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Immune Reconstitution after Alemtuzumab, Fludarabine, and Melphalan Reduced Intensity Conditioning
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
S163
Figure 1. T-cell subsets at 120 ± 30 days post-TCD PBSCT by CMV serostatus and viremia within 60 days of transplant.
2 Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital, Cincinnati, OH
Figure 2. Total CD8 cells by CMV serostatus and viremia within 60 days of TCD PBSCT.
Figure 3. CD8 effector memory cells by CMV serostatus and viremia within 60 days of TCD PBSCT.
by early CMV reactivation, clinical and subclinical, with the robustness of this response informing efficiency of viral clearance.
203 Immune Reconstitution after Alemtuzumab, Fludarabine, and Melphalan Reduced Intensity Conditioning Pauline A. Daniels 1, Jack Bleesing 1, Sharat Chandra 1, Christopher E. Dandoy 1, Stella M. Davies 1, Javier El-Bietar 1, Michael S. Grimley 1, Sonata Jodele 1, Michael B. Jordan 2, Pooja Khandelwal 1, Ashish Kumar 1, Parinda A. Mehta 1, Kasiani C. Myers 1, Adam S. Nelson 1, Rebecca A. Marsh 1. 1 Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH;
Background: Reduced intensity conditioning (RIC) regimens are frequently used in hematopoietic stem cell transplantation (HSCT) for patients with metabolic diseases, primary immune deficiencies, and bone marrow failure syndromes. We performed a retrospective analysis of immune reconstitution following RIC HSCT with alemtuzumab, fludarabine, and melphalan in 200 patients. Methods: We analyzed the medical records of 200 patients with non-malignant diseases who received RIC HSCT between August 2004-May 2013. Underlying diagnoses were metabolic diseases (n = 19), primary immune deficiencies (n = 159), and marrow failure syndromes (n = 22). Alemtuzumab was given as proximal (n = 52), distal (n = 71), intermediate (n = 63), and other schedules (n = 14). Fludarabine dose was 150 mg/ m2 (1 mg/kg in patients <10 kg). Melphalan dose was 140 mg/ m2 (4.7 mg/kg in patients <10 kg). Thirty-six patients received a 10/10 related donor graft, 110 patients received a 10/10 unrelated donor graft, and 54 patients received a graft from a mismatched donor. One hundred and eighty-two patients received stem cells from bone marrow, 8 received a peripheral blood stem cell graft, and 10 patients received a cord blood graft. GVHD prophylaxis consisted of methylprednisolone plus either cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil, +/- methotrexate. The absolute numbers of CD4+ T cells, CD8+ T cells, B cells and NK cells, PHA responsiveness, and IgA and IgM levels were collected. Results are reported as medians and ranges or 5th-95th percentiles. Results: NK cell recovery occurred by 100 days following HSCT with a median cell count of 187 cells/mcL at Day +100 (Figure 1). Median CD4 + and CD8 + T cell counts were 40 and 75 cells/mcL, 622 and 447.5 cells/mcL, and 949 and 590 cells/ mcL at 100 days, 1 year, and 2 years following RIC HSCT, respectively (Figure 1). The percentages of CD4 + and CD8 + T cells expressing CD45RA were 1.05% and 10.4%, 46.9% and 54.2%, and 55% and 66.2% at 100 days, 1 year, and 2 years following RIC HSCT, respectively (Figure 1). Median value for PHA responsiveness at one year was 123,680 (range 7905-337,890). Median B cell recovery at 100 days, 1 year, 2 years, and 5 years following RIC HSCT was 7.5 cells/mcL, 273 cells/mcL, 444.5 cells/mcL, and 338 cells/mcL, respectively (Figure 1). Median IgA levels at 100 days, 1 year, 2 years, and 5 years following RIC HSCT were 19.7 mg/dL, 37.5 mg/dL, 48.7 mg/dL, and 117.5 mg/dL, respectively. Conclusions: NK cell recovery occurs quickly while T and B cell reconstitution does not occur for 1-2 years in the majority of patients following RIC HSCT with alemtuzumab, fludarabine, and melphalan. These findings suggest that careful immune reconstitution monitoring should be performed for patients who receive RIC HSCT, as anti-microbial prophylaxis and IVIG may be needed for extended periods of time.
S163
Figure 1. T-cell subsets at 120 ± 30 days post-TCD PBSCT by CMV serostatus and viremia within 60 days of transplant.
2 Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital, Cincinnati, OH
Figure 2. Total CD8 cells by CMV serostatus and viremia within 60 days of TCD PBSCT.
Figure 3. CD8 effector memory cells by CMV serostatus and viremia within 60 days of TCD PBSCT.
by early CMV reactivation, clinical and subclinical, with the robustness of this response informing efficiency of viral clearance.
203 Immune Reconstitution after Alemtuzumab, Fludarabine, and Melphalan Reduced Intensity Conditioning Pauline A. Daniels 1, Jack Bleesing 1, Sharat Chandra 1, Christopher E. Dandoy 1, Stella M. Davies 1, Javier El-Bietar 1, Michael S. Grimley 1, Sonata Jodele 1, Michael B. Jordan 2, Pooja Khandelwal 1, Ashish Kumar 1, Parinda A. Mehta 1, Kasiani C. Myers 1, Adam S. Nelson 1, Rebecca A. Marsh 1. 1 Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH;
Background: Reduced intensity conditioning (RIC) regimens are frequently used in hematopoietic stem cell transplantation (HSCT) for patients with metabolic diseases, primary immune deficiencies, and bone marrow failure syndromes. We performed a retrospective analysis of immune reconstitution following RIC HSCT with alemtuzumab, fludarabine, and melphalan in 200 patients. Methods: We analyzed the medical records of 200 patients with non-malignant diseases who received RIC HSCT between August 2004-May 2013. Underlying diagnoses were metabolic diseases (n = 19), primary immune deficiencies (n = 159), and marrow failure syndromes (n = 22). Alemtuzumab was given as proximal (n = 52), distal (n = 71), intermediate (n = 63), and other schedules (n = 14). Fludarabine dose was 150 mg/ m2 (1 mg/kg in patients <10 kg). Melphalan dose was 140 mg/ m2 (4.7 mg/kg in patients <10 kg). Thirty-six patients received a 10/10 related donor graft, 110 patients received a 10/10 unrelated donor graft, and 54 patients received a graft from a mismatched donor. One hundred and eighty-two patients received stem cells from bone marrow, 8 received a peripheral blood stem cell graft, and 10 patients received a cord blood graft. GVHD prophylaxis consisted of methylprednisolone plus either cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil, +/- methotrexate. The absolute numbers of CD4+ T cells, CD8+ T cells, B cells and NK cells, PHA responsiveness, and IgA and IgM levels were collected. Results are reported as medians and ranges or 5th-95th percentiles. Results: NK cell recovery occurred by 100 days following HSCT with a median cell count of 187 cells/mcL at Day +100 (Figure 1). Median CD4 + and CD8 + T cell counts were 40 and 75 cells/mcL, 622 and 447.5 cells/mcL, and 949 and 590 cells/ mcL at 100 days, 1 year, and 2 years following RIC HSCT, respectively (Figure 1). The percentages of CD4 + and CD8 + T cells expressing CD45RA were 1.05% and 10.4%, 46.9% and 54.2%, and 55% and 66.2% at 100 days, 1 year, and 2 years following RIC HSCT, respectively (Figure 1). Median value for PHA responsiveness at one year was 123,680 (range 7905-337,890). Median B cell recovery at 100 days, 1 year, 2 years, and 5 years following RIC HSCT was 7.5 cells/mcL, 273 cells/mcL, 444.5 cells/mcL, and 338 cells/mcL, respectively (Figure 1). Median IgA levels at 100 days, 1 year, 2 years, and 5 years following RIC HSCT were 19.7 mg/dL, 37.5 mg/dL, 48.7 mg/dL, and 117.5 mg/dL, respectively. Conclusions: NK cell recovery occurs quickly while T and B cell reconstitution does not occur for 1-2 years in the majority of patients following RIC HSCT with alemtuzumab, fludarabine, and melphalan. These findings suggest that careful immune reconstitution monitoring should be performed for patients who receive RIC HSCT, as anti-microbial prophylaxis and IVIG may be needed for extended periods of time.