trimethoprim--sulfamethoxazole-drug-combination and Leukemia--Hairy-Cell

Cladribine is a purine analog used in first-line treatment of hairy cell leukemia and in relapsed/refractory chronic lymphocytic anemia. Although cladribine is typically associated with mild, self-limited skin reactions, there is increasing evidence that cladribine may increase the risk of severe cutaneous adverse reactions (SCAR) when combined with drugs classically associated with SCAR (e.g. allopurinol) beyond what would be expected for either drug alone, possibly due to cladribine-induced lymphopenia. We analyzed all SCAR cases reported for cladribine in Janssen's Global Safety Database and found that 26/35 (74.3%) reported concomitant drugs known to be associated with SCAR, most commonly sulfamethoxazole/trimethoprim (SMX/TMP) and allopurinol. In addition, a review of the WHO VigiBase showed that several drugs, including penicillins, SMX/TMP, and allopurinol had a statistically significant contribution to cladribine-associated SCAR. These results lend further support that cladribine may increase the propensity of these drugs to cause SCARs.

Topics: Allopurinol; Cladribine; Humans; Leukemia, Hairy Cell; Skin; Trimethoprim, Sulfamethoxazole Drug Combination

Treatment of hairy cell leukemia (HCL) with cladribine induces durable remissions. Common toxicities are myelosuppression and immunosuppression with low counts of CD4 + T cells. Skin rash (SR) is seldom described. We collected clinical and laboratory data of 35 patients with HCL treated in Hadassah between January 1999 and February 2010, in order to evaluate the frequency and characteristics of SR after treatment with cladribine. We found a high frequency of SR in our group of patients (18/35 patients, 51%), mostly related to febrile neutropenia and concomitant treatment with penicillins/trimethoprim-sulfamethoxazole (TMP-SMZ). The lymphocyte count was low in all patients with SR. We conclude that patients with HCL treated with cladribine have an increased rate of drug hypersensitivity, possibly due to T-cell imbalance induced by cladribine. Since TMP-SMZ and penicillins are related to SR in most cases and are important in the management of patients with HCL, a desensitization protocol should be considered. Rechallenge may be safe after immune reconstitution.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cladribine; Exanthema; Female; Humans; Incidence; Leukemia, Hairy Cell; Male; Middle Aged; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

We present the case of a 74-y-old HIV-negative female who suffered simultaneously from multiple opportunistic infections and a Klebsiella pneumoniae sepsis during high-dose steroids for giant cell arteritis. The patient was treated with a purine analog due to hairy cell leukaemia 10 y previously. Purine analog therapy can lead to long lasting defects in cell-mediated immunity. In these patients, treatment with steroids should be closely monitored with CD4 counts.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Cladribine; Cytomegalovirus; Dexamethasone; Esophagitis; Female; Giant Cell Arteritis; Herpes Simplex; Humans; Klebsiella Infections; Klebsiella pneumoniae; Leukemia, Hairy Cell; Methylprednisolone; Opportunistic Infections; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination

Recombinant interferon-alpha 2 (E. coli) produced a clinically significant improvement in hemoglobin, granulocytes and platelets in 7 of 8 patients with hairy cell leukemia. Response to treatment was already noticeable in the fourth treatment week. In one case without improvement after 120 days, treatment was stopped. So far only one complete remission has been documented. Because of the remarkable improvement in the peripheral blood values, the induction of a complete remission may not be the ultimate goal of interferon treatment. The side effects of this subcutaneous low-dose treatment consisted mainly of mild flu-like symptoms of short duration. The results obtained with recombinant interferon-alpha 2 confirm the initial observation by Quesada et al. with partially purified leukocyte-interferon. In our experience, these results are superior to those obtained in similar conditions with chlorambucil.

Topics: Adult; Aged; Blood Platelets; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Granulocytes; Hemoglobins; Humans; Interferon Type I; Leukemia, Hairy Cell; Male; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination