Incidence of Pneumocystis jirovecii pneumonia after temozolomide for ...

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temozolomide summary points. ○ There is no consensus on use of Pneumocystis jirovecii pneumonia (PJP) prophylaxis for patients receiving temozolomide ...

CNS Oncology

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Incidence of Pneumocystis jirovecii pneumonia after temozolomide for CNS malignancies without prophylaxis Alexander J Neuwelt‡,1, Tam M Nguyen‡,2, Rongwei Fu3,4, Joseph Bubalo5, Rose Marie Tyson2, Cynthia Lacy2, Seymur Gahramanov6, Morad Nasseri2, Penelope D Barnes7 & Edward A Neuwelt*,2,8,9 Summary points ●● There is no consensus on use of Pneumocystis jirovecii pneumonia (PJP) prophylaxis for patients

receiving temozolomide, nor duration of temozolomide, for glioblastoma multiforme (GBM) or highgrade glioma patients. ●● Evidence for PJP during chemoradiotherapy (CRT) is very limited. However, adverse events was associated with the use of PJP prophylaxis during CRT, for example, Green et al. reported a 15.2% of adverse reactions and 3.1% of severe adverse reactions (mainly leukopenia) in non-HIV adults. ●● This group of brain tumor patients were treated with temozolomide without prophylaxis since 1999, and temozolomide was given until progression. ●● A single case of PJP occurred among 240 consecutive patients with GBM and other brain tumors treated at a single institution (0.4%). The proportion was one in 127 (0.8%) among patients receiving concurrent CRT. ●● The patient that developed PJP also had herpes zoster and aspergillus suggestive of underlying immunodeficiency. ●● The rate of PJP is low even if the patients had multiple risk factors in addition to the use of temozolomide. ●● For patients receiving temozolomide until tumor progression, 10% had over 30 courses and no significant toxicity was observed among all patients. ●● A recent meta-analysis by Green et al. suggests PJP prophylaxis should be used only when risk of PJP greater than 3.5%.

Summary Aims: Prophylaxis against Pneumocystis jiroveci pneumonia (PJP) is currently recommended for patients receiving chemoradiation with temozolomide for newly diagnosed glioblastoma multiforme. At our institution, PJP prophylaxis during temozolomide treatment has not been routinely given because of the paucity of supporting data. We investigated the rate of PJP infections in our patients. Patients & methods: We conducted a retrospective

Keywords 

• brain radiation • glioblastoma • Pneumocystis jirovecii • temozolomide

Department of Internal Medicine, University of New Mexico, 1 University of NM, Albuquerque, New Mexico 87131, USA Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA 3 Department of Public Health & Preventative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA 4 Department of Emergency Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA 5 Department of Pharmacy, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA 6 Department of Neurosurgery, University of New Mexico, 1 University of NM, Albuquerque, New Mexico 87131, USA 7 Department of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA 8 Department of Neurosurgery, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA 9 Department of Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA *Author for correspondence: Tel.: +1 503 494 5626; Fax: +1 503 494 5627; [email protected] ‡ Authors contributed equally 1 2

10.2217/CNS.14.24 © 2014 Future Medicine Ltd

CNS Oncol. (2014) 3(4), 267–273

part of

ISSN 2045-0907

267

Research Article  Neuwelt, Nguyen, Fu et al. chart review of 240 brain tumor patients treated between 1999 and 2012 with temozolomide and no PJP prophylaxis, 127 of which received concurrent chemoradiation. Results: One in 240 patients (0.4%; 95% CI: 0.01–2.00; median total dose: 7375 mg/m2; interquartile range: 1300) were diagnosed with PJP. Conclusion: There was a 30 courses

7 (1–54) 7375 (1300) 25 (10)

Comorbid conditions Smoker Diabetes HIV Bone marrow transplant Dialysis Solid organ transplant High steroid exposure History of lymphoma Other hematologic malignancy/dysplasia Severe malnutrition Primary immunodeficiency Nadir median lymphocytes (IQR)# Nadir median WBC (IQR)#

14 (6) 63 (26) 0 0 0 0 213 (89) 2 (0.8)§ 3 (1.2)¶ 1 (0.4) 1 (0.4) 0.7 × 109/l (0.6) 4 × 109/l (2.9)

The percentages do not add up to 100 because some patients had more than one pathology diagnosed on biopsy. 5 procarbazine, lomustine, and vincristine, 10 procarbazine, 1 sunitinib, 19 etoposide, 5 lomustine, 6 methotrexate, 2 rituximab, 3 carmustine, 7 lomustine and 1 ibritumomab tiuxetan. § 1 Non-Hodgkin’s lymphoma and 1 large B-cell lymphoma. ¶ 1 acute myeloid leukemia, 1 chronic lymphocytic leukemia and 1 myelodysplasia. # WBCs were available for 96% (230/240) of patients, and total lymphocyte counts for 81% (195/240) patients. IQR: Interquartile range; WBC: White blood count. † ‡

Discussion The important finding of this study was

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