Letter to the editor: Opportunistic infections in patients with chronic lymphocytic leukemia...
2
American Journal of Hematology 39:314-315 (1992) Letter to the Editor: Opportunistic Infections in Patients With Chronic Lymphocytic Leukemia Following Treatment With Fludarabine Individuals with chronic lymphocytic leukemia (CLL) are immunosuppressed primarily due to hypogamma- globulinemia; infections associated with cell-mediated immune deficiencies are unusual. We report two cases of CLL treated with fludarabine, complicated by Pneumo- cysris carinii pneumonia (PCP) and disseminated Myco- bacterium bovis. Fludarabine, a purine antimetabolite used in CLL, may affect T lymphocytes [ 1,2]. We hy- pothesize that fludarabine creates a deficiency of cell- mediated immunity, predisposing to opportunistic infec- tions. Patient 1 was a 59-year-old man with stage Ill CLL, previously treated with chlorambucil and prednisone; cy- clophosphamide, vincristine, and prednisone (CVP); and doxorubicin. His disease was complicated by autoim- mune hemolytic anemia treated with steroids and sple- nectomy , and by hypogammaglobulinemia treated with immunoglobulin infusions. He received fludarabine 25 mg/m2/day for 5 days monthly for a peripheral blood lymphocytosis, with resulting reduction in his lympho- cyte count. After 8 months, he developed a left lower lobe pneumonia, which persisted despite antibiotics and gammaglobulin infusions. Bronchoscopic washings re- vealed P. carinii. Despite intravenous Septra and penta- midine, the patient died of respiratory failure 6 weeks after the diagnosis of his pneumonia. Patient 2 is a 57-year-old man with stage Ill CLL, previously treated with chlorambucil, prednisone, etopo- side, doxorubicin, and radiation therapy. He also re- ceived immunoglobulin infusion for hypogammaglobu- linemia. Because of progressive lymphadenopathy, he received fludarabine 25 mg/m2/day for 5 days monthly, with resolution of lymphadenopathy and lymphocytosis. After three cycles of fludarabine, he presented with cough and dyspnea. Bronchoscopic washings revealed P. carinii infection, which responded to IV Septra. Two months later, he developed multiple tender, fluctuant, subcutaneous nodules. Biopsy revealed granulomata con- taining acid-fast bacilli; the culture was positive for M. bovis. He was treated with antituberculous medication. Human immunodeficiency virus (HIV) testing was nega- tive. Peripheral blood T4:T8 ratio, determined 8 months later, was normal. Reed et al. [3] reported a case of CLL complicated by coinfection with P. carinii and Cunninghamella berrhol- letiae after treatment with chlorambucil, prednisone, and cyclophosphamide. Dworzack et al. [4] described a case of coinfection with P. carinii and Legionella pneumo- philia after receiving prednisone. Although both our patients had been heavily treated for their CLL before receiving fludarabine, they were not receiving steroids at the time of their opportunistic infec- tions. Furthermore, both patients had been receiving gammaglobulin infusions, and neither patient was neu- tropenic. We considered the possibility that our patients had HIV infection. The first patient was never tested but had no history of high-risk behavior. The second patient had a negative HIV test. Fludarabine may deplete normal T lymphocytes and produce reversal of the T4:T8 ratio [2]. Our patient in whom T4:T8 ratio was normal months after treatment may have had an abnormal ratio during treatment. A case of CLL complicated by PCP and cytomegalo- virus (CMV) infection following fludarabine therapy was recently reported [5], and additional cases of PCP in patients treated with fludarabine have been seen at M.D. Anderson (M. Keating, personal communication). These findings, along with our two cases, suggest that fludara- bine is associated with an increased risk of opportunistic infections. Clinicians using this agent should be aware of this potential toxicity. Catherine Sanders Edith A. Perez H. Jeffrey Lawrence Department of Medicine University of California Davis School of Medicine Davis, California Veterans Affairs Medical Center Martinez, California REFERENCES I. 2. Keating MJ, Kantarjian H, Talpaz M, et al.: Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. Blood 74:19-25, 1989. Boldt DH, Von HoRDD, Kuhn JG, Hersh M: Effects on human periph- eral lymphocytes of in-vivo administration of 9P-D-arabinosyl-2fluoro- adenine-5’-monophosphate (NSC3 12887) Cancer Res 44:466 14666. 1984. 0 1992 Wiley-Liss, Inc.
-
Upload
catherine-sanders -
Category
Documents
-
view
212 -
download
0
Transcript of Letter to the editor: Opportunistic infections in patients with chronic lymphocytic leukemia...
American Journal of Hematology 39:314-315 (1992)
Letter to the Editor: Opportunistic Infections in Patients With Chronic Lymphocytic Leukemia Following Treatment
With Fludarabine Individuals with chronic lymphocytic leukemia (CLL)
are immunosuppressed primarily due to hypogamma- globulinemia; infections associated with cell-mediated immune deficiencies are unusual. We report two cases of CLL treated with fludarabine, complicated by Pneumo- cysris carinii pneumonia (PCP) and disseminated Myco- bacterium bovis. Fludarabine, a purine antimetabolite used in CLL, may affect T lymphocytes [ 1,2]. We hy- pothesize that fludarabine creates a deficiency of cell- mediated immunity, predisposing to opportunistic infec- tions.
Patient 1 was a 59-year-old man with stage Ill CLL, previously treated with chlorambucil and prednisone; cy- clophosphamide, vincristine, and prednisone (CVP); and doxorubicin. His disease was complicated by autoim- mune hemolytic anemia treated with steroids and sple- nectomy , and by hypogammaglobulinemia treated with immunoglobulin infusions. He received fludarabine 25 mg/m2/day for 5 days monthly for a peripheral blood lymphocytosis, with resulting reduction in his lympho- cyte count. After 8 months, he developed a left lower lobe pneumonia, which persisted despite antibiotics and gammaglobulin infusions. Bronchoscopic washings re- vealed P . carinii. Despite intravenous Septra and penta- midine, the patient died of respiratory failure 6 weeks after the diagnosis of his pneumonia.
Patient 2 is a 57-year-old man with stage Ill CLL, previously treated with chlorambucil, prednisone, etopo- side, doxorubicin, and radiation therapy. He also re- ceived immunoglobulin infusion for hypogammaglobu- linemia. Because of progressive lymphadenopathy, he received fludarabine 25 mg/m2/day for 5 days monthly, with resolution of lymphadenopathy and lymphocytosis. After three cycles of fludarabine, he presented with cough and dyspnea. Bronchoscopic washings revealed P. carinii infection, which responded to IV Septra. Two months later, he developed multiple tender, fluctuant, subcutaneous nodules. Biopsy revealed granulomata con- taining acid-fast bacilli; the culture was positive for M . bovis. He was treated with antituberculous medication. Human immunodeficiency virus (HIV) testing was nega- tive. Peripheral blood T4:T8 ratio, determined 8 months later, was normal.
Reed et al. [ 3 ] reported a case of CLL complicated by coinfection with P. carinii and Cunninghamella berrhol-
letiae after treatment with chlorambucil, prednisone, and cyclophosphamide. Dworzack et al. [4] described a case of coinfection with P. carinii and Legionella pneumo- philia after receiving prednisone.
Although both our patients had been heavily treated for their CLL before receiving fludarabine, they were not receiving steroids at the time of their opportunistic infec- tions. Furthermore, both patients had been receiving gammaglobulin infusions, and neither patient was neu- tropenic. We considered the possibility that our patients had HIV infection. The first patient was never tested but had no history of high-risk behavior. The second patient had a negative HIV test.
Fludarabine may deplete normal T lymphocytes and produce reversal of the T4:T8 ratio [2]. Our patient in whom T4:T8 ratio was normal months after treatment may have had an abnormal ratio during treatment.
A case of CLL complicated by PCP and cytomegalo- virus (CMV) infection following fludarabine therapy was recently reported [5], and additional cases of PCP in patients treated with fludarabine have been seen at M.D. Anderson (M. Keating, personal communication). These findings, along with our two cases, suggest that fludara- bine is associated with an increased risk of opportunistic infections. Clinicians using this agent should be aware of this potential toxicity.
Catherine Sanders Edith A. Perez H. Jeffrey Lawrence Department of Medicine University of California Davis School of Medicine Davis, California Veterans Affairs Medical Center Martinez, California
REFERENCES
I .
2.
Keating MJ, Kantarjian H, Talpaz M, et al.: Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. Blood 74:19-25, 1989. Boldt DH, Von HoRDD, Kuhn JG, Hersh M: Effects on human periph- eral lymphocytes of in-vivo administration of 9P-D-arabinosyl-2fluoro- adenine-5’-monophosphate (NSC3 12887) Cancer Res 44:466 14666. 1984.
0 1992 Wiley-Liss, Inc.
Letter to the Editor 315
3 . Reed AE, Body BA, Austin MB, Frierson HF Jr: Cunninghameflu bertholletiue and Pneumocysric carinii pneumonia as a fatal complica- tion of chronic lymphocytic leukemia. Hum Pathol 19: 1470-1472, 1988.
4. Dworzack DL, Ferry JJ, Clark RB: Co-infection with Legionellayneu-
mophila and Pneumocystis carinii in a patient with chronic lymphocytic leukemia. Nebr Med J 74:73-75, 1989.
5. Schilling PJ, Vadhan-Raj S: Concurrent cytomegalovirus and pneumo- cystis pneumonia after fludarabine therapy for chronic lymphocytic leukemia. N Engl J Med 323:833-834, 1990.
