Timing and severity of community acquired respiratory virus infections after myeloablative versus non-myeloablative hematopoietic stem cell transplantation

Respiratory virus infections are important causes of morbidity and mortality after hematopoietic cell transplantation. Their clinical course can be severe with progression to lower respiratory tract infection, co-infection with serious pulmonary co-pathogens, and high mortality. The findings of this retrospective cohort study indicate that viral lower respiratory tract infection during the first 100 days after hematopoietic cell transplantation was less common among patients undergoing non-myeloablative conditioning regimens than in those receiving myeloablative conditioning, despite a similar overall rate of acquisition. Background Respiratory virus infections are important causes of morbidity and mortality after hematopoietic cell transplantation. Their clinical course can be severe with progression to lower respiratory tract infection, co-infection with serious pulmonary co-pathogens, and high mortality. Non-myeloablative conditioning regimens achieve engraftment without eradication of host hematopoietic cells, which potentially allows for protection against infections commonly seen in hematopoietic cell transplantation patients treated with standard intensity conditioning regimens. Design and Methods We performed a retrospective cohort study to measure the incidence and severity of parainfluenza types 1–4, influenza (A and B), respiratory syncitial virus and human rhinovirus disease in myeloablative versus non-myeloablative versus autologous hematopoietic cell transplantation patients. Results The incidences of all respiratory virus infections were similar in the non-myeloablative and myeloablative cohorts but less in the autologous cohort (33/420 [7.9%], 150/1593 [9.4%], and 37/751 [4.9%], respectively, p<0.0001). However, respiratory virus lower tract infections were significantly less common during the first 100 days after transplantation in non-myeloablative patients compared to myeloablative and autologous patients (1/420 [0.2%], 34/1593 [2.1%] and 16/751 [2.1%], respectively, p=0.005. Respiratory virus lower tract infection had high co-infection and attributable mortality rates. Conclusions Respiratory virus lower tract infection during the first 100 days after hematopoietic cell transplantation was less common in persons receiving non-myeloablative conditioning regimens compared to myeloablative conditioning, despite a similar overall rate of acquisition.

[1]  M. Maris,et al.  Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. , 2008, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[2]  M. Sorror,et al.  Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed, refractory, and transformed indolent non-Hodgkin's lymphoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  M. Sorror,et al.  Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. , 2008, Blood.

[4]  M. Boeckh,et al.  Rhinovirus as a cause of fatal lower respiratory tract infection in adult stem cell transplantation patients: a report of two cases , 2007, Bone Marrow Transplantation.

[5]  M. Boeckh,et al.  Randomized controlled multicenter trial of aerosolized ribavirin for respiratory syncytial virus upper respiratory tract infection in hematopoietic cell transplant recipients. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  M. Sorror,et al.  Nonmyeloablative unrelated donor hematopoietic cell transplantation to treat patients with poor-risk, relapsed, or refractory multiple myeloma. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[7]  M. Maris,et al.  Unrelated donor status and high donor age independently affect immunologic recovery after nonmyeloablative conditioning. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[8]  M. Boeckh,et al.  Airflow Decline after Myeloablative Allogeneic Hematopoietic Cell Transplantation: The Role of Community Respiratory Viruses , 2006, The Journal of infectious diseases.

[9]  L. Elting,et al.  Parainfluenza virus infection in adult bone marrow transplant recipients , 1993, European Journal of Clinical Microbiology and Infectious Diseases.

[10]  M. Maris,et al.  Immunologic recovery after hematopoietic cell transplantation with nonmyeloablative conditioning. , 2003, Experimental hematology.

[11]  M. Maris,et al.  Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. , 2003, Blood.

[12]  F. Hayden,et al.  Rhinovirus Infections in Hematopoietic Stem Cell Transplant Recipients with Pneumonia , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  M. Maris,et al.  Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study. , 2002, Blood.

[14]  P. Ljungman Respiratory virus infections in stem cell transplant patients: the European experience. , 2001, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[15]  M. Boeckh,et al.  Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell transplantation: the Fred Hutchinson Cancer Research Center experience. , 2001, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[16]  S. Crawford,et al.  Phase 1 evaluation of the respiratory syncytial virus-specific monoclonal antibody palivizumab in recipients of hematopoietic stem cell transplants. , 2001, The Journal of infectious diseases.

[17]  M. Boeckh,et al.  Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome. , 2001, Blood.

[18]  J. Radich,et al.  Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. , 2001, Blood.

[19]  Marrow Transplantation Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients , 2000, Biology of Blood and Marrow Transplantation.

[20]  A. Levitt,et al.  Biological and chemical terrorism: strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup. , 2000, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[21]  J. Koplan Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. , 2000, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[22]  A. Nagler,et al.  Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. , 1998, Blood.

[23]  E. Estey,et al.  Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. , 1997, Blood.

[24]  MD Estella Whimbey,et al.  Community Respiratory Virus Infections in Immunocompromised Patients with Cancer , 1997, The American Journal of Medicine.

[25]  R. Storb,et al.  Phase II study of busulfan, cyclophosphamide and fractionated total body irradiation as a preparatory regimen for allogeneic bone marrow transplantation in patients with advanced myeloid malignancies. , 1995, Bone marrow transplantation.

[26]  H. Deeg,et al.  Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. , 1994, Blood.

[27]  B. Osborne,et al.  An outbreak of respiratory syncytial virus in a bone marrow transplant center. , 1992, The Journal of infectious diseases.

[28]  K. Sullivan,et al.  Effects of treatment regimens on post marrow transplant relapse. , 1991, Seminars in hematology.