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Alert Number 5

Sinus and Pulmonary Problems in CLL

Date: March 22, 2004

Many of you have written and expressed interest in the "Best Practices" article and what you and your oncologist need to know. This Topics Alert is to reiterate a couple of points that are of immense significance to all CLL patients.

As you can see from the very recent and pivotal paper from Dr. Kanti Rai et al, pneumonia and related pulmonary infections were the single biggest reason for hospitalization and death in CLL patients. Which patients were most at risk? Patients with significantly reduced levels of neutrophils, and high blood urea nitrogen (BUN) levels. The second abstract from Dr. Byrd (another well respected CLL expert) goes on to explain the potential risk of fludarabine therapy in precipitating neutropenia and therefore pulmonary infections, especially in patients who have also had corticosteroid therapy (prednisone, methylprednisolone, dexamethasone etc) and alkylating agent therapy (cyclophosphamide). The recommendation is quite explicit and clear: "Aggressive work-up of pulmonary syndromes and PCP prophylaxis in these patients should be considered during and after treatment with fludarabine."

In other words, do NOT neglect sinus or chest problems if you have CLL, and do discuss with your doctor the use of pre-emptive medications to protect you against pulmonary infections prior to use of fludarabine or other immunosuppressive drugs. Once pulmonary infections take root and establish themselves, it is not always easy to get rid of them and they can make the difference between good quality life or otherwise. I just heard from one CLL patient and friend who has been through just about every known chemotherapy regime and looking at a bone marrow transplant as his best remaining choice. The problem is that he has had a long standing sinus infection, (he has had dexamethasone, fludarabine, cyclophosphamide, you name it), and the doctors are very reluctant to proceed with the transplant because of the existing infections. Did you know that the mortality rates for transplants get a lot worse if you go in with a 'live' infection? Seems obvious, once you think about it.

I see far too many "home remedies" for dealing with chronic sinus infections on the Internet chat rooms. Some of these may indeed help, but some may do little more than help you breathe a little easier for a short while. But without a concerted effort to kill the bug causing the infection, you may be only tinkering with the symptoms on a superficial basis. Viruses have a nasty way of hiding dormant for a long time, then getting into an attack mode when your immune system is down and there is a window of opportunity for them. As CLL patients with compromised immune systems, we should be particularly aware of reduced neutrophils and immune function due to therapy, and take preemptive precautions.

You can learn more about chronic inflammation and pulmonary problems in CLL by reading two recent Topics articles Role of Pulmonary Inflammation in CLL and CLL, Chronic Inflammation and What You Can Do About It.

Be well,



Cancer. 2003 Nov 1;98(9):1912-7.

Pulmonary complications in chronic lymphocytic leukemia.

Ahmed S, Siddiqui AK, Rossoff L, Sison CP, Rai KR.

Divisions of Hematology and Oncology, Long Island Jewish Medical Center, New Hyde Park, New York 11040

BACKGROUND: Although pulmonary complications account for significant morbidity and mortality in patients with chronic lymphocytic leukemia (CLL), to the authors' knowledge there are sparse data available in published literature. The authors evaluated pulmonary complications in patients with CLL and identified prognostic variables that predict hospital mortality in these patients.
METHODS: Clinical data were analyzed retrospectively from patients with CLL who required hospitalization for a respiratory illness at a tertiary care institution from January 1993 to December 2001. A logistic regression analysis with a backward elimination procedure was carried out to determine prognostic variables that predict hospital mortality.
RESULTS: There were 110 patients who were admitted on 142 occasions with a pulmonary complication. The median age was 75 years (range, 43-97 years), and the male:female ratio was 1.7:1.0. Among 142 admissions, 68% were high risk according to the Rai criteria, 68% of patients admitted had received prior therapy for CLL, and 35% had received treatment within 3 months of admission. The most common pulmonary complications were pneumonias (75%), malignant pleural effusion/and or lung infiltrate due to CLL (9%), pulmonary leukostasis (4%), Richter transformation or nonsmall cell lung carcinoma (3%), and upper airway obstruction (2%). Forty-four of 110 patients (40%) died. In multivariate analysis, admission absolute neutrophil counts </= levels (BUN) nitrogen urea blood and 1.3-16.6) CI], [95% interval confidence 95% 4.6; ratio, (odds L 10(9) x 0.5>/= 20 mg/dL (odds ratio, 3.0; 95% CI, 1.1-8.3) were correlated significantly with mortality.
CONCLUSIONS: Pneumonia was the major pulmonary complication in hospitalized patients with CLL. Severe neutropenia and high BUN levels were correlated significantly with increased mortality.

Copyright 2003 American Cancer Society.

PMID: 14584074

Am J Hematol. 1995 Jun;49(2):135-42.

Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis.

Byrd JC, Hargis JB, Kester KE, Hospenthal DR, Knutson SW, Diehl LF.

Hematology-Oncology Service, Walter Reed Army Medical Center, Washington, DC 20307

The high incidence of opportunistic pulmonary infections in fludarabine-treated patients at Walter Reed Army Medical Center (WRAMC) and in the literature are described. A CancerLit search of fludarabine from June 1983-April 1994 with subsequent cross referencing and a retrospective review of all patients receiving fludarabine at WRAMC was performed. A total of 2,269 patients with low-grade lymphoid malignancies who received 7,547 + cycles of fludarabine were identified from the literature. Seventy-three (3.2%) of these patients developed opportunistic infections. Seventy-one (97%) of these infections occurred in patients who were pretreated with alkylator regimens or corticosteroids. Forty-five (2%) of these were of respiratory origin and associated with a 56% mortality rate. In contrast, 6 of the 21 patients (29%) treated with fludarabine at WRAMC developed opportunistic pulmonary infections which included three Pneumocystis carinii (PCP), one PCP/disseminated Candidiasis, one Mycobacterium avium intracellulare, and one Aspergillus niger pneumonia. These infections developed during and after treatment with fludarabine in alkylator-resistant patients who had received corticosteroids before (n = 6), during (n = 1), or after (n = 4) fludarabine therapy. Lack of PCP prophylaxis was the only significant (P = .018) variable that differentiated patients who developed opportunistic pulmonary infections. Corticosteroid treatment before, during, or after fludarabine treatment in patients with alkylator-resistant, low-grade lymphoid malignancies who have not received PCP prophylaxis is associated with an increased risk of opportunistic pulmonary infections. Aggressive work-up of pulmonary syndromes and PCP prophylaxis in these patients should be considered during and after treatment with fludarabine.

PMID: 7771465

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