- Email: [email protected]
Acute Kidney Injury during Vancomycin Therapy Associated with Combination Use of Piperacillin-Tazobactam after Allogeneic Stem Cell Transplantation
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
S281
Results: Five patients met the inclusion criteria. Post-HCT follow-up ranged from 1 month to 3.6 years. All 5 patients are alive and in remission. Four of 5 patients underwent reduced intensity conditioning. While all patients engrafted, 60% (n = 3) became mixed chimera requiring treatment with donor lymphocyte infusions (DLI). One of 5 patients developed grade 1 acute graft-vs-host disease (GVHD) of the skin. One of 5 patients developed chronic GVHD (after DLI). No acute organ toxicities were reported. See Table 1 for further details. Discussion: Allogeneic HST appears to be a safe and curative option for relapsed/refractory ALCL after remission reinduction with CRZ monotherapy. Due to the development of mixed chimerism in 60% of our patients, myeloablative conditioning may be preferable.
385
Figure 1. Kaplan Meier survival curve.
Survival: Median follow up time was 22.8 months, 49.2 months and 23.7 months in FBu, FM and FBM groups, respectively (P = .34). The corresponding mean survival times were 46.6 months, 41.9 months and 43.3 months. Kaplan Meier survival curves are shown in Figure 1. Conclusions: Although FBM and FM have better chimerism results, rates of acute GVHD were higher in these groups. All three RIC regimens used for HSCT in patients with myelofibrosis have comparable overall survival.
384 Allogeneic Hematopoietic Cell Transplant Following Crizotinib Monotherapy for Relapsed/Refractory Anaplastic Large Cell Lymphoma Tami John 1, Ghadir Sasa 2, Stephen Gottschalk 2, Nabil Ahmed 2, Carl Allen 2, Bilal Omer 2, Meena Hegde 2, Swati Naik 2, Kathryn Leung 2, Caridad Martinez 2, Robert A. Krance 2. 1 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital Cancer Center, Houston, TX; 2 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX Background: Anaplastic large cell lymphoma (ALCL) comprises 20-30% of pediatric non-Hodgkin’s lymphoma cases with up to 90% exhibiting anaplastic lymphoma kinase (ALK) gene alterations. Cure rates approach 70-80% with conventional chemotherapy. Second remission for relapsed/refractory ALK+ ALCL is achievable with ALK inhibition via crizotinib (CRZ). We report on outcomes after allogeneic hematopoietic transplant (HST) for relapsed/refractory ALCL after CRZ. Methods: We performed a retrospective analysis of outcomes in children treated at Texas Children’s Hospital for relapsed/refractory ALCL. All patients who received allogeneic HCT after CRZ were included. Data regarding engraftment status, acute transplant related complications and disease-free-survival were collected.
Acute Kidney Injury during Vancomycin Therapy Associated with Combination Use of PiperacillinTazobactam after Allogeneic Stem Cell Transplantation Misato Kariya 1, Yoshimitsu Shimomura 2, Nobuhiro Hiramoto 2, Yutaka Okada 1, Ai Ootoshi 1, Haruka Maki 1, Hisako Hashimoto 2. 1 Department of Pharmacy, Foundation for Biomedical Research and Innovation, Kobe, Japan; 2 Department of Cell Therapy, Foundation for Biomedical Research and Innovation, Kobe, Japan Introduction: Infectious complications with gram-positive cocci are common in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Vancomycin (VCM) is frequently used to treat gram-positive organisms and has the strong risk for acute kidney injury (AKI). AKI after allogeneic HSCT was associated with poor outcomes. To reduce the risk of AKI after allogeneic HSCT, we analyzed the factor which may exacerbate AKI proceeding from VCM usage. Patients and Methods: A retrospective case analysis was performed for patients who were treated with vancomycin after allogeneic HSCT at our hospital from April 2013 to March 2016. We set the primary endpoint as an incidence of AKI defined as an increase in serum creatinine (sCr) of .5 mg/dL or 50% of baseline during vancomycin therapy. To evaluate the impact of each risk factor on the endpoint, we employed logistic regression analysis. The following factors were evaluated in this study: age, sex and high blood urea nitrogen (BUN)/sCrratio defined BUN/sCr of >20, high VCM trough defined as the max of VCM trough of >20 and combination use of piperacillin-tazobactam (PIPC/TAZ). Results: Fifty-eight patients were enrolled and analyzed in the present study. Median age was 46 (range 25 to 69) years old, and 32 patients were male. Among the study population, 37 patients had high BUN/sCr ratio, 13 patients had high VCM trough, and 13 patients received PIPC/TAZ. Regarding the incidence of the primary endpoint, there were 13 cases (22%) of AKI. In univariate analysis, high BUN/sCr ratio and
Table 1 #
Upfront Therapy
CRZ Duration (Months)
HLA
Conditioning
Follow-Up (Years)
Complications
GVHD
1 2 3 4 5
CHOP (8 cycles) ALCL-99 ALCL-99 NHL-BFM ALCL-99
22.5 2-3 7 3 3-4
MUD MRD MUD MRD MUD
Flu/alemtuzumab/600TBI Flu/ alemtuzumab/600TBI Flu/ alemtuzumab/600TBI Flu/ alemtuzumab/600TBI Cytarbine/cyclophos/alemtuzumab/1400TBI
3 3.3 3.5 3.6 1 month
Mixed Chimera (DLI x2) Mixed Chimera (DLI x4) None Mixed Chimera (DLI x 2) None
cGVHD None G1 aGVHD skin None None
S282
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
Table 1 Impact of Combination Drugs on Incidence of AKI Parameter
Age, per year Sex (Male) High BUN/sCr ratio High VCM trough Combination use of PIPC/TAZ
Univariate Analysis
Multivariate Analysis
HR(95%CI)
Pvalue
HR(95%CI)
Pvalue
.988 (.937-1.04) .417 (.117-1.48) 8.77 (1.05-73.3) 3.61 (.998-13.0) 3.96 (1.05-15.0)
.67 .18 .045 .05 .04
16.9 (1.36-209)
.03
6.73 (1.22-37.1)
.03
Results: Sixty-one patients were available for analysis: 16 in the myeloablative without r-ATG group, 16 in the myeloablative with r-ATG group, and 29 in the RIC control group. Only 14 patients in the group that utilized r-ATG as part of the conditioning regimen had mature 100-day data to utilize for analysis of the primary outcome. The incidence of CMV reactivation is increased with the use of r-ATG (25% vs. 43%). Data for 6-month and 12-month evaluation of incidence of GVHD is not yet mature, but a preliminary analysis shows a decrease in incidence of GVHD at 6 months (45% vs. 33%) and 12 months (44% vs. 20%), respectively, when r-ATG is utilized.
combination use of PIPC/TAZ was the significant factor of incidence of AKI (Table 1). Multivariate logistic regression analysis identified high BUN/sCr ratio and combination use of PIPC/TAZ as independently associated with the incidence of AKI (Table 1). Conclusion: Our study showed that high BUN/sCr and combination use of PIPC/TAZ were identified as risk factors of AKI in patients treated with VCM. Patients with these risk factors may require careful observation and avoid administration of PIPC/TAZ or consider to change the antibacterial drug.
386 Relationship of CMV Reactivation and Rabbit Antithymocyte Globulin Administration in Allogeneic Stem Cell Transplant Patients LeAnne Kennedy 1, Marie Cavalier 2, Dianna Howard 3. 1 Pharmacy, Wake Forest University Baptist Medical Center, Winston Salem, NC; 2 Pharmacy, Wake Forest Baptist Medical Center, Winston Salem, NC; 3 Hematology and Oncology, Wake Forest Comprehensive Cancer Center, Winston Salem, NC Background: Rabbit anti-thymocyte globulin (r-ATG) is widely used in the conditioning regimen before allogeneic stem cell transplant (SCT) in a number of disease settings, but largely in the context of unrelated donor or mismatched related donor transplants, to decrease the risk of graft-versus-host-disease (GVHD). Attempts to improve survival by the delivery of optimal therapy for the suppression of GVHD are thwarted by emergence of therapy-related infectious complications or primary disease relapse and offset any survival advantage. Cytomegalovirus (CMV) infections can be a significant factor in the post-transplant treatment related morbidity and mortality. R-ATG is associated with a delay in lymphocyte engraftment and prolonged time to absolute lymphocyte count (ALC) recovery, which has been implicated as a risk factor for CMV disease. Previously, only reduced intensity conditioning (RIC) matched unrelated donor (MUD) stem cell transplant recipients received GVHD prophylaxis with r-ATG. As of January 2015, both RIC MUD and fully myeloablative MUD transplants began receiving r-ATG as part of their conditioning regimen for GVHD prophylaxis. Objective: Determine if GVHD prophylaxis with r-ATG increased CMV reactivation 100 days post-transplant in patients who underwent a fully myeloablative MUD allogeneic stem cell transplant. The primary outcome will be the incidence of CMV at 100 days. Methods: This retrospective chart review evaluated patients who received a MUD allogeneic SCT from October 2012 to September 2016 at our institution. A group of RIC MUD patients will serve as a control, as these patients consistently received r-ATG for GVHD prophylaxis as part of their preparative regimen. To be included, patients received an allogeneic SCT from an unrelated donor for a hematologic malignancy and be at least 18 years of age.
Conclusions: Reactivation of CMV is increased when r-ATG is used as part of the conditioning regimen for GVHD prophylaxis. Mature data is still needed to determine the full benefit towards preventing GVHD.
387 Early Results of Phase II Study Using OMS721 in Patients with Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HCT-TMA) Samer K. Khaled 1, Yok Lam Kwong 2, Mark Smith 3, Ara Metjian 4, Steve Whitaker 5. 1 City of Hope, Duarte, CA; 2 Hong Kong University, Hong Kong, China; 3 Canterbury Health Laboratories, Christchurch, New Zealand; 4 Duke University School of Medicine, Durham, NC; 5 Omeros Corporation, Seattle, WA Introduction: TMA is a potentially life-threatening complication of HCT currently managed largely by amelioration of inciting factors including avoidance of calcineurininhibitors and treatment of ongoing infections, as well as supportive measures such as hemodialysis. Patients who do not respond have poor prognosis. Plasma exchange has not shown efficacy and no other therapy is approved. Complement activation has been reported in the pathogenesis of HCT-TMA. OMS721 is a human monoclonal IgG4 inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of complement activation. Here we report early results of OMS721 treatment in HCT-TMA patients. Methods: This is a Phase 2 uncontrolled, open-label, 3-stage study of OMS721 to assess safety, tolerability and clinical activity of OMS721 in patients with TMA (HCT-TMA, aHUS and TTP). Stage 1 included dose-escalation cohorts, Stage 2 expands disease-specific cohorts and Stage 3 provides optional extended treatment. For inclusion, patients with HCTTMA should demonstrate thrombocytopenia and evidence of microangiopathic hemolytic anemia, and at least 2 weeks must have elapsed since changes in immunosuppressive treatment. HCT-TMA patients received OMS721 X* mg/kg IV once weekly (Stage 1 up to 4 weeks and Stages 2 and 3 up to 8 * Dose is confidential.
S281
Results: Five patients met the inclusion criteria. Post-HCT follow-up ranged from 1 month to 3.6 years. All 5 patients are alive and in remission. Four of 5 patients underwent reduced intensity conditioning. While all patients engrafted, 60% (n = 3) became mixed chimera requiring treatment with donor lymphocyte infusions (DLI). One of 5 patients developed grade 1 acute graft-vs-host disease (GVHD) of the skin. One of 5 patients developed chronic GVHD (after DLI). No acute organ toxicities were reported. See Table 1 for further details. Discussion: Allogeneic HST appears to be a safe and curative option for relapsed/refractory ALCL after remission reinduction with CRZ monotherapy. Due to the development of mixed chimerism in 60% of our patients, myeloablative conditioning may be preferable.
385
Figure 1. Kaplan Meier survival curve.
Survival: Median follow up time was 22.8 months, 49.2 months and 23.7 months in FBu, FM and FBM groups, respectively (P = .34). The corresponding mean survival times were 46.6 months, 41.9 months and 43.3 months. Kaplan Meier survival curves are shown in Figure 1. Conclusions: Although FBM and FM have better chimerism results, rates of acute GVHD were higher in these groups. All three RIC regimens used for HSCT in patients with myelofibrosis have comparable overall survival.
384 Allogeneic Hematopoietic Cell Transplant Following Crizotinib Monotherapy for Relapsed/Refractory Anaplastic Large Cell Lymphoma Tami John 1, Ghadir Sasa 2, Stephen Gottschalk 2, Nabil Ahmed 2, Carl Allen 2, Bilal Omer 2, Meena Hegde 2, Swati Naik 2, Kathryn Leung 2, Caridad Martinez 2, Robert A. Krance 2. 1 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital Cancer Center, Houston, TX; 2 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX Background: Anaplastic large cell lymphoma (ALCL) comprises 20-30% of pediatric non-Hodgkin’s lymphoma cases with up to 90% exhibiting anaplastic lymphoma kinase (ALK) gene alterations. Cure rates approach 70-80% with conventional chemotherapy. Second remission for relapsed/refractory ALK+ ALCL is achievable with ALK inhibition via crizotinib (CRZ). We report on outcomes after allogeneic hematopoietic transplant (HST) for relapsed/refractory ALCL after CRZ. Methods: We performed a retrospective analysis of outcomes in children treated at Texas Children’s Hospital for relapsed/refractory ALCL. All patients who received allogeneic HCT after CRZ were included. Data regarding engraftment status, acute transplant related complications and disease-free-survival were collected.
Acute Kidney Injury during Vancomycin Therapy Associated with Combination Use of PiperacillinTazobactam after Allogeneic Stem Cell Transplantation Misato Kariya 1, Yoshimitsu Shimomura 2, Nobuhiro Hiramoto 2, Yutaka Okada 1, Ai Ootoshi 1, Haruka Maki 1, Hisako Hashimoto 2. 1 Department of Pharmacy, Foundation for Biomedical Research and Innovation, Kobe, Japan; 2 Department of Cell Therapy, Foundation for Biomedical Research and Innovation, Kobe, Japan Introduction: Infectious complications with gram-positive cocci are common in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Vancomycin (VCM) is frequently used to treat gram-positive organisms and has the strong risk for acute kidney injury (AKI). AKI after allogeneic HSCT was associated with poor outcomes. To reduce the risk of AKI after allogeneic HSCT, we analyzed the factor which may exacerbate AKI proceeding from VCM usage. Patients and Methods: A retrospective case analysis was performed for patients who were treated with vancomycin after allogeneic HSCT at our hospital from April 2013 to March 2016. We set the primary endpoint as an incidence of AKI defined as an increase in serum creatinine (sCr) of .5 mg/dL or 50% of baseline during vancomycin therapy. To evaluate the impact of each risk factor on the endpoint, we employed logistic regression analysis. The following factors were evaluated in this study: age, sex and high blood urea nitrogen (BUN)/sCrratio defined BUN/sCr of >20, high VCM trough defined as the max of VCM trough of >20 and combination use of piperacillin-tazobactam (PIPC/TAZ). Results: Fifty-eight patients were enrolled and analyzed in the present study. Median age was 46 (range 25 to 69) years old, and 32 patients were male. Among the study population, 37 patients had high BUN/sCr ratio, 13 patients had high VCM trough, and 13 patients received PIPC/TAZ. Regarding the incidence of the primary endpoint, there were 13 cases (22%) of AKI. In univariate analysis, high BUN/sCr ratio and
Table 1 #
Upfront Therapy
CRZ Duration (Months)
HLA
Conditioning
Follow-Up (Years)
Complications
GVHD
1 2 3 4 5
CHOP (8 cycles) ALCL-99 ALCL-99 NHL-BFM ALCL-99
22.5 2-3 7 3 3-4
MUD MRD MUD MRD MUD
Flu/alemtuzumab/600TBI Flu/ alemtuzumab/600TBI Flu/ alemtuzumab/600TBI Flu/ alemtuzumab/600TBI Cytarbine/cyclophos/alemtuzumab/1400TBI
3 3.3 3.5 3.6 1 month
Mixed Chimera (DLI x2) Mixed Chimera (DLI x4) None Mixed Chimera (DLI x 2) None
cGVHD None G1 aGVHD skin None None
S282
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
Table 1 Impact of Combination Drugs on Incidence of AKI Parameter
Age, per year Sex (Male) High BUN/sCr ratio High VCM trough Combination use of PIPC/TAZ
Univariate Analysis
Multivariate Analysis
HR(95%CI)
Pvalue
HR(95%CI)
Pvalue
.988 (.937-1.04) .417 (.117-1.48) 8.77 (1.05-73.3) 3.61 (.998-13.0) 3.96 (1.05-15.0)
.67 .18 .045 .05 .04
16.9 (1.36-209)
.03
6.73 (1.22-37.1)
.03
Results: Sixty-one patients were available for analysis: 16 in the myeloablative without r-ATG group, 16 in the myeloablative with r-ATG group, and 29 in the RIC control group. Only 14 patients in the group that utilized r-ATG as part of the conditioning regimen had mature 100-day data to utilize for analysis of the primary outcome. The incidence of CMV reactivation is increased with the use of r-ATG (25% vs. 43%). Data for 6-month and 12-month evaluation of incidence of GVHD is not yet mature, but a preliminary analysis shows a decrease in incidence of GVHD at 6 months (45% vs. 33%) and 12 months (44% vs. 20%), respectively, when r-ATG is utilized.
combination use of PIPC/TAZ was the significant factor of incidence of AKI (Table 1). Multivariate logistic regression analysis identified high BUN/sCr ratio and combination use of PIPC/TAZ as independently associated with the incidence of AKI (Table 1). Conclusion: Our study showed that high BUN/sCr and combination use of PIPC/TAZ were identified as risk factors of AKI in patients treated with VCM. Patients with these risk factors may require careful observation and avoid administration of PIPC/TAZ or consider to change the antibacterial drug.
386 Relationship of CMV Reactivation and Rabbit Antithymocyte Globulin Administration in Allogeneic Stem Cell Transplant Patients LeAnne Kennedy 1, Marie Cavalier 2, Dianna Howard 3. 1 Pharmacy, Wake Forest University Baptist Medical Center, Winston Salem, NC; 2 Pharmacy, Wake Forest Baptist Medical Center, Winston Salem, NC; 3 Hematology and Oncology, Wake Forest Comprehensive Cancer Center, Winston Salem, NC Background: Rabbit anti-thymocyte globulin (r-ATG) is widely used in the conditioning regimen before allogeneic stem cell transplant (SCT) in a number of disease settings, but largely in the context of unrelated donor or mismatched related donor transplants, to decrease the risk of graft-versus-host-disease (GVHD). Attempts to improve survival by the delivery of optimal therapy for the suppression of GVHD are thwarted by emergence of therapy-related infectious complications or primary disease relapse and offset any survival advantage. Cytomegalovirus (CMV) infections can be a significant factor in the post-transplant treatment related morbidity and mortality. R-ATG is associated with a delay in lymphocyte engraftment and prolonged time to absolute lymphocyte count (ALC) recovery, which has been implicated as a risk factor for CMV disease. Previously, only reduced intensity conditioning (RIC) matched unrelated donor (MUD) stem cell transplant recipients received GVHD prophylaxis with r-ATG. As of January 2015, both RIC MUD and fully myeloablative MUD transplants began receiving r-ATG as part of their conditioning regimen for GVHD prophylaxis. Objective: Determine if GVHD prophylaxis with r-ATG increased CMV reactivation 100 days post-transplant in patients who underwent a fully myeloablative MUD allogeneic stem cell transplant. The primary outcome will be the incidence of CMV at 100 days. Methods: This retrospective chart review evaluated patients who received a MUD allogeneic SCT from October 2012 to September 2016 at our institution. A group of RIC MUD patients will serve as a control, as these patients consistently received r-ATG for GVHD prophylaxis as part of their preparative regimen. To be included, patients received an allogeneic SCT from an unrelated donor for a hematologic malignancy and be at least 18 years of age.
Conclusions: Reactivation of CMV is increased when r-ATG is used as part of the conditioning regimen for GVHD prophylaxis. Mature data is still needed to determine the full benefit towards preventing GVHD.
387 Early Results of Phase II Study Using OMS721 in Patients with Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HCT-TMA) Samer K. Khaled 1, Yok Lam Kwong 2, Mark Smith 3, Ara Metjian 4, Steve Whitaker 5. 1 City of Hope, Duarte, CA; 2 Hong Kong University, Hong Kong, China; 3 Canterbury Health Laboratories, Christchurch, New Zealand; 4 Duke University School of Medicine, Durham, NC; 5 Omeros Corporation, Seattle, WA Introduction: TMA is a potentially life-threatening complication of HCT currently managed largely by amelioration of inciting factors including avoidance of calcineurininhibitors and treatment of ongoing infections, as well as supportive measures such as hemodialysis. Patients who do not respond have poor prognosis. Plasma exchange has not shown efficacy and no other therapy is approved. Complement activation has been reported in the pathogenesis of HCT-TMA. OMS721 is a human monoclonal IgG4 inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of complement activation. Here we report early results of OMS721 treatment in HCT-TMA patients. Methods: This is a Phase 2 uncontrolled, open-label, 3-stage study of OMS721 to assess safety, tolerability and clinical activity of OMS721 in patients with TMA (HCT-TMA, aHUS and TTP). Stage 1 included dose-escalation cohorts, Stage 2 expands disease-specific cohorts and Stage 3 provides optional extended treatment. For inclusion, patients with HCTTMA should demonstrate thrombocytopenia and evidence of microangiopathic hemolytic anemia, and at least 2 weeks must have elapsed since changes in immunosuppressive treatment. HCT-TMA patients received OMS721 X* mg/kg IV once weekly (Stage 1 up to 4 weeks and Stages 2 and 3 up to 8 * Dose is confidential.