the pathogenesis and immunoregulation of HCL. Serum levels of these cytokines may therefore be used to monitor therapeutic efficacy of therapy in HCL and to detect any residual disease.

Topics: 2-Chloroadenosine; Antimetabolites, Antineoplastic; Deoxyadenosines; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Leukemia, Hairy Cell; Receptors, Interleukin-1; Receptors, Interleukin-1 Type II; Severity of Illness Index; Sialoglycoproteins

Bcl-2 overexpression has been shown to be associated with several malignancies, including B-cell chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas (NHL), mainly low-grade and follicular in type. It has as yet not been described in hairy cell leukemia (HCL). In 30 patients with CLL and 14 with HCL who were consecutively selected for treatment with purine analogues (Fludarabine in CLL and 2-chloro-deoxy-adenosine in HCL), we evaluated bcl-2 oncoprotein expression in leukemic cells on marrow sections that were taken before treatment and stained immunohistochemically with a monoclonal antibody (Dakopatts 124 clone), by the avidin-biotin-peroxidase method. All samples were found to be bcl-2 positive, with a staining intensity that was moderate to strong in CLL and weak to moderate in HCL. 83% of CLL and 100% of HCL patients were responsive to purine analogues. These findings show that bcl-2 is overexpressed in almost all cases CLL and HCL and that bcl-2 overexpression does not predict a poor response to purine analogues, which are believed to induce apoptosis.

Topics: 2-Chloroadenosine; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Biomarkers, Tumor; Deoxyadenosines; Female; Gene Expression Regulation, Neoplastic; Humans; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Proto-Oncogene Proteins c-bcl-2; Vidarabine

2-chlorodeoxyadenosine (2-CDA) is very effective in the treatment of patients with hairy-cell leukaemia, with an overall response rate of 80-95%. The standard treatment is a continuous intravenous infusion for 7 days. The bioavailability of 2-CDA after subcutaneous injection is 100%, but the concentration-time profile is completely different compared to continuous intravenous administration. In the present study we compared the intravenous standard treatment (group 1, n = 22; 0.1 mg/kg/d for 7 days, civ.) with subcutaneous administration of 2-CDA (group 2, n = 62; 0.14 mg/kg/d for 5 days, s.c.) in patients with hairy-cell leukaemia. In group 1, 96% (21/22) of patients responded to 2-CDA (complete remission 73%, partial remission 23%) and in the second group 97% were responsive (complete response 76%, 47/62; partial remission 21%, 13/62). The percentage for moderate and severe infections in the trial with intravenous and subcutaneous treatment was 14% and 26% respectively (p = 0.37). We conclude that subcutaneous administration of 2-CDA in patients with hairy-cell leukaemia is feasible and economical and results in comparable responses and toxicity compared to the intravenous standard treatment.

Topics: 2-Chloroadenosine; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Cohort Studies; Deoxyadenosines; Dose-Response Relationship, Drug; Drug Administration Schedule; Feasibility Studies; Female; Humans; Infusions, Intravenous; Injections, Subcutaneous; Leukemia, Hairy Cell; Male; Middle Aged; Pilot Projects; Prospective Studies; Remission Induction; Treatment Outcome

Topics: 2-Chloroadenosine; Antibodies, Monoclonal; Deoxyadenosines; Humans; Immunoconjugates; Immunotoxins; Leukemia, Hairy Cell; Lymphoma; Pentostatin; Ricin