High incidence of Pneumocystis jirovecii pneumonia in allogeneic hematopoietic cell transplant recipients in the modern era.

Abstract

BACKGROUND:

International guidelines for Pneumocystis jirovecii pneumonia (PJP) prevention recommend prophylaxis for ≥6 months following allogeneic hematopoietic cell transplantation, and longer in patients with graft-versus-host disease (GVHD) or on immunosuppressive therapy (IST). These recommendations are based on cohorts of patients who did not routinely receive anti-thymocyte globulin (ATG) for GVHD prophylaxis.

METHODS:

We performed a retrospective chart review of 649 patients, all of whom received ATG as part of GVHD prophylaxis.

RESULTS:

The cumulative incidence of definite PJP was 3.52% at both 3 and 5 years (median follow up, 1648 days for survivors). PJP occurred in 13 non-GVHD patients between days 207 and 508, due in part to low CD4 T-cell counts (<200 CD4 T cells/µL). PJP occurred in eight GVHD patients between days 389 and 792, due in part to non-adherence to PJP prophylaxis guidelines (discontinuation of PJP prophylaxis at <3 months after discontinuation of IST). Breakthrough PJP infection was not observed in patients receiving prophylaxis with cotrimoxazole, dapsone or atovaquone, whereas three cases were observed with inhaled pentamidine.

DISCUSSION:

In conclusion, for non-GVHD patients receiving ATG-containing GVHD prophylaxis, 6 months of PJP prophylaxis is inadequate, particularly if the CD4 T-cell count is <200 cells/µL or if there is a high incidence of PJP in the community. For patients with GVHD receiving ATG-containing GVHD prophylaxis, continuing PJP prophylaxis until ≥3 months post-discontinuation of IST is important. Cotrimoxazole, dapsone and atovaquone are preferred over inhaled pentamidine.

• Authors: Christopher Evernden, Michelle Dowhan, Rosy Dabas, Ahsan Chaudhry, Amit Kalra, Poonam Dharmani-Khan, Daniel Gregson, Andrew Johnson, Jennifer Jupp, Victor Jimenez-Zepeda, Kareem Jamani, Peter Duggan, Jason Tay, Faisal Khan, Andrew Daly, Jan Storek
• Journal: Cytotherapy (Cytotherapy) Vol. 22 Issue 1 Pg. 27-34 (01 2020) ISSN: 1477-2566 [Electronic] England
• PMID: 31889628 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Antilymphocyte Serum
• Pentamidine
• Trimethoprim, Sulfamethoxazole Drug Combination
• Dapsone
• Atovaquone

Topics

• Adolescent
• Adult
• Aged
• Anti-Bacterial Agents (therapeutic use)
• Antilymphocyte Serum (adverse effects, therapeutic use)
• Atovaquone (therapeutic use)
• CD4 Lymphocyte Count
• Dapsone (therapeutic use)
• Female
• Graft vs Host Disease (drug therapy)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Immunocompromised Host (immunology)
• Immunosuppression Therapy (adverse effects)
• Incidence
• Lymphopenia (chemically induced, immunology)
• Male
• Middle Aged
• Pentamidine (adverse effects, therapeutic use)
• Pneumocystis carinii (isolation & purification)
• Pneumonia, Pneumocystis (drug therapy, epidemiology, prevention & control)
• Retrospective Studies
• Trimethoprim, Sulfamethoxazole Drug Combination (therapeutic use)
• Young Adult