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Comparison of Reduced-Intensity Conditioning Regimens Used in Patients Undergoing Hematopoietic Stem Cell Transplantation for Myelofibrosis
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Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
Figure 1. Comparison of known risk factors.
EBV reactivation was 34 days (range, 13-602) from HCT. Level of EBV copies/ml at the time of initiation of pre-R was 2000-3999 in 14 (23%), 4000-5999 in 11 (18%), 6000-7999 in 3 (5%) and ≥ 8000 in 32 (53%). Median of highest level of EBV load was 10,300 copies/ml (range, 2000-645,000). Doses required to clear viremia were 1 in 31 (53%), 2 in 15 (26%), 3 in 5 (9%) and 4 in 7 (12%) pts. It took a median of 9 days (range, 1-41) from the initiation of pre-R to resolve viremia. No unexpected toxicities were reported from the use of pre-R. On a median follow-up of 22.7 months after HCT, no pts died due to EBV reactivation or rituximab use. Pts who developed PTLD (N = 7): Of the 7 pts who developed EBV related PTLD, one had pre-R treatment prior to developing PTLD. This pt was diagnosed with PTLD 146 days after pre-R treatment. The other 6 had not received pre-R therapy. Known risk factors for PTLD development were compared between the 2 groups and shown in Figure 1. Conclusions: Despite low numbers, this study exhibits compelling evidence that pre-R can be given to prevent PTLD in patients with EBV reactivation post-HCT. Further studies in a prospective fashion are required to further determine the EBV load at which treatment should begin.
383 Comparison of Reduced-Intensity Conditioning Regimens Used in Patients Undergoing Hematopoietic Stem Cell Transplantation for Myelofibrosis Tania Jain 1, M’hamed Temkit 2, Daniel K. Partain 3, Mrinal S. Patnaik 4, James L. Slack 1, Nandita Khera 1, William J. Hogan 5, Vivek Roy 6, Pierre Noel 1, Jose Leis 1, Lisa Z. Sproat 1, Veena Fauble 7, Ruben A. Mesa 1, Jeanne Palmer 1. 1 Mayo Clinic Cancer Center, Phoenix, AZ; 2 Division of Health Sciences Research, Mayo Clinic, Scottsdale, AZ; 3 Internal Medicine, Mayo Clinic, Rochester, MN; 4 Division of Hematology, Mayo Clinic, Rochester, MN; 5 Hematology and Bone Marrow Transplant, Mayo Clinic, Rochester, MN; 6 Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL; 7 BMT, Banner/MD Anderson Blood & Marrow Transplant Program, Phoenix, AZ Background: Reduced intensity conditioning (RIC) regimens are used for hematopoietic stem cell transplantation
(HSCT) in patients with myelofibrosis due to age and/or comorbidities. The various RIC regimens used at our institute are fludarabine-busulphan (FBu), fludarabine-melphalan (FM) and fludarabine carmustine melphalan (FBM). Comparison between the 3 groups has not yet been well described in a setting of myelofibrosis. Methods: This is a retrospective study of patients undergoing HSCT for myelofibrosis at Mayo Clinic in Minnesota, Florida and Arizona between January 2006 and December 2015. Comparison in chimerism studies at day +30 and day +100, graft versus host disease (GVHD) and survival was made amongst patients who received the 3 different RIC regimens. Standard statistical methods and tests were used to compare continuous and categorical variables; while Kaplan-Meier method and the Log-rank test were used to provide and compare the survival curves. Results: A total of 55 patients who underwent HSCT received one of the above RIC regimens whose chimerism, disease relapse and survival data was available: 15 received FBu, 18 received FM and 22 received FBM. Median age at diagnosis was 60 years, 56.5 years and 56 years (P = .11) and median age at HSCT was 63 years, 58 years and 59 years (P = .19) in FBu, FM and FBM groups, respectively. Thymoglobulin was used with conditioning in 10 (67%), 6 (33%) and 21 (95%) patients in FBu, FM and FBM, respectively. Donor source was matched related in 5 (33%), 10 (56%), 11 (50%); matched unrelated in 10 (67%), 6 (33%), 8 (36%); mismatched unrelated in 0, 2 (11%), 2 (9%) in FBu, FM and FBM, respectively. JAK2V617F mutation was positive in 10 (67%), 14 (78%), 11 (50%) patients in the FBu, FM and FBM groups, respectively (P = .09). Chimerism studies: At day +30, CD3 was a 100% donor in 2 (14.3%), 8 (88.9%) and 19 (86.4%) patients (P < .0001) and CD33 was a 100% donor in 11 (73.3%), 16 (94.1%) and 22 (100%) patients (P = .02) in FBu, FM and FBM groups, respectively. At day +100, CD3 was a 100% donor in 2 (15.4%), 7 (77.8%) and 16 (88.9%) patients (P = .0001) and CD33 was 100% donor in 8 (61.5%), 9 (90%) and 18 (100%) patients (P = .01) in FBu, FM and FBM groups, respectively. Graft versus host disease: Acute GVHD was seen in 7 (46.7%), 16 (88.9%) and 18 (81.8%) patients (P = .01) while chronic GVHD was seen in 7 (46.7%), 12 (66.7%) and 8 (40%) patients (P = .24) in FBu, FM and FBM groups, respectively.
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
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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
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
Figure 1. Comparison of known risk factors.
EBV reactivation was 34 days (range, 13-602) from HCT. Level of EBV copies/ml at the time of initiation of pre-R was 2000-3999 in 14 (23%), 4000-5999 in 11 (18%), 6000-7999 in 3 (5%) and ≥ 8000 in 32 (53%). Median of highest level of EBV load was 10,300 copies/ml (range, 2000-645,000). Doses required to clear viremia were 1 in 31 (53%), 2 in 15 (26%), 3 in 5 (9%) and 4 in 7 (12%) pts. It took a median of 9 days (range, 1-41) from the initiation of pre-R to resolve viremia. No unexpected toxicities were reported from the use of pre-R. On a median follow-up of 22.7 months after HCT, no pts died due to EBV reactivation or rituximab use. Pts who developed PTLD (N = 7): Of the 7 pts who developed EBV related PTLD, one had pre-R treatment prior to developing PTLD. This pt was diagnosed with PTLD 146 days after pre-R treatment. The other 6 had not received pre-R therapy. Known risk factors for PTLD development were compared between the 2 groups and shown in Figure 1. Conclusions: Despite low numbers, this study exhibits compelling evidence that pre-R can be given to prevent PTLD in patients with EBV reactivation post-HCT. Further studies in a prospective fashion are required to further determine the EBV load at which treatment should begin.
383 Comparison of Reduced-Intensity Conditioning Regimens Used in Patients Undergoing Hematopoietic Stem Cell Transplantation for Myelofibrosis Tania Jain 1, M’hamed Temkit 2, Daniel K. Partain 3, Mrinal S. Patnaik 4, James L. Slack 1, Nandita Khera 1, William J. Hogan 5, Vivek Roy 6, Pierre Noel 1, Jose Leis 1, Lisa Z. Sproat 1, Veena Fauble 7, Ruben A. Mesa 1, Jeanne Palmer 1. 1 Mayo Clinic Cancer Center, Phoenix, AZ; 2 Division of Health Sciences Research, Mayo Clinic, Scottsdale, AZ; 3 Internal Medicine, Mayo Clinic, Rochester, MN; 4 Division of Hematology, Mayo Clinic, Rochester, MN; 5 Hematology and Bone Marrow Transplant, Mayo Clinic, Rochester, MN; 6 Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL; 7 BMT, Banner/MD Anderson Blood & Marrow Transplant Program, Phoenix, AZ Background: Reduced intensity conditioning (RIC) regimens are used for hematopoietic stem cell transplantation
(HSCT) in patients with myelofibrosis due to age and/or comorbidities. The various RIC regimens used at our institute are fludarabine-busulphan (FBu), fludarabine-melphalan (FM) and fludarabine carmustine melphalan (FBM). Comparison between the 3 groups has not yet been well described in a setting of myelofibrosis. Methods: This is a retrospective study of patients undergoing HSCT for myelofibrosis at Mayo Clinic in Minnesota, Florida and Arizona between January 2006 and December 2015. Comparison in chimerism studies at day +30 and day +100, graft versus host disease (GVHD) and survival was made amongst patients who received the 3 different RIC regimens. Standard statistical methods and tests were used to compare continuous and categorical variables; while Kaplan-Meier method and the Log-rank test were used to provide and compare the survival curves. Results: A total of 55 patients who underwent HSCT received one of the above RIC regimens whose chimerism, disease relapse and survival data was available: 15 received FBu, 18 received FM and 22 received FBM. Median age at diagnosis was 60 years, 56.5 years and 56 years (P = .11) and median age at HSCT was 63 years, 58 years and 59 years (P = .19) in FBu, FM and FBM groups, respectively. Thymoglobulin was used with conditioning in 10 (67%), 6 (33%) and 21 (95%) patients in FBu, FM and FBM, respectively. Donor source was matched related in 5 (33%), 10 (56%), 11 (50%); matched unrelated in 10 (67%), 6 (33%), 8 (36%); mismatched unrelated in 0, 2 (11%), 2 (9%) in FBu, FM and FBM, respectively. JAK2V617F mutation was positive in 10 (67%), 14 (78%), 11 (50%) patients in the FBu, FM and FBM groups, respectively (P = .09). Chimerism studies: At day +30, CD3 was a 100% donor in 2 (14.3%), 8 (88.9%) and 19 (86.4%) patients (P < .0001) and CD33 was a 100% donor in 11 (73.3%), 16 (94.1%) and 22 (100%) patients (P = .02) in FBu, FM and FBM groups, respectively. At day +100, CD3 was a 100% donor in 2 (15.4%), 7 (77.8%) and 16 (88.9%) patients (P = .0001) and CD33 was 100% donor in 8 (61.5%), 9 (90%) and 18 (100%) patients (P = .01) in FBu, FM and FBM groups, respectively. Graft versus host disease: Acute GVHD was seen in 7 (46.7%), 16 (88.9%) and 18 (81.8%) patients (P = .01) while chronic GVHD was seen in 7 (46.7%), 12 (66.7%) and 8 (40%) patients (P = .24) in FBu, FM and FBM groups, respectively.
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
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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