Weekly administration of 2-chlorodeoxyadenosine in patients with hairy-cell leukemia is effective and reduces infectious complications.

Abstract

BACKGROUND AND OBJECTIVE:

It has been widely demonstrated that one single 7-day course continuous infusion (c.i.) 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily is dramatically effective in inducing high and prolonged complete remission (CR) rates in patients with hairy-cell leukemia (HCL). However, 2-CdA administration often results in severe neutropenia and lymphocytopenia both responsible for the infectious complications observed in these patients. We previously reported preliminary data regarding the effectiveness and toxicity of a modified protocol of 2-CdA administration (0.15 mg/kg 2 hours infusion once a week for 6 courses) in 25 HCL patients. This treatment schedule produced a similar overall response rate compared to standard 2-CdA regimen and appeared to be followed by a lower incidence of infectious episodes. In the present study we report response rate and toxicity of weekly 2CdA administration in a larger cohort of patients and with a longer follow-up.

DESIGN AND METHODS:

In a group of HCL patients with a pronounced decrease in neutrophils count (< 1 x 10(9)/L), we modified the standard protocol (0.1 mg/kg daily x 7 days c.i.) by administering 2-CdA at a dose of 0.15 mg/kg 2 hours infusion once a week for 6 courses. Thirty HCL patients, 24 males and 6 females with a median age of 56 years (range 37-76), entered into this protocol. Seventeen out of 30 patients were at diagnosis while the remaining 13 had been previously treated with alpha-interferon (alpha-IFN) (7), or 2-CdA (4) or deoxycoformycin (DCF) (2).

RESULTS:

Overall, 22/30 (73%) patients achieved CR and 8 (27%) partial remission (PR) with a median duration of response at the time of writing of 35 months, ranging from 6 to 58 months. Five patients (1 CR and 4 PR) have so far progressed. The treatment was very well tolerated. Five out of 30 patients (16%) developed severe neutropenia (neutrophils < 0.5 x 10(9)/L) and only in two of them we did register an infectious complication which required treatment with systemic antibiotics and granulocyte colony-stimulating factor (G-CSF).

INTERPRETATION AND CONCLUSIONS:

In conclusion, we confirm that weekly administration of 2-CdA at a dose of 0.15 mg/kg for 6 courses appears to be very effective in HCL inducing a high CR rate, similar to that observed with daily c.i. administration. CR durability and relapse/progression rates are also comparable to standard 2-CdA schedule. Moreover this new regimen seems to be safer in pancytopenic patients, markedly reducing life-threatening infectious complications.

• Authors: F Lauria, M Bocchia, G Marotta, D Raspadori, P L Zinzani, D Rondelli
• Journal: Haematologica (Haematologica) Vol. 84 Issue 1 Pg. 22-5 (Jan 1999) ISSN: 0390-6078 [Print] Italy
• PMID: 10091389 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Interferon-alpha
• Pentostatin
• Cladribine

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (administration & dosage, therapeutic use)
• Cladribine (administration & dosage, therapeutic use)
• Disease Progression
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Infection Control
• Interferon-alpha (therapeutic use)
• Leukemia, Hairy Cell (complications, drug therapy)
• Lymphopenia (complications)
• Male
• Middle Aged
• Neutropenia (complications)
• Pentostatin (therapeutic use)
• Remission Induction
• Treatment Outcome