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Etanercept for Late Onset Idiopathic Pneumonia Syndrome
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
537 Etanercept for Late Onset Idiopathic Pneumonia Syndrome Jonathan Robert Thompson 1, William Drobyski 2, Anita D’Souza 3, Timothy S. Fenske 1, Mehdi Hamadani 4, Parameswaran N. Hari 5, Marcelo C. Pasquini 6, Wael Saber 5, J. Douglas Rizzo 7. 1 Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI; 2 Dept of Medicine, Medical College of Wisconsin, Milwaukee, WI; 3 Division of Hematology/ Oncology, Medical College of Wisconsin, Milwaukee, WI; 4 Medicine, Hematology/Oncology, West Virginia University Mary Babb Randolph Cancer Center, Morgantown, WV; 5 Department of Medicine, CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI; 6 CIBMTR, CIBMTR (Center fo, Milwaukee, WI; 7 Department of Medicine, CIBMTR and Medical College of Wisconsin, Milwaukee, WI Idiopathic Pneumonia Syndrome (IPS) is a non-infectious, alveolar lung injury that typically occurs within the first 28 days after allogeneic hematopoietic cell transplant (HCT) and carries a high mortality. TNF-alpha is thought to play a significant role in the pathogenesis of the disease. Moreover, the TNF-alpha binding protein, etanercept, has been employed for treatment of this condition, and a number of small retrospective and prospective studies have shown clinical responses and survival benefits in IPS. Some patients, however, develop acute, non-infectious pulmonary damage later (>100 days) after HCT, and whether TNF-alpha blockade is beneficial in these patients has not been well addressed. The purpose of our current study was to better define the efficacy of etanercept in late onset IPS. Between 2004 and 2015, 22 patients at our center developed IPS more than 100 days after HCT and were treated with etanercept. IPS was diagnosed a median of 240 days (range 104555) after HCT. Pulmonary symptoms preceded the diagnosis by a median of 19 days and radiographic evidence of IPS was present a median of 10 days prior to diagnosis. 63% of patients underwent lung biopsy, and organizing pneumonia was present in 50% of specimens, with the remainder showing diffuse alveolar damage. 59% received a matched-related donor HCT and the rest received matched-unrelated donor HCT. The stem cell source was peripheral blood in 82% and bone marrow in the rest. 64% of the conditioning regimens were myeloablative. Grades II-IV acute graft versus host disease occurred in 55% of patients and chronic GVHD occurred in 55%. Etanercept was administered twice weekly at a dose of 0.4 mg/kg for four weeks. Only 36% of patients received all 8 doses of etanercept due to the high percentage of patients who died prior to completing treatment. All patients also received high dose corticosteroids (2 mg/kg). A complete clinical response (resolution of oxygen requirements) with etanercept was attained in 41% of patients. Radiographically, only 14% of patients had complete resolution of disease. The cause of death was respiratory failure due to lung injury in 55% of patients. There were no infectious complications from treatment. The median overall survival after etanercept was 22 days (range 1-2183). One year overall survival was 41%. This is the largest case series of adults who received etanercept for late onset IPS to date. Complete clinical response was observed in slightly over one-third of patients. Notably, pulmonary symptoms and radiographic changes were present for nearly 2 weeks in the majority of patients prior to diagnosis of IPS. Thus, earlier recognition and diagnosis of IPS may have led to improved outcomes with etanercept. Alternatively, other pathophysiological mechanisms and
S359
inflammatory cytokine pathways may be operative in these patients and require novel therapeutic approaches for the treatment of this condition.
538 Isolated Acute Myeloid Leukemia (AML) Relapses in Pericardium after Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Gaurav Trikha 1, Maxim Norkin 2, John R. Wingard 2. 1 Hematology-Oncology, University of Florida, Gainesville, FL; 2 University of Florida, Gainesville, FL Isolated AML relapse in pericardium after HSCT is not described. We report a case series of such patients A 68-year-old male with high-grade myelodysplastic syndrome with normal karyotype received a reduced-intensityconditioning matched-unrelated donor (MUD) peripheral blood HSCT. He achieved complete remission and 100% donor chimersim on day 30 after HSCT. Shortly after he developed rapidly progressive pericardial effusion and the flow-cytometry of pericardial fluid revealed abundant amount of aberrant myeloblasts. Cytogenetic analysis revealed complex male karyotype. A concurrent bone marrow biopsy showed no morphologic evidence of myeloid malignancy, but revealed similar complex karyotype. Patient received intensive re-induction chemotherapy but died on day 12 from septic shock. Another patient, a 39 year old male, who received MUD HSCT with cyclophosphamide and total body radiation conditioning for AML with monosomal karyotype. Nine years after HSCT he developed testicular relapse treated with local radiation-therapy and donor-lymphocyte-infusion (DLI). Seven months after DLI the patient presented with large pericardial effusion. Immunohistochemistry of pericardial fluid showed the presence of malignant myeloblasts and cytogenetic analysis showed again the presence of monsosomal karyotype. The concurrent bone marrow biopsy showed 40% cellularity with no morphologic evidence of AML including normal cytogenetics. He received reinduction with high-dose cytarabine and achieved another remission. Conclusion: To our knowledge this is the first report of isolated AML relapse in the pericardial space post-HSCT. Interestingly, both patients developed isolated relapse in pericardium effusion without overt AML in the bone marrow or other extra medullar spaces. Historically, cytotoxic CD8 positive T cells are seen in lower concentrations in soft tissues other than bone marrow, which may explain a higher possibility for extra-medullary relapses after HSCT. Pericardial space might be a sanctuary site that is able to evade the effect of graft-versus-leukemia effect and in time able to cause systemic relapse.
539 Concurrent Use of Blinatumomab and Donor Lymphocyte Infusion (DLI) for Treatment of Relapsed Precursor B Cell Acute Lymphoblastic Leukemia (pre B ALL) after Allogeneic Hematopoietic Cell Transplant (HCT) Masumi Ueda, Hillard M. Lazarus, Benjamin Tomlinson, Richard Creger, Merle Kolk, Marcos de Lima, Brenda Cooper. Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH Adults with relapsed pre B ALL after allogeneic HCT historically have poor prognosis, but new therapies may improve
537 Etanercept for Late Onset Idiopathic Pneumonia Syndrome Jonathan Robert Thompson 1, William Drobyski 2, Anita D’Souza 3, Timothy S. Fenske 1, Mehdi Hamadani 4, Parameswaran N. Hari 5, Marcelo C. Pasquini 6, Wael Saber 5, J. Douglas Rizzo 7. 1 Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI; 2 Dept of Medicine, Medical College of Wisconsin, Milwaukee, WI; 3 Division of Hematology/ Oncology, Medical College of Wisconsin, Milwaukee, WI; 4 Medicine, Hematology/Oncology, West Virginia University Mary Babb Randolph Cancer Center, Morgantown, WV; 5 Department of Medicine, CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI; 6 CIBMTR, CIBMTR (Center fo, Milwaukee, WI; 7 Department of Medicine, CIBMTR and Medical College of Wisconsin, Milwaukee, WI Idiopathic Pneumonia Syndrome (IPS) is a non-infectious, alveolar lung injury that typically occurs within the first 28 days after allogeneic hematopoietic cell transplant (HCT) and carries a high mortality. TNF-alpha is thought to play a significant role in the pathogenesis of the disease. Moreover, the TNF-alpha binding protein, etanercept, has been employed for treatment of this condition, and a number of small retrospective and prospective studies have shown clinical responses and survival benefits in IPS. Some patients, however, develop acute, non-infectious pulmonary damage later (>100 days) after HCT, and whether TNF-alpha blockade is beneficial in these patients has not been well addressed. The purpose of our current study was to better define the efficacy of etanercept in late onset IPS. Between 2004 and 2015, 22 patients at our center developed IPS more than 100 days after HCT and were treated with etanercept. IPS was diagnosed a median of 240 days (range 104555) after HCT. Pulmonary symptoms preceded the diagnosis by a median of 19 days and radiographic evidence of IPS was present a median of 10 days prior to diagnosis. 63% of patients underwent lung biopsy, and organizing pneumonia was present in 50% of specimens, with the remainder showing diffuse alveolar damage. 59% received a matched-related donor HCT and the rest received matched-unrelated donor HCT. The stem cell source was peripheral blood in 82% and bone marrow in the rest. 64% of the conditioning regimens were myeloablative. Grades II-IV acute graft versus host disease occurred in 55% of patients and chronic GVHD occurred in 55%. Etanercept was administered twice weekly at a dose of 0.4 mg/kg for four weeks. Only 36% of patients received all 8 doses of etanercept due to the high percentage of patients who died prior to completing treatment. All patients also received high dose corticosteroids (2 mg/kg). A complete clinical response (resolution of oxygen requirements) with etanercept was attained in 41% of patients. Radiographically, only 14% of patients had complete resolution of disease. The cause of death was respiratory failure due to lung injury in 55% of patients. There were no infectious complications from treatment. The median overall survival after etanercept was 22 days (range 1-2183). One year overall survival was 41%. This is the largest case series of adults who received etanercept for late onset IPS to date. Complete clinical response was observed in slightly over one-third of patients. Notably, pulmonary symptoms and radiographic changes were present for nearly 2 weeks in the majority of patients prior to diagnosis of IPS. Thus, earlier recognition and diagnosis of IPS may have led to improved outcomes with etanercept. Alternatively, other pathophysiological mechanisms and
S359
inflammatory cytokine pathways may be operative in these patients and require novel therapeutic approaches for the treatment of this condition.
538 Isolated Acute Myeloid Leukemia (AML) Relapses in Pericardium after Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Gaurav Trikha 1, Maxim Norkin 2, John R. Wingard 2. 1 Hematology-Oncology, University of Florida, Gainesville, FL; 2 University of Florida, Gainesville, FL Isolated AML relapse in pericardium after HSCT is not described. We report a case series of such patients A 68-year-old male with high-grade myelodysplastic syndrome with normal karyotype received a reduced-intensityconditioning matched-unrelated donor (MUD) peripheral blood HSCT. He achieved complete remission and 100% donor chimersim on day 30 after HSCT. Shortly after he developed rapidly progressive pericardial effusion and the flow-cytometry of pericardial fluid revealed abundant amount of aberrant myeloblasts. Cytogenetic analysis revealed complex male karyotype. A concurrent bone marrow biopsy showed no morphologic evidence of myeloid malignancy, but revealed similar complex karyotype. Patient received intensive re-induction chemotherapy but died on day 12 from septic shock. Another patient, a 39 year old male, who received MUD HSCT with cyclophosphamide and total body radiation conditioning for AML with monosomal karyotype. Nine years after HSCT he developed testicular relapse treated with local radiation-therapy and donor-lymphocyte-infusion (DLI). Seven months after DLI the patient presented with large pericardial effusion. Immunohistochemistry of pericardial fluid showed the presence of malignant myeloblasts and cytogenetic analysis showed again the presence of monsosomal karyotype. The concurrent bone marrow biopsy showed 40% cellularity with no morphologic evidence of AML including normal cytogenetics. He received reinduction with high-dose cytarabine and achieved another remission. Conclusion: To our knowledge this is the first report of isolated AML relapse in the pericardial space post-HSCT. Interestingly, both patients developed isolated relapse in pericardium effusion without overt AML in the bone marrow or other extra medullar spaces. Historically, cytotoxic CD8 positive T cells are seen in lower concentrations in soft tissues other than bone marrow, which may explain a higher possibility for extra-medullary relapses after HSCT. Pericardial space might be a sanctuary site that is able to evade the effect of graft-versus-leukemia effect and in time able to cause systemic relapse.
539 Concurrent Use of Blinatumomab and Donor Lymphocyte Infusion (DLI) for Treatment of Relapsed Precursor B Cell Acute Lymphoblastic Leukemia (pre B ALL) after Allogeneic Hematopoietic Cell Transplant (HCT) Masumi Ueda, Hillard M. Lazarus, Benjamin Tomlinson, Richard Creger, Merle Kolk, Marcos de Lima, Brenda Cooper. Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH Adults with relapsed pre B ALL after allogeneic HCT historically have poor prognosis, but new therapies may improve