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Cardiac Risk Factors and Echocardiographic Variables As Predictors of Mortality in Bone Marrow Transplant Patients
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
S307
Patient Outcomes, % (n)
CSP/MMF
Low ALC30(n ¼ 17)
High ALC30 (n ¼ 27)
FK/MTX
Low ALC30 (n ¼ 0) High ALC30 (n ¼ 10)
Graft source
aGVHD, GradesI-IV
aGVHD, GradesIII-IV
Deaths by days 100(GVHD)*
Deaths by 6 months(GVHD)*
100-day survival
6-month survival
PB sib: 1 PB MUD: 8 BM MUD: 8 PB sib: 13 PB MUD: 13 BM MUD: 1 n/a PB sib: 3 PB MUD: 6 BM MUD: 1
100% (17)
65% (11)
35% (6)
47% (8)
65% (11)
53% (9)
67% (18)
18% (5)
7% (2)
15% (4)
92% (25)
70% (19)
n/a 30% (3)
n/a 0% (0)
n/a 0% (0)
n/a 0% (0)
n/a 90% (9)
n/a 80% (8)
Abbreviations: PB ¼ peripheral blood. BM ¼ bone marrow, MUD ¼ matched unrelated donor, sib ¼ sibling; *, deaths due to GVHD
Kristy Martin, Cindy Kramer, Molly Schneider, Valeriy Sedov, Juan Carlos Varela, Elizabeth J. Williams, Robert Stuart, Saurabh Chhabra. Blood and Marrow Transplant Program, Medical University of South Carolina, Charleston, SC Background: Previous reports have shown a correlation between day 30 absolute lymphocyte count (ALC30) after allogeneic hematopoietic cell transplantation (alloHCT) and patient outcomes. These reports included patients with various conditioning regimens and reported decreased overall survival and increased acute Graft-versus-Host disease (aGVHD) in patients with lower ALC30. The objective of this study was to find correlation between ALC30 and outcomes after alloHCT using reduced intensity conditioning (RIC) of fludarabine (25mg/m2 IV/d d -5 to -1) and melphalan (70mg/m2 IV/d d -2 to -1) conditioning (Flu/Mel). Methods: A retrospective chart review of patients receiving RIC alloHCT from Jan 2012 to May 2015 was conducted. Patients received cyclosporine/mycophenolate mofetil (CSP/ MMF) or tacrolimus/methotrexate (FK/MTX) for GVHD prophylaxis. The indications for alloHCT were AML (40), MDS (7), CML (2), ALL (3), NHL (1) and HL (1). Only patients who had one alloHCT using T cell-replete graft were included. Results: Fifty four patients were analyzed; of these, 17 had ALC30 lower than 400x106/L. With a median follow-up of
11.8 months, the day 100 and 6 month survival were 65% and 53% for the low ALC30 group and 92% and 73% for the high ALC30 group. Of the 54 patients, 44 received CSP/MMF (median follow-up 17.5 months) and 10 had FK/MTX (median follow-up 9.8 months). None of the FK/MTX patients had low ALC30 while 17 of 44 (39%) CSP/MMF patients did. There were seven deaths before d100 in the low ALC30 group, all due to aGVHD. Of the three deaths before d100 in the high ALC30 group, two were due to aGVHD and one due to infection. Eleven patients (65%) in the low ALC30 group had Grade III-IV aGVHD compared to five (14%) in the high group. None of the FK/MTX patients had GIII-IV aGVHD compared to 36% of the CSP/MMF patients. Five patients relapsed, all of whom received CSP/MMF and had high ALC30. Overall survival at d100 and 6 months was 90% (9/10) and 80% (8/10) for the FK/MTX group compared to 82% (36/44) and 64% (28/44) for the CSP/MMF group, respectively. Conclusion: Post-transplant day 30 ALC over 400x106/L is predictive of lower incidence of Grade III-IV aGVHD and lower risk of early mortality, regardless of the GVHD prophylaxis in patients receiving RIC (Flu/Mel) allogeneic transplantation.
453 Cardiac Risk Factors and Echocardiographic Variables As Predictors of Mortality in Bone Marrow Transplant Patients Neeraj Saini 1, Zheng Zhou 2, Kinan Yarta3, Carol Mathew4, Muthalagu Ramanathan 2, Rajneesh Nath 2, Jan Cerny 5. 1 Division of Hematology/Oncology, University Of Massachusetts, Worcester, MA; 2 Section BMT, Division of Hematology/Oncology, University of Massachusetts, Worcester, MA; 3 Internal Medicine, NYU Lutheran, New york, NY; 4 Internal Medicine, University of Massachussetts, Worcester, MA; 5 Department of Medicine; Division of Hematology/ Oncology, University of Massachusetts, Worcester, MA Background: The pre-Bone marrow transplant (BMT) evaluation of cardiac function by echocardiographically measured left ventricular ejection fraction (LVEF) is one of the fitness criteria. However, the data documenting the usefulness of such criteria are sparse. The aim of our study is to investigate whether pre-transplant cardiac risk factors and echocardiographic parameters could predict survival/mortality in BMT patients.
S308
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
3
Apollo Gleanagles hospital, kolkata, India; 4 Tata Medical centre, kolkata, India; 5 Haematology and stem cell transplant, AMRI hospitals, kolkata, India
Methods: We retrospectively reviewed consecutive patients undergoing BMT at our institution from January 2009 to December 2012. We compared clinical outcome in patients with regards to cardiac risk factors (history of coronary artery disease (CAD), myocardial infarction (MI), arrhythmias, Heart failure (HF), smoking, hyperlipidemia and diabetes mellitus) and multiple parameters from pre-transplant Echo. Echo variables were Left ventricular in Diastole diameter (LVIDd), Left Atrium size (LA), Left Ventricular Mass (LVM), Left ventricular mass index (LVMI), Relative wall thickness (RWT) and left ventricular geometry/remodeling. Survival was defined as months from BMT to death or the most recent follow-up. Patient’s whose Echo images were of poor quality or couldn’t be located in the system were excluded from the study. Results: Of the 208 eligible patients (86 females, 41%), 121 (58%) patients underwent autologous transplant and 87 (42%) patients had an allogeneic transplant, respectively. The mean age was 56.9 years (range, 19-83 years). The prevalence of CAD, MI, CHF and history of arrhythmia in our cohort was approximately 35 (17%), 16 (7%), 16 (8%) and 17 (9%) respectively. Fourteen (7%) patients had LVEF less than 50% and 194 (93%) patients had LVEF >¼ 50%. History of cardiac arrhythmias showed borderline significance for association with mortality with a hazard ratio (HR) of 1.88(p¼0.0534) compared to no history of arrhythmia. Patients with history of CAD and CHF showed a trend toward increased mortality, albeit did not reach statistical significance. Decreased LVEF <50% also showed a trend toward increased mortality compared to patients with normal EF with a HR of 2.025 (p ¼ 0.0835). Other Echocardiography variables such as LVMI, RWT, Left ventricular geometry and LA size did not show any statistical correlation with mortality in BMT patients. Conclusion: Our results further support that BMT patients with significant cardiac risk factors are at increased risk of mortality. In particular, decreased LV ejection fraction <50% and history of arrhythmia are predictors of mortality in BMT patient. All patient’s cardiac status should be well optimized prior to transplant.
454 Total Marrow Irradiation (TMI) Based T- Replete Myeloablative Haploidentical Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in Second Complete Remission: A Single Center Experience of Two Cases Neelesh Jain1, Amitabh Ray2, Amrita Chakravarti3, Kasturi Sengupta4, Joydeep Chakrabartty 5. 1 apollo Glenagles hospital, kolkata, India; 2 AMRI hospitals, Kolkata, India;
Background: Total body irradiation (TBI), currently has selected use in stem cell transplant due to significant extrahematologic toxicity. Intensity modulated total marrow irradiation (TMI) represents an innovative technique to selectively irradiate the bone marrow with much less extrahematological toxicities. We combined a fully myeloablative chemotherapy regimen with TMI of 900 cGY in two patients with relapsed ALL with good results. Materials and Methods: Two male patients of relapsed T-ALL who have previously received eight cycles of Hyper CVAD chemotherapy, brought into remission for about 7 months followed by systemic relapse. After that 2 cycles of nelarabine (1500mg/m2) was given to bring into the remission followed by haplo identical stem cell transplantation with following details: total marrow irradiation (TMI) based myeloablative preparative regimen, Anti thymocyte globulin-and Total marrow irradiation (TMI) - [total dose 900 cGY]) was given followed by infusion of unmanipulated peripheral blood stem cells on day “0” from father in both cases without any blood group mismatch. Donor specific antibodies were also not found. GVHD prophylaxis regime used was Cyclosporine A, Bortezomib (1.3mg/m2 body weight) on D +1 and D+3, Cyclophosphamide (50mg/Kg body weight on Day +4 and Day +5 with MESNA and Mycofenolate Mofetil. Median patient age was 20.5 years. Patients received antimicrobial prophylaxis along with an initial pentamidine nebulization as Pneumocystis carinii (PCP) prophylaxis, followed by Septran (sulfamethoxazole + trimethoprim) after engraftment. Total Marrow Irradiation (TMI) details Volumetric Modulated Arc Therapy planning was performed using RapidArc technology. The planning target volume consisted of all the bones in the body from the head to the femur, and the humerus, plus a 3.0-mm margin. The VMAT-TMI technique consisted of three plans: the head and neck, the chest, and the pelvis using appropriate arcs. The plans were prescribed to ensure 95% planning target volume dose coverage with the prescription dose. Results: Both patients engrafted with a median time to neutrophil and platelet recovery of 15 and 22 days, respectively. During this course patient developed neutropenic sepsis which was adequately managed with broad spectrum IV antibiotics. One of the patient grown ESBL Klebsiella in urine, and the other one showed MDR Klebsiella in blood. Both of them achieved sustained complete donor whole blood chimerism by day +30. Acute graft-versus-host disease (GVHD) grades II to III was seen in one but no chronic GVHD is seen till now i.e. after a median follow-up of 14 months. Both the patients are doing fine so far. Conclusion: Myeloablative haploidentical transplantation using total marrow irradiation (TMI) based regimen is a valid option for patients with advanced hematologic malignancies with reduced risk of extra-hematologic toxicity.
455 Pre-Transplant Ferritin, Albumin and Hemoglobin Are Predictive Biomarkers of Survival Outcome Adding Prognostic Value to Disease Risk Index Following Allogeneic Stem Cell Transplantation Lynette Chui Yen Chee 1, Mark Tacey 2, 3, Bernice Lim3, Andrew Boon Ming Lim 4, Jeffrey Szer 5, David Stuart Ritchie 5, 6. 1 Department of Clinical Haematology and BMT Service, The
S307
Patient Outcomes, % (n)
CSP/MMF
Low ALC30(n ¼ 17)
High ALC30 (n ¼ 27)
FK/MTX
Low ALC30 (n ¼ 0) High ALC30 (n ¼ 10)
Graft source
aGVHD, GradesI-IV
aGVHD, GradesIII-IV
Deaths by days 100(GVHD)*
Deaths by 6 months(GVHD)*
100-day survival
6-month survival
PB sib: 1 PB MUD: 8 BM MUD: 8 PB sib: 13 PB MUD: 13 BM MUD: 1 n/a PB sib: 3 PB MUD: 6 BM MUD: 1
100% (17)
65% (11)
35% (6)
47% (8)
65% (11)
53% (9)
67% (18)
18% (5)
7% (2)
15% (4)
92% (25)
70% (19)
n/a 30% (3)
n/a 0% (0)
n/a 0% (0)
n/a 0% (0)
n/a 90% (9)
n/a 80% (8)
Abbreviations: PB ¼ peripheral blood. BM ¼ bone marrow, MUD ¼ matched unrelated donor, sib ¼ sibling; *, deaths due to GVHD
Kristy Martin, Cindy Kramer, Molly Schneider, Valeriy Sedov, Juan Carlos Varela, Elizabeth J. Williams, Robert Stuart, Saurabh Chhabra. Blood and Marrow Transplant Program, Medical University of South Carolina, Charleston, SC Background: Previous reports have shown a correlation between day 30 absolute lymphocyte count (ALC30) after allogeneic hematopoietic cell transplantation (alloHCT) and patient outcomes. These reports included patients with various conditioning regimens and reported decreased overall survival and increased acute Graft-versus-Host disease (aGVHD) in patients with lower ALC30. The objective of this study was to find correlation between ALC30 and outcomes after alloHCT using reduced intensity conditioning (RIC) of fludarabine (25mg/m2 IV/d d -5 to -1) and melphalan (70mg/m2 IV/d d -2 to -1) conditioning (Flu/Mel). Methods: A retrospective chart review of patients receiving RIC alloHCT from Jan 2012 to May 2015 was conducted. Patients received cyclosporine/mycophenolate mofetil (CSP/ MMF) or tacrolimus/methotrexate (FK/MTX) for GVHD prophylaxis. The indications for alloHCT were AML (40), MDS (7), CML (2), ALL (3), NHL (1) and HL (1). Only patients who had one alloHCT using T cell-replete graft were included. Results: Fifty four patients were analyzed; of these, 17 had ALC30 lower than 400x106/L. With a median follow-up of
11.8 months, the day 100 and 6 month survival were 65% and 53% for the low ALC30 group and 92% and 73% for the high ALC30 group. Of the 54 patients, 44 received CSP/MMF (median follow-up 17.5 months) and 10 had FK/MTX (median follow-up 9.8 months). None of the FK/MTX patients had low ALC30 while 17 of 44 (39%) CSP/MMF patients did. There were seven deaths before d100 in the low ALC30 group, all due to aGVHD. Of the three deaths before d100 in the high ALC30 group, two were due to aGVHD and one due to infection. Eleven patients (65%) in the low ALC30 group had Grade III-IV aGVHD compared to five (14%) in the high group. None of the FK/MTX patients had GIII-IV aGVHD compared to 36% of the CSP/MMF patients. Five patients relapsed, all of whom received CSP/MMF and had high ALC30. Overall survival at d100 and 6 months was 90% (9/10) and 80% (8/10) for the FK/MTX group compared to 82% (36/44) and 64% (28/44) for the CSP/MMF group, respectively. Conclusion: Post-transplant day 30 ALC over 400x106/L is predictive of lower incidence of Grade III-IV aGVHD and lower risk of early mortality, regardless of the GVHD prophylaxis in patients receiving RIC (Flu/Mel) allogeneic transplantation.
453 Cardiac Risk Factors and Echocardiographic Variables As Predictors of Mortality in Bone Marrow Transplant Patients Neeraj Saini 1, Zheng Zhou 2, Kinan Yarta3, Carol Mathew4, Muthalagu Ramanathan 2, Rajneesh Nath 2, Jan Cerny 5. 1 Division of Hematology/Oncology, University Of Massachusetts, Worcester, MA; 2 Section BMT, Division of Hematology/Oncology, University of Massachusetts, Worcester, MA; 3 Internal Medicine, NYU Lutheran, New york, NY; 4 Internal Medicine, University of Massachussetts, Worcester, MA; 5 Department of Medicine; Division of Hematology/ Oncology, University of Massachusetts, Worcester, MA Background: The pre-Bone marrow transplant (BMT) evaluation of cardiac function by echocardiographically measured left ventricular ejection fraction (LVEF) is one of the fitness criteria. However, the data documenting the usefulness of such criteria are sparse. The aim of our study is to investigate whether pre-transplant cardiac risk factors and echocardiographic parameters could predict survival/mortality in BMT patients.
S308
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
3
Apollo Gleanagles hospital, kolkata, India; 4 Tata Medical centre, kolkata, India; 5 Haematology and stem cell transplant, AMRI hospitals, kolkata, India
Methods: We retrospectively reviewed consecutive patients undergoing BMT at our institution from January 2009 to December 2012. We compared clinical outcome in patients with regards to cardiac risk factors (history of coronary artery disease (CAD), myocardial infarction (MI), arrhythmias, Heart failure (HF), smoking, hyperlipidemia and diabetes mellitus) and multiple parameters from pre-transplant Echo. Echo variables were Left ventricular in Diastole diameter (LVIDd), Left Atrium size (LA), Left Ventricular Mass (LVM), Left ventricular mass index (LVMI), Relative wall thickness (RWT) and left ventricular geometry/remodeling. Survival was defined as months from BMT to death or the most recent follow-up. Patient’s whose Echo images were of poor quality or couldn’t be located in the system were excluded from the study. Results: Of the 208 eligible patients (86 females, 41%), 121 (58%) patients underwent autologous transplant and 87 (42%) patients had an allogeneic transplant, respectively. The mean age was 56.9 years (range, 19-83 years). The prevalence of CAD, MI, CHF and history of arrhythmia in our cohort was approximately 35 (17%), 16 (7%), 16 (8%) and 17 (9%) respectively. Fourteen (7%) patients had LVEF less than 50% and 194 (93%) patients had LVEF >¼ 50%. History of cardiac arrhythmias showed borderline significance for association with mortality with a hazard ratio (HR) of 1.88(p¼0.0534) compared to no history of arrhythmia. Patients with history of CAD and CHF showed a trend toward increased mortality, albeit did not reach statistical significance. Decreased LVEF <50% also showed a trend toward increased mortality compared to patients with normal EF with a HR of 2.025 (p ¼ 0.0835). Other Echocardiography variables such as LVMI, RWT, Left ventricular geometry and LA size did not show any statistical correlation with mortality in BMT patients. Conclusion: Our results further support that BMT patients with significant cardiac risk factors are at increased risk of mortality. In particular, decreased LV ejection fraction <50% and history of arrhythmia are predictors of mortality in BMT patient. All patient’s cardiac status should be well optimized prior to transplant.
454 Total Marrow Irradiation (TMI) Based T- Replete Myeloablative Haploidentical Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in Second Complete Remission: A Single Center Experience of Two Cases Neelesh Jain1, Amitabh Ray2, Amrita Chakravarti3, Kasturi Sengupta4, Joydeep Chakrabartty 5. 1 apollo Glenagles hospital, kolkata, India; 2 AMRI hospitals, Kolkata, India;
Background: Total body irradiation (TBI), currently has selected use in stem cell transplant due to significant extrahematologic toxicity. Intensity modulated total marrow irradiation (TMI) represents an innovative technique to selectively irradiate the bone marrow with much less extrahematological toxicities. We combined a fully myeloablative chemotherapy regimen with TMI of 900 cGY in two patients with relapsed ALL with good results. Materials and Methods: Two male patients of relapsed T-ALL who have previously received eight cycles of Hyper CVAD chemotherapy, brought into remission for about 7 months followed by systemic relapse. After that 2 cycles of nelarabine (1500mg/m2) was given to bring into the remission followed by haplo identical stem cell transplantation with following details: total marrow irradiation (TMI) based myeloablative preparative regimen, Anti thymocyte globulin-and Total marrow irradiation (TMI) - [total dose 900 cGY]) was given followed by infusion of unmanipulated peripheral blood stem cells on day “0” from father in both cases without any blood group mismatch. Donor specific antibodies were also not found. GVHD prophylaxis regime used was Cyclosporine A, Bortezomib (1.3mg/m2 body weight) on D +1 and D+3, Cyclophosphamide (50mg/Kg body weight on Day +4 and Day +5 with MESNA and Mycofenolate Mofetil. Median patient age was 20.5 years. Patients received antimicrobial prophylaxis along with an initial pentamidine nebulization as Pneumocystis carinii (PCP) prophylaxis, followed by Septran (sulfamethoxazole + trimethoprim) after engraftment. Total Marrow Irradiation (TMI) details Volumetric Modulated Arc Therapy planning was performed using RapidArc technology. The planning target volume consisted of all the bones in the body from the head to the femur, and the humerus, plus a 3.0-mm margin. The VMAT-TMI technique consisted of three plans: the head and neck, the chest, and the pelvis using appropriate arcs. The plans were prescribed to ensure 95% planning target volume dose coverage with the prescription dose. Results: Both patients engrafted with a median time to neutrophil and platelet recovery of 15 and 22 days, respectively. During this course patient developed neutropenic sepsis which was adequately managed with broad spectrum IV antibiotics. One of the patient grown ESBL Klebsiella in urine, and the other one showed MDR Klebsiella in blood. Both of them achieved sustained complete donor whole blood chimerism by day +30. Acute graft-versus-host disease (GVHD) grades II to III was seen in one but no chronic GVHD is seen till now i.e. after a median follow-up of 14 months. Both the patients are doing fine so far. Conclusion: Myeloablative haploidentical transplantation using total marrow irradiation (TMI) based regimen is a valid option for patients with advanced hematologic malignancies with reduced risk of extra-hematologic toxicity.
455 Pre-Transplant Ferritin, Albumin and Hemoglobin Are Predictive Biomarkers of Survival Outcome Adding Prognostic Value to Disease Risk Index Following Allogeneic Stem Cell Transplantation Lynette Chui Yen Chee 1, Mark Tacey 2, 3, Bernice Lim3, Andrew Boon Ming Lim 4, Jeffrey Szer 5, David Stuart Ritchie 5, 6. 1 Department of Clinical Haematology and BMT Service, The