Successful treatment of pulmonary aspergillus (ASP) with itraconazole after matched unrelated (MUD) bone marrow transplant (BMT) enriched for graft facilitating cells (GFC)

Sophie Lanzkron, C. Bachier, J. Lowder, C. Berkowitz, C. F. Lemaistre

Research output: Contribution to journalArticle

Abstract

ASP infections are common fungal infections in allogeneic BMT patients (Pts), with mortality as high as 95% in Pts with pulmonary involvement. We report the successful treatment of a Pt who developed pulmonary ASP after receiving a T-cell depleted MUD A 48-yr-old male with a past medical history significant for an autologous stem cell in 1994 for multiple myeloma subsequently developed MDS. He underwent a manipulated MUD BMT in a protocol to enhance GFC in October of 1999. The preparative regimen consisted of thiotepa 5 mg/kg, cyclophosphamide 120 mg/kg, ATG 60 mg/kg, TBI 12 Gy and methylprednisolone 60 mg/kg. The pt received tacrolimus as GVHD prophylaxis. The marrow was treated to deplete erythrocytes, granulocytes, plasma cells, NK cells, Tcells and B lymphocytes (Lym) leaving a population of GFC. The pt received a total of 1.20 × 106/kg CD34+ cells, 0.02 × 106/kg aβ; T cells and 0.08 × l06/kg S T cells. Neutrophil recovery occurred on day + 9 and platelet recovery on day + 19. In late January the patient noted shortness of breath. A chest x-ray demonstrated 2 nodules in the left upper lung field which had been present for 1-4 months. A CT scan of the chest showed nodules in the left and right upper lung fields. Samples from a fine needle aspiration grew ASP flavus. The patient was started on itraconazole (IT) therapy at 200 mg PO BID.In April he had normal immunoglobulin (Ig) levels. Results of RFLP at day +100 showed that the pts. cells were 100% donor. On day +100 he had a WBC count of 11,700 with 9% Lym; 25% CD4+ and 24% were CD8+ the CD4/CD8 ratio was normal at 1.02. One month after beginning IT. a repeat CT scan showed shrinking of all lesions. A prolonged period of immunodefiency is seen in patients who receive MUD BMT. The use of T-cell depleted BMT has had a positive effect on decreasing the incidence of GVHD but has resulted in an increase in graft failure and immunodefiency. Our pt achieved neutrophil engraftment on day +9, had normal Ig levels 5 months post BMT and a normal CD4/CD8 ratio at day+100. To our knowledge this is the first case report of successful treatment of invasive ASP in a pt who underwent a Tcell depleted MUD BMT with itraconazole therapy alone. The early reconstitution of immune function leads us to believe that the method used to manipulate the graft, facilitated engraftment and prevented the development of an overwhelming fungal infection.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART II
StatePublished - 2000
Externally publishedYes

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Transplants
Itraconazole
Aspergillus
Grafts
Bone
T-cells
Bone Marrow
Lung
Computerized tomography
Lymphocytes
Immunoglobulins
T-Lymphocytes
Therapeutics
CD4-CD8 Ratio
Mycoses
Thiotepa
Recovery
Methylprednisolone
Tacrolimus
Platelets

ASJC Scopus subject areas

  • Hematology

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Successful treatment of pulmonary aspergillus (ASP) with itraconazole after matched unrelated (MUD) bone marrow transplant (BMT) enriched for graft facilitating cells (GFC). / Lanzkron, Sophie; Bachier, C.; Lowder, J.; Berkowitz, C.; Lemaistre, C. F.

In: Blood, Vol. 96, No. 11 PART II, 2000.

Research output: Contribution to journalArticle

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title = "Successful treatment of pulmonary aspergillus (ASP) with itraconazole after matched unrelated (MUD) bone marrow transplant (BMT) enriched for graft facilitating cells (GFC)",
abstract = "ASP infections are common fungal infections in allogeneic BMT patients (Pts), with mortality as high as 95{\%} in Pts with pulmonary involvement. We report the successful treatment of a Pt who developed pulmonary ASP after receiving a T-cell depleted MUD A 48-yr-old male with a past medical history significant for an autologous stem cell in 1994 for multiple myeloma subsequently developed MDS. He underwent a manipulated MUD BMT in a protocol to enhance GFC in October of 1999. The preparative regimen consisted of thiotepa 5 mg/kg, cyclophosphamide 120 mg/kg, ATG 60 mg/kg, TBI 12 Gy and methylprednisolone 60 mg/kg. The pt received tacrolimus as GVHD prophylaxis. The marrow was treated to deplete erythrocytes, granulocytes, plasma cells, NK cells, Tcells and B lymphocytes (Lym) leaving a population of GFC. The pt received a total of 1.20 × 106/kg CD34+ cells, 0.02 × 106/kg aβ; T cells and 0.08 × l06/kg S T cells. Neutrophil recovery occurred on day + 9 and platelet recovery on day + 19. In late January the patient noted shortness of breath. A chest x-ray demonstrated 2 nodules in the left upper lung field which had been present for 1-4 months. A CT scan of the chest showed nodules in the left and right upper lung fields. Samples from a fine needle aspiration grew ASP flavus. The patient was started on itraconazole (IT) therapy at 200 mg PO BID.In April he had normal immunoglobulin (Ig) levels. Results of RFLP at day +100 showed that the pts. cells were 100{\%} donor. On day +100 he had a WBC count of 11,700 with 9{\%} Lym; 25{\%} CD4+ and 24{\%} were CD8+ the CD4/CD8 ratio was normal at 1.02. One month after beginning IT. a repeat CT scan showed shrinking of all lesions. A prolonged period of immunodefiency is seen in patients who receive MUD BMT. The use of T-cell depleted BMT has had a positive effect on decreasing the incidence of GVHD but has resulted in an increase in graft failure and immunodefiency. Our pt achieved neutrophil engraftment on day +9, had normal Ig levels 5 months post BMT and a normal CD4/CD8 ratio at day+100. To our knowledge this is the first case report of successful treatment of invasive ASP in a pt who underwent a Tcell depleted MUD BMT with itraconazole therapy alone. The early reconstitution of immune function leads us to believe that the method used to manipulate the graft, facilitated engraftment and prevented the development of an overwhelming fungal infection.",
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T1 - Successful treatment of pulmonary aspergillus (ASP) with itraconazole after matched unrelated (MUD) bone marrow transplant (BMT) enriched for graft facilitating cells (GFC)

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AU - Bachier, C.

AU - Lowder, J.

AU - Berkowitz, C.

AU - Lemaistre, C. F.

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N2 - ASP infections are common fungal infections in allogeneic BMT patients (Pts), with mortality as high as 95% in Pts with pulmonary involvement. We report the successful treatment of a Pt who developed pulmonary ASP after receiving a T-cell depleted MUD A 48-yr-old male with a past medical history significant for an autologous stem cell in 1994 for multiple myeloma subsequently developed MDS. He underwent a manipulated MUD BMT in a protocol to enhance GFC in October of 1999. The preparative regimen consisted of thiotepa 5 mg/kg, cyclophosphamide 120 mg/kg, ATG 60 mg/kg, TBI 12 Gy and methylprednisolone 60 mg/kg. The pt received tacrolimus as GVHD prophylaxis. The marrow was treated to deplete erythrocytes, granulocytes, plasma cells, NK cells, Tcells and B lymphocytes (Lym) leaving a population of GFC. The pt received a total of 1.20 × 106/kg CD34+ cells, 0.02 × 106/kg aβ; T cells and 0.08 × l06/kg S T cells. Neutrophil recovery occurred on day + 9 and platelet recovery on day + 19. In late January the patient noted shortness of breath. A chest x-ray demonstrated 2 nodules in the left upper lung field which had been present for 1-4 months. A CT scan of the chest showed nodules in the left and right upper lung fields. Samples from a fine needle aspiration grew ASP flavus. The patient was started on itraconazole (IT) therapy at 200 mg PO BID.In April he had normal immunoglobulin (Ig) levels. Results of RFLP at day +100 showed that the pts. cells were 100% donor. On day +100 he had a WBC count of 11,700 with 9% Lym; 25% CD4+ and 24% were CD8+ the CD4/CD8 ratio was normal at 1.02. One month after beginning IT. a repeat CT scan showed shrinking of all lesions. A prolonged period of immunodefiency is seen in patients who receive MUD BMT. The use of T-cell depleted BMT has had a positive effect on decreasing the incidence of GVHD but has resulted in an increase in graft failure and immunodefiency. Our pt achieved neutrophil engraftment on day +9, had normal Ig levels 5 months post BMT and a normal CD4/CD8 ratio at day+100. To our knowledge this is the first case report of successful treatment of invasive ASP in a pt who underwent a Tcell depleted MUD BMT with itraconazole therapy alone. The early reconstitution of immune function leads us to believe that the method used to manipulate the graft, facilitated engraftment and prevented the development of an overwhelming fungal infection.

AB - ASP infections are common fungal infections in allogeneic BMT patients (Pts), with mortality as high as 95% in Pts with pulmonary involvement. We report the successful treatment of a Pt who developed pulmonary ASP after receiving a T-cell depleted MUD A 48-yr-old male with a past medical history significant for an autologous stem cell in 1994 for multiple myeloma subsequently developed MDS. He underwent a manipulated MUD BMT in a protocol to enhance GFC in October of 1999. The preparative regimen consisted of thiotepa 5 mg/kg, cyclophosphamide 120 mg/kg, ATG 60 mg/kg, TBI 12 Gy and methylprednisolone 60 mg/kg. The pt received tacrolimus as GVHD prophylaxis. The marrow was treated to deplete erythrocytes, granulocytes, plasma cells, NK cells, Tcells and B lymphocytes (Lym) leaving a population of GFC. The pt received a total of 1.20 × 106/kg CD34+ cells, 0.02 × 106/kg aβ; T cells and 0.08 × l06/kg S T cells. Neutrophil recovery occurred on day + 9 and platelet recovery on day + 19. In late January the patient noted shortness of breath. A chest x-ray demonstrated 2 nodules in the left upper lung field which had been present for 1-4 months. A CT scan of the chest showed nodules in the left and right upper lung fields. Samples from a fine needle aspiration grew ASP flavus. The patient was started on itraconazole (IT) therapy at 200 mg PO BID.In April he had normal immunoglobulin (Ig) levels. Results of RFLP at day +100 showed that the pts. cells were 100% donor. On day +100 he had a WBC count of 11,700 with 9% Lym; 25% CD4+ and 24% were CD8+ the CD4/CD8 ratio was normal at 1.02. One month after beginning IT. a repeat CT scan showed shrinking of all lesions. A prolonged period of immunodefiency is seen in patients who receive MUD BMT. The use of T-cell depleted BMT has had a positive effect on decreasing the incidence of GVHD but has resulted in an increase in graft failure and immunodefiency. Our pt achieved neutrophil engraftment on day +9, had normal Ig levels 5 months post BMT and a normal CD4/CD8 ratio at day+100. To our knowledge this is the first case report of successful treatment of invasive ASP in a pt who underwent a Tcell depleted MUD BMT with itraconazole therapy alone. The early reconstitution of immune function leads us to believe that the method used to manipulate the graft, facilitated engraftment and prevented the development of an overwhelming fungal infection.

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