CRITICAL CARE OF THE HEMATOPOIETIC STEM CELL PATIENT
2001; Elsevier BV; Volume: 17; Issue: 3 Linguagem: Inglês
10.1016/s0749-0704(05)70203-7
ISSN1557-8232
AutoresDavid Hořák, Stephen J. Forman,
Tópico(s)Sepsis Diagnosis and Treatment
ResumoAlthough the beginnings of bone marrow transplantation (BMT) date back to 1939 with a case report of intravenous infusion of 18 cm3 of bone marrow from a sibling into a patient with aplastic anemia, 4 Armitage J.O. Bone marrow transplantation. N Engl J Med. 1994; 330: 827-838 Crossref PubMed Scopus (636) Google Scholar , 12 Camp M.J. Wingard J.R. Gilmore C.E. et al. Efficacy of low-dose dopamine in preventing amphotericin B nephrotoxicity in bone marrow transplant patients and leukemic patients. Antimicrob Agents Chemother. 1998; 42: 3103-3106 PubMed Google Scholar modern BMT was pioneered by the Nobel Prize winner E. Donnell Thomas and his fellow investigators who performed the first successful allogeneic BMTs in the late 1960s and early 1970s. Since the last review of critical care complications of BMT in the January, 1988, issue of Critical Care Clinics by Joel Brochstein, MD, 10 Brochstein J.A. Critical care issues in bone marrow transplantation. Crit Care Clin. 1988; 4: 147-166 PubMed Scopus (6) Google Scholar significant strides have been made in basic research and clinical trials, with exponential growth in the numbers of BMTs performed in the 1980s and 1990s. 39 Horowitz M.M. Uses and growth of hematopoietic cell transplantation. in: Thomas E.D. Blume K.G. Forman S.J. Hematopoietic Cell Transplantation. Blackwell Science, Malden, Massachusetts1999: 12-18 Google Scholar Bone marrow is no longer the sole source of allogeneic and autologous hematopoietic cells; peripheral blood stem cell collections and umbilical cord blood are used increasingly, so the preferred term used in the literature is hematopoietic stem cell transplantation (HCT). Worldwide, an estimated 40, 000 transplantations are performed annually. The list of potential disease states amemable to HCT, displayed in the box, continues to expand. 39 Horowitz M.M. Uses and growth of hematopoietic cell transplantation. in: Thomas E.D. Blume K.G. Forman S.J. Hematopoietic Cell Transplantation. Blackwell Science, Malden, Massachusetts1999: 12-18 Google Scholar Diseases in Which Autologous or Allogeneic Hematopoietic Stem Cell Transplants Can Be Used Tabled 1 Malignancies Nonmalignant Diseases Leukemia/preleukemia Severe aplastic anemia Chronic myeloid leukemia Paroxysmal nocturnal hemoglobinuria Acute myeloid leukemia Acute lymphoblastic leukemia Hemoglobinopathies Juvenile chronic myeloid leukemia Thalassemia major Sickle cell disease Myelodysplastic syndromes Congenital disorders of hematopoiesis Therapy-related myelodysplasia/leukemia Fanconi's anemia Chronic lymphocytic leukemia Diamond-Blackfan syndrome Non-Hodgkin's and Hodgkin's lymphoma Kostmann's agranulocytosis Familial erythrophagocytic histiocytosis Multiple myeloma Solid tumors Dyskeratosis congenita Breast cancer Shwachman-Diamond syndrome Testicular cancer Severe combined immunodeficiency and related disorders Ovarian cancer Small cell lung cancer Wiskott-Aldrich syndrome Neuroblastoma Inborn errors of metabolism Open table in a new tab As the number of HCT patients has increased, so has the need for intensive care of the life-threatening complications associated with this high-risk procedure. The ICU use rates in HCT are estimated to range from 7% to 40%, depending on the type of transplant and risk factors such as age, conditioning regimen, and underlying disease. 20 Crawford S.W. Critical care and respiratory failure. in: Thomas E.D. Blume K.G. Forman S.J. Hematopoietic Cell Transplantation. Blackwell Science, Malden, Massachusetts1999: 712-722 Google Scholar At the City of Hope National Medical Center (COHNMC), HCT patients with critical care complications are transferred to a 12-bed combined medical/surgical ICU, whereas at other institutions critically ill patients are managed on the transplantation ward. 74 Parkman R. Bone marrow transplantation and intensive care units: A need for integration. Journal of Intensive Care Medicine. 1987; 2: 297-298 Crossref Scopus (1) Google Scholar The COHNMC uses a multidisciplinary team approach to management of the critically ill HCT patient, with team leadership provided by the primary hematologist/oncologist and the adult or pediatric pulmonary intensivist and with input from a variety of other medical and surgical subspecialists as appropriate, including gastroenterologists, nephrologists, infectious diseases specialists, transfusion medicine specialists, psychiatrists, general surgeons, thoracic surgeons, neurosurgeons, and otolaryngologists. Bedside rounds are made daily in the ICU with input by physicians and nursing, respiratory therapy, dietary, pharmacy, social services, pastoral care, and physical therapy personnel. Several studies have suggested that transitioning from an open to a closed ICU with stricter administrative and triage control by an intensivist leads to more efficient use, shorter length of stay, decreased number of days of mechanical ventilation, lower costs, and improved outcome. 29 Giles K. Vaughan W.E. A model of care for bone marrow transplantation patients: Update 1998. Oncology Issues. 1999; : 21-25 Google Scholar , 63 Manthous C.A. Amoateng-Adjepong Y. Al-Kharrat T. et al. Effects of a medical intensivist on patient care in a community teaching hospital. Mayo Clin Proc. 1997; 72: 391-399 Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar , 70 Multz A.S. Chalfin D.B. Samson I.M. A “closed” medical intensive care unit (MICU) improves resource utilization when compared with an “open” MICU. Am J Respir Crit Care Med. 1998; 157: 1468-1473 Crossref PubMed Scopus (204) Google Scholar At COHNMC and at many cancer centers, however, the team approach has proved to be most effective in the complex management of critically ill HCT patients. Many critical care complications in HCT patients are the same as those that occur in other immunocompromised patients, including sepsis, systemic inflammatory response syndrome (SIRS), multiorgan dysfunction syndrome (MODS), opportunistic infection, drug toxicity, hemorrhage, and so forth. This article focuses on the critical care problems occurring more specifically in the HCT patient, including infection, specific-organ toxicities, graft-versus-host disease (GvHD), and regimen-related toxicity (RRT). Previous reviewers have pointed out that complications following HCT tend to follow a fairly predictable timetable related to the evolution of immunologic changes attributable to the chemoradiation conditioning regimen, with an interval of pancytopenia preceding engraftment. 15 Chan C.K. Hyland R.H. Hutcheon M.A. Pulmonary complications following bone marrow transplantation. Clin Chest Med. 1990; 11: 323-332 PubMed Google Scholar , 20 Crawford S.W. Critical care and respiratory failure. in: Thomas E.D. Blume K.G. Forman S.J. Hematopoietic Cell Transplantation. Blackwell Science, Malden, Massachusetts1999: 712-722 Google Scholar , 50 Krowka M.J. Rosenow E.C. Hoagland H.C. Pulmonary complications of bone marrow transplantation. Chest. 1985; 87: 237-246 Crossref PubMed Scopus (268) Google Scholar , 99 Shanholtz C. Respiratory complications of blood and marrow transplantation. Clinical Pulmonary Medicine. 1999; 6: 254-262 Crossref Scopus (2) Google Scholar , 107 Soubani A.O. Miller K.B. Hassoun P.M. Pulmonary complications of bone marrow transplantation. Chest. 1996; 109: 1066-1077 Crossref PubMed Scopus (300) Google Scholar This timetable, as shown in the box, is sometimes useful in narrowing the differential diagnosis, especially in pulmonary complications occurring after HCT. 109a Stanholz C. Respiratory complications of blood and marrow transplantation. Clin Pulm Med. 1999; 6: 255 Google Scholar Traditionally, complications are grouped as early (occurring within 100 days after HCT) or late (occurring more than 100 days after HCT). Most early complications are related to the chemoradiation myeloablative therapy (regimen-related toxicity, or RRT) and to bacterial, fungal, and herpes simplex virus (HSV) infections. Once engraftment occurs and the white blood cell count starts to rise (approximately day 15 to 20 after HCT, the middle period), the incidence of bacterial infection begins to decrease and the risk for Aspergillus (with a second peak occurring between days 60 and 80 after HCT), and Cytomegalovirus (CMV) interstitial pneumonitis increases. Because of significant overlap of complications occurring in the early, middle and late periods, more specific diagnostic testing almost always is required to determine specific diagnosis and appropriate therapy. Technologic advancements during the past decade in imaging, hemodynamic assessment, and more sensitive culture techniques have facilitated the diagnosis of pulmonary complications, although the precise cause of many complications often remains obscure, and treatment is often empiric and supportive. Time Frame of Pulmonary Complications after Blood and Marrow Transplantation Tabled 1 Early(>30 days) Infectious Middle(30 to 100 days) Interstitial pneumonitis Late(>100 days) Infectious Bacterial Cytomegalovirus Bacteria Fungal (Candida, Aspergillus) Human herpes virus 6 Filamentous fungi (Aspergillus and others) Viruses (non-Cytomegalovirus) Idiopathic pneumonia syndrome Nocardia Aspiration Viruses Mycobacteria Pneumocystis carinii pneumonia Pulmonary edema Infectious GvHD-associated phenomena Cardiac dysfunction Pneumocystis carinii pneumonia Obstructive airways disease Hypervolemia Atypical bacteria Bronchiolitis obliterans Capillary leak Aspergillus Veno-occlusive disease Idiopathic pneumonia syndrome Idiopathic pneumonia syndrome Relapsed disease Diffuse alveolar hemorrhage Diffuse alveolar hemorrhage GvHD = graft-versus-host disease Open table in a new tab Although the beginnings of bone marrow transplantation (BMT) date back to 1939 with a case report of intravenous infusion of 18 cm3 of bone marrow from a sibling into a patient with aplastic anemia, 4 Armitage J.O. Bone marrow transplantation. N Engl J Med. 1994; 330: 827-838 Crossref PubMed Scopus (636) Google Scholar , 12 Camp M.J. Wingard J.R. Gilmore C.E. et al. Efficacy of low-dose dopamine in preventing amphotericin B nephrotoxicity in bone marrow transplant patients and leukemic patients. Antimicrob Agents Chemother. 1998; 42: 3103-3106 PubMed Google Scholar modern BMT was pioneered by the Nobel Prize winner E. Donnell Thomas and his fellow investigators who performed the first successful allogeneic BMTs in the late 1960s and early 1970s. Since the last review of critical care complications of BMT in the January, 1988, issue of Critical Care Clinics by Joel Brochstein, MD, 10 Brochstein J.A. Critical care issues in bone marrow transplantation. Crit Care Clin. 1988; 4: 147-166 PubMed Scopus (6) Google Scholar significant strides have been made in basic research and clinical trials, with exponential growth in the numbers of BMTs performed in the 1980s and 1990s. 39 Horowitz M.M. Uses and growth of hematopoietic cell transplantation. in: Thomas E.D. Blume K.G. Forman S.J. Hematopoietic Cell Transplantation. Blackwell Science, Malden, Massachusetts1999: 12-18 Google Scholar Bone marrow is no longer the sole source of allogeneic and autologous hematopoietic cells; peripheral blood stem cell collections and umbilical cord blood are used increasingly, so the preferred term used in the literature is hematopoietic stem cell transplantation (HCT). Worldwide, an estimated 40, 000 transplantations are performed annually. The list of potential disease states amemable to HCT, displayed in the box, continues to expand. 39 Horowitz M.M. Uses and growth of hematopoietic cell transplantation. in: Thomas E.D. Blume K.G. Forman S.J. Hematopoietic Cell Transplantation. Blackwell Science, Malden, Massachusetts1999: 12-18 Google Scholar Diseases in Which Autologous or Allogeneic Hematopoietic Stem Cell Transplants Can Be Used Tabled 1 Malignancies Nonmalignant Diseases Leukemia/preleukemia Severe aplastic anemia Chronic myeloid leukemia Paroxysmal nocturnal hemoglobinuria Acute myeloid leukemia Acute lymphoblastic leukemia Hemoglobinopathies Juvenile chronic myeloid leukemia Thalassemia major Sickle cell disease Myelodysplastic syndromes Congenital disorders of hematopoiesis Therapy-related myelodysplasia/leukemia Fanconi's anemia Chronic lymphocytic leukemia Diamond-Blackfan syndrome Non-Hodgkin's and Hodgkin's lymphoma Kostmann's agranulocytosis Familial erythrophagocytic histiocytosis Multiple myeloma Solid tumors Dyskeratosis congenita Breast cancer Shwachman-Diamond syndrome Testicular cancer Severe combined immunodeficiency and related disorders Ovarian cancer Small cell lung cancer Wiskott-Aldrich syndrome Neuroblastoma Inborn errors of metabolism Open table in a new tab Diseases in Which Autologous or Allogeneic Hematopoietic Stem Cell Transplants Can Be Used Tabled 1 Malignancies Nonmalignant Diseases Leukemia/preleukemia Severe aplastic anemia Chronic myeloid leukemia Paroxysmal nocturnal hemoglobinuria Acute myeloid leukemia Acute lymphoblastic leukemia Hemoglobinopathies Juvenile chronic myeloid leukemia Thalassemia major Sickle cell disease Myelodysplastic syndromes Congenital disorders of hematopoiesis Therapy-related myelodysplasia/leukemia Fanconi's anemia Chronic lymphocytic leukemia Diamond-Blackfan syndrome Non-Hodgkin's and Hodgkin's lymphoma Kostmann's agranulocytosis Familial erythrophagocytic histiocytosis Multiple myeloma Solid tumors Dyskeratosis congenita Breast cancer Shwachman-Diamond syndrome Testicular cancer Severe combined immunodeficiency and related disorders Ovarian cancer Small cell lung cancer Wiskott-Aldrich syndrome Neuroblastoma Inborn errors of metabolism Open table in a new tab Diseases in Which Autologous or Allogeneic Hematopoietic Stem Cell Transplants Can Be Used Tabled 1 Malignancies Nonmalignant Diseases Leukemia/preleukemia Severe aplastic anemia Chronic myeloid leukemia Paroxysmal nocturnal hemoglobinuria Acute myeloid leukemia Acute lymphoblastic leukemia Hemoglobinopathies Juvenile chronic myeloid leukemia Thalassemia major Sickle cell disease Myelodysplastic syndromes Congenital disorders of hematopoiesis Therapy-related myelodysplasia/leukemia Fanconi's anemia Chronic lymphocytic leukemia Diamond-Blackfan syndrome Non-Hodgkin's and Hodgkin's lymphoma Kostmann's agranulocytosis Familial erythrophagocytic histiocytosis Multiple myeloma Solid tumors Dyskeratosis congenita Breast cancer Shwachman-Diamond syndrome Testicular cancer Severe combined immunodeficiency and related disorders Ovarian cancer Small cell lung cancer Wiskott-Aldrich syndrome Neuroblastoma Inborn errors of metabolism Open table in a new tab As the number of HCT patients has increased, so has the need for intensive care of the life-threatening complications associated with this high-risk procedure. The ICU use rates in HCT are estimated to range from 7% to 40%, depending on the type of transplant and risk factors such as age, conditioning regimen, and underlying disease. 20 Crawford S.W. Critical care and respiratory failure. in: Thomas E.D. Blume K.G. Forman S.J. Hematopoietic Cell Transplantation. Blackwell Science, Malden, Massachusetts1999: 712-722 Google Scholar At the City of Hope National Medical Center (COHNMC), HCT patients with critical care complications are transferred to a 12-bed combined medical/surgical ICU, whereas at other institutions critically ill patients are managed on the transplantation ward. 74 Parkman R. Bone marrow transplantation and intensive care units: A need for integration. Journal of Intensive Care Medicine. 1987; 2: 297-298 Crossref Scopus (1) Google Scholar The COHNMC uses a multidisciplinary team approach to management of the critically ill HCT patient, with team leadership provided by the primary hematologist/oncologist and the adult or pediatric pulmonary intensivist and with input from a variety of other medical and surgical subspecialists as appropriate, including gastroenterologists, nephrologists, infectious diseases specialists, transfusion medicine specialists, psychiatrists, general surgeons, thoracic surgeons, neurosurgeons, and otolaryngologists. Bedside rounds are made daily in the ICU with input by physicians and nursing, respiratory therapy, dietary, pharmacy, social services, pastoral care, and physical therapy personnel. Several studies have suggested that transitioning from an open to a closed ICU with stricter administrative and triage control by an intensivist leads to more efficient use, shorter length of stay, decreased number of days of mechanical ventilation, lower costs, and improved outcome. 29 Giles K. Vaughan W.E. A model of care for bone marrow transplantation patients: Update 1998. Oncology Issues. 1999; : 21-25 Google Scholar , 63 Manthous C.A. Amoateng-Adjepong Y. Al-Kharrat T. et al. Effects of a medical intensivist on patient care in a community teaching hospital. Mayo Clin Proc. 1997; 72: 391-399 Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar , 70 Multz A.S. Chalfin D.B. Samson I.M. A “closed” medical intensive care unit (MICU) improves resource utilization when compared with an “open” MICU. Am J Respir Crit Care Med. 1998; 157: 1468-1473 Crossref PubMed Scopus (204) Google Scholar At COHNMC and at many cancer centers, however, the team approach has proved to be most effective in the complex management of critically ill HCT patients. Many critical care complications in HCT patients are the same as those that occur in other immunocompromised patients, including sepsis, systemic inflammatory response syndrome (SIRS), multiorgan dysfunction syndrome (MODS), opportunistic infection, drug toxicity, hemorrhage, and so forth. This article focuses on the critical care problems occurring more specifically in the HCT patient, including infection, specific-organ toxicities, graft-versus-host disease (GvHD), and regimen-related toxicity (RRT). Previous reviewers have pointed out that complications following HCT tend to follow a fairly predictable timetable related to the evolution of immunologic changes attributable to the chemoradiation conditioning regimen, with an interval of pancytopenia preceding engraftment. 15 Chan C.K. Hyland R.H. Hutcheon M.A. Pulmonary complications following bone marrow transplantation. Clin Chest Med. 1990; 11: 323-332 PubMed Google Scholar , 20 Crawford S.W. Critical care and respiratory failure. in: Thomas E.D. Blume K.G. Forman S.J. Hematopoietic Cell Transplantation. Blackwell Science, Malden, Massachusetts1999: 712-722 Google Scholar , 50 Krowka M.J. Rosenow E.C. Hoagland H.C. Pulmonary complications of bone marrow transplantation. Chest. 1985; 87: 237-246 Crossref PubMed Scopus (268) Google Scholar , 99 Shanholtz C. Respiratory complications of blood and marrow transplantation. Clinical Pulmonary Medicine. 1999; 6: 254-262 Crossref Scopus (2) Google Scholar , 107 Soubani A.O. Miller K.B. Hassoun P.M. Pulmonary complications of bone marrow transplantation. Chest. 1996; 109: 1066-1077 Crossref PubMed Scopus (300) Google Scholar This timetable, as shown in the box, is sometimes useful in narrowing the differential diagnosis, especially in pulmonary complications occurring after HCT. 109a Stanholz C. Respiratory complications of blood and marrow transplantation. Clin Pulm Med. 1999; 6: 255 Google Scholar Traditionally, complications are grouped as early (occurring within 100 days after HCT) or late (occurring more than 100 days after HCT). Most early complications are related to the chemoradiation myeloablative therapy (regimen-related toxicity, or RRT) and to bacterial, fungal, and herpes simplex virus (HSV) infections. Once engraftment occurs and the white blood cell count starts to rise (approximately day 15 to 20 after HCT, the middle period), the incidence of bacterial infection begins to decrease and the risk for Aspergillus (with a second peak occurring between days 60 and 80 after HCT), and Cytomegalovirus (CMV) interstitial pneumonitis increases. Because of significant overlap of complications occurring in the early, middle and late periods, more specific diagnostic testing almost always is required to determine specific diagnosis and appropriate therapy. Technologic advancements during the past decade in imaging, hemodynamic assessment, and more sensitive culture techniques have facilitated the diagnosis of pulmonary complications, although the precise cause of many complications often remains obscure, and treatment is often empiric and supportive. Time Frame of Pulmonary Complications after Blood and Marrow Transplantation Tabled 1 Early(>30 days) Infectious Middle(30 to 100 days) Interstitial pneumonitis Late(>100 days) Infectious Bacterial Cytomegalovirus Bacteria Fungal (Candida, Aspergillus) Human herpes virus 6 Filamentous fungi (Aspergillus and others) Viruses (non-Cytomegalovirus) Idiopathic pneumonia syndrome Nocardia Aspiration Viruses Mycobacteria Pneumocystis carinii pneumonia Pulmonary edema Infectious GvHD-associated phenomena Cardiac dysfunction Pneumocystis carinii pneumonia Obstructive airways disease Hypervolemia Atypical bacteria Bronchiolitis obliterans Capillary leak Aspergillus Veno-occlusive disease Idiopathic pneumonia syndrome Idiopathic pneumonia syndrome Relapsed disease Diffuse alveolar hemorrhage Diffuse alveolar hemorrhage GvHD = graft-versus-host disease Open table in a new tab Time Frame of Pulmonary Complications after Blood and Marrow Transplantation Tabled 1 Early(>30 days) Infectious Middle(30 to 100 days) Interstitial pneumonitis Late(>100 days) Infectious Bacterial Cytomegalovirus Bacteria Fungal (Candida, Aspergillus) Human herpes virus 6 Filamentous fungi (Aspergillus and others) Viruses (non-Cytomegalovirus) Idiopathic pneumonia syndrome Nocardia Aspiration Viruses Mycobacteria Pneumocystis carinii pneumonia Pulmonary edema Infectious GvHD-associated phenomena Cardiac dysfunction Pneumocystis carinii pneumonia Obstructive airways disease Hypervolemia Atypical bacteria Bronchiolitis obliterans Capillary leak Aspergillus Veno-occlusive disease Idiopathic pneumonia syndrome Idiopathic pneumonia syndrome Relapsed disease Diffuse alveolar hemorrhage Diffuse alveolar hemorrhage GvHD = graft-versus-host disease Open table in a new tab Time Frame of Pulmonary Complications after Blood and Marrow Transplantation Tabled 1 Early(>30 days) Infectious Middle(30 to 100 days) Interstitial pneumonitis Late(>100 days) Infectious Bacterial Cytomegalovirus Bacteria Fungal (Candida, Aspergillus) Human herpes virus 6 Filamentous fungi (Aspergillus and others) Viruses (non-Cytomegalovirus) Idiopathic pneumonia syndrome Nocardia Aspiration Viruses Mycobacteria Pneumocystis carinii pneumonia Pulmonary edema Infectious GvHD-associated phenomena Cardiac dysfunction Pneumocystis carinii pneumonia Obstructive airways disease Hypervolemia Atypical bacteria Bronchiolitis obliterans Capillary leak Aspergillus Veno-occlusive disease Idiopathic pneumonia syndrome Idiopathic pneumonia syndrome Relapsed disease Diffuse alveolar hemorrhage Diffuse alveolar hemorrhage GvHD = graft-versus-host disease Open table in a new tab
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