scholarly journals Comparison of Total Body Irradiation-Based with Intravenous Busulfan-Based Chemotherapy-Only Conditioning Regimens for Myeloablative Hematopoietic Cell Transplantation (HCT) in Adults with Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 679-679 ◽  
Author(s):  
Partow Kebriaei ◽  
Claudio Anasetti ◽  
Mei-Jie Zhang ◽  
Hai-Lin Wang ◽  
Ibrahim Aldoss ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Transplantation ◽  
Total Body Irradiation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Conditioning Regimens ◽  
Equity Ownership ◽  
Total Body

Abstract Total body irradiation (TBI)-based conditioning regimens are considered the standard of care for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic cell transplantation (HCT). However, due to concerns regarding acute and long-term toxicities, non-TBI regimens, commonly including busulfan (BU), have been increasingly explored. We performed a retrospective cohort analysis with the hypothesis that there would be equivalence of these two myeloablative approaches by reviewing outcomes for adult patients (pts), aged 18-60 years, undergoing a first, well-matched sibling, related or unrelated donor HCT in CR1 or CR2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2005-2014. Eight hundred nineteen pts received TBI (63% 9-12 Gy, 37% ≥13 Gy) combined with etoposide (25%) or cyclophosphamide (Cy) (75%) and 299 pts received intravenous BU combined with a second alkylator Cy (15%) or melphalan (Mel) (13%), or a nucleoside analogue fludarabine (Flu) (41%) or clofarabine (Clo)(30%). The majority of the BU-based pts were treated at the Moffitt or MD Anderson Cancer Center. The BU-based regimens were grouped together for analyses since no significant differences in basic outcomes among the different chemotherapy-only regimens were noted. Patients in the BU-containing group were older but had better performance status, took longer to achieve CR1 and longer to receive HCT; more received peripheral blood than marrow grafts, peri-HCT ATG, pre- and post HCT tyrosine kinase inhibitors ( TKI), and were treated more recently than pts in the TBI-based group (Table 1). With median follow-up of 3.6 years for the BU-based group and 5.3 years for the TBI-based group, adjusted 3 year outcomes showed treatment-related mortality (TRM) BU 19% vs. TBI 25% (p=.04); relapse BU 37% vs. TBI 28% (p=.007); disease-free survival (DFS) Bu 45% vs. TBI 48% (p=.35); and overall survival (OS) BU 57% vs. TBI 53% (p=.35) (Figures A-B). Patients in the BU group had significantly more grade II-IV acute GVHD (47% vs. 40%, p=.025), but marginally less chronic GVHD (49% vs. 55% at 3 years, p=.073). In multivariate analysis, the BU group had a significantly higher rate of acute GVHD after day 50 (RR 1.75, 95% CI 1.19-2.58, p=.004), but marginally less chronic GVHD (RR 0.83, 95% CI 0.68-1.01 p=.059) and higher risk of relapse (RR 1.46, 95% CI 1.15-1.85 p=.002) compared with TBI-based regimens. Despite the observed higher risks of acute GVHD and relapse, BU-based conditioning led to similar TRM, OS, and DFS following HCT for ALL. Table 1 Table 1. Figure Figure. Disclosures Ciurea: Spectrum Pharmaceuticals: Other: Advisory Board; Cyto-Sen Therapeutics: Equity Ownership. Seftel:Otsuka: Research Funding. Pulsipher:Medac: Other: Housing support for conference; Chimerix: Consultancy; Jazz Pharmaceutical: Consultancy; Novartis: Consultancy, Other: Study Steering Committee. Champlin:Ziopharm Oncology: Equity Ownership, Patents & Royalties; Intrexon: Equity Ownership, Patents & Royalties.

scholarly journals Comparative Effectiveness of Fludarabine and Busulfan Versus Fludarabine and 400 cGy Total Body Irradiation Reduced Intensity Conditioning Regimens for Allogeneic Hematopoietic Cell Transplantation for AML/MDS

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1920-1920
Author(s):  
Moaath Mustafa Ali ◽  
Donna M Abounader ◽  
Lisa A. Rybicki ◽  
Melissa A Yurch ◽  
Jamie Starn ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Total Body Irradiation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Reduced Intensity Conditioning ◽  
Post Transplant ◽  
Conditioning Regimens ◽  
Total Body ◽  
Reduced Intensity

Abstract Reduced intensity conditioning for allogeneic hematopoietic cell transplantation (alloHCT) has become a standard approach for older patients and for those with co-morbidities that prohibit myeloablative conditioning. The optimal conditioning regimen for patients with AML or MDS undergoing such transplants is not clear. Therefore we performed a single center, retrospective analysis comparing busulfan (100 mg/m2/day on days -5, -4, -3, -2) and fludarabine (40 mg/m2/day on days -5, -4, -3, -2) (BuFlu) versus fludarabine (30 m2/day on days -5, -4, -3) and 400 cGy total body irradiation (200 cGy on days -1 and 0) (FluTBI) conditioning. All of the BuFlu transplants were performed as inpatient hospitalizations while all of those with FluTBI were performed as an outpatient. A total of 71 patients in two cohorts were included. The first study cohort consisted of 38 patients (23 AML, 15 MDS) who received FluTBI from 3/2004-4/2010, and the second included 33 (20 AML, 13 MDS) patients conditioned with FluBu from 6/2010-12/2013. The groups had similar disease risk and HCT comorbidity index scores. The BuFlu patients were older (median age 65 [range, 34-73] vs. 61[range, 44-70] years, P=0.03), but there were no other differences in patient or disease characteristics. All patients received peripheral blood stem cells as the graft source. The donor sources were 53% matched related (MRD) and 47% matched unrelated (MUD) for FluTBI patients and 58% MRD and 42% MUD for BuFlu patients. The BuFlu group received more red blood cell (RBC) transfusions (median 4 vs. 2, P=0.02), but there were no differences in platelet transfusion requirements. Platelet recovery was longer for patients receiving BuFlu than FluTBI (median 16 vs. 12 days, P=0.004), but there was no difference in cumulative incidence of neutrophil recovery. The respective median number of days hospitalized in the first 100 days post-transplant was 22 vs. 10 days (P<0.001) and in the first year was 40 vs. 16 days (P<0.001). Post-transplant outcomes are shown in the Table. The most common causes of death were relapse and infection for both the FluTBI (44% and 13%) and BuFlu (57% and 14%) groups. Quality of life assessments using the FACT-BMT were performed pre-alloHCT, at day 100, 6 months and 1 year. There was no difference in physical, social, emotional, and functional well-beings, additional concerns, trial outcome index or total score between the two groups at baseline or any of the follow-up timepoints. We conclude that alloHCT using FluTBI or BuFlu reduced intensity conditioning regimens results in comparable outcomes in patients with AML/MDS. The greater RBC transfusion requirement and need for inpatient hospitalization with the BuFlu regimen have implications for healthcare resource utilization. Future prospective investigation comparing these regimens with larger patient cohorts and cost-effectiveness analyses are warranted. Table 1. Patient outcomes Variable FluTBI N (%) BuFlu N (%) P-value T-cell complete donor chimerism 29 (78) 26 (81) 0.83 Graft failure/rejection 3 (8) 3 (9) 0.87 Grade II-IV acute GvHD 13 (34) 17 (52) 0.24 Grade III-IV acute GvHD 3 (8) 6 (18) 0.21 Any Chronic GvHD 16 (42) 14 (42) 0.91 Extensive chronic GvHD 8 (21) 13 (39) 0.06 CMV reactivation 12 (32) 13 (39) 0.66 Fungal Infection 2 (5) 1 (3) 0.83 Relapse (2-years) 20 (53) 17 (52) 0.96 100 day mortality 13 (95% CI 6-29 ) 9 (95% CI 3-26 ) 0.59 Non-relapse mortality (2-years) 29 (95% CI 15-44) 29 (95% CI 14-45) 0.56 Relapse mortality (2-years) 34 (95% CI 20-49) 36 (95% CI 20-53) 0.86 Overall survival (2-years) 37 (95% CI 22-52) 35 (95% CI 19-51) 0.73 Disclosures Majhail: Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

scholarly journals Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 903-909 ◽  
Author(s):  
Ginna G. Laport ◽  
Joseph C. Alvarnas ◽  
Joycelynne M. Palmer ◽  
David S. Snyder ◽  
Marilyn L. Slovak ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Total Body Irradiation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Status ◽  
Matched Sibling ◽  
Total Body

Abstract Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 × 109/L vs > 30 × 109/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph+ ALL patients and that disease status at the time of HCT is an important predictor of outcome.

Salvage Allogeneic Hematopoietic Cell Transplantation with Fludarabine and Total Body Irradiation (3 or 4 Gy) after Failure of First Allografts.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3272-3272
Author(s):  
Boglarka Gyurkocza ◽  
Thai M. Cao ◽  
Rainer F. Storb ◽  
Thoralf Lange ◽  
Wendy Leisenring ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Umbilical Cord ◽  
Total Body Irradiation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Idiopathic Myelofibrosis ◽  
Total Body

Abstract We analyzed data from 38 patients (median age = 56, range: 8 – 68 years) with acute leukemia (n=15), chronic idiopathic myelofibrosis (n=6), myelodysplastic syndrome with or without myeloproliferative disorder (n=5), chronic myeloid leukemia (n=4), non- Hodgkin lymphoma (n=4), aplastic anemia (n=2), multiple myeloma (n=1) and renal cell carcinoma (n=1), who underwent salvage allogeneic hematopoietic cell transplantation (HCT) for allograft failure. In 14 cases the original donors were used for second HCT, while in 24 cases different donors were identified (Table 1). Conditioning regimens for first HCTs included total body irradiation (TBI; 2 Gy) with or without fludarabine (Flu; n=28), myeloablative regimens (busulfan-cyclophosphamide, n=6; cyclophosphamide-TBI, n=2); and other, cyclophosphamide-anti-thymocyte globulin-based regimens (n=3). Conditioning for salvage HCT consisted of Flu 30 mg/m2/day on days -4 to -2 followed by TBI of 3 (n=24) or 4 (n=14) Gy on day 0. Cyclosporine and mycophenolate mofetil were used for postgrafting immunosuppression. The median time between first and salvage HCTs was 91 (range, 29 to 1004) days. Sustained second grafts were achieved in 34 patients (89%), while grafts failed in 4 patients (11%), all of whom had idiopathic myelofibrosis. With a median follow-up among surviving patients of 2.0 (range, 0.3 to 7.8) years, the 2 and 4 year Kaplan-Meier survival estimates were 49% (95% CI: 31%, 66%) and 42% (95% CI: 23%, 61%), respectively. The 2 year relapse-rate and non-relapse mortality were 36% (95% CI: 20%, 52%) and 25% (95% CI: 11%, 41%), respectively. The cumulative incidences of grades 2–4 acute and moderate-severe chronic graft-versus-host disease (GVHD) at 2 years were 42% and 41%, respectively. Four patients with chronic GVHD discontinued systemic immunosuppressive therapy at a median of 2.5 years. Within the limitations of the small patient numbers studied, TBI dose (3 vs. 4 Gy), same vs. different donors for salvage HCT, donor type (related, unrelated, HLA-haploidentical related vs. double umbilical cord), and HCT comorbidity scores did not appear to affect outcomes. Based on this retrospective multicenter analysis, we conclude that graft failure following allogeneic HCT can be effectively overcome by second transplantation using conditioning with Flu and low dose TBI (3 or 4 Gy), which should be further investigated in a prospective manner. Table 1. Donors in 1st and 2nd HCTs. HLA-MURD: HLA-matched unrelated donor; HLA-MMURD: HLA-mismatched unrelated donor, UCB: umbilical cord blood. 2nd HCT Different Donor 1st HCT Same Donor HLA-MURD HLA-MMURD Double UCB HLA-haploidentical HLA-identical sibling 11 11 - - - - HLA-MURD 17 3 10 4 - - HLA-MMURD 8 - 1 7 - - Double UCB 2 - - - 1 1

Long-Term Outcomes after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5534-5534
Author(s):  
Moaath Mustafa Ali ◽  
Donna M Abounader ◽  
Lisa A. Rybicki ◽  
Jamie Starn ◽  
Christina Ferraro ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Long Term Outcomes ◽  
Post Transplant

Abstract Allogeneic hematopoietic cell transplantation (alloHCT) is a curative therapy for high-risk acute lymphoblastic leukemia (ALL). However, long-term outcomes after alloHCT for adult ALL have not been well described. We conducted a retrospective cohort study of 72 consecutive adult ALL patients who underwent a first myeloablative alloHCT at our institution from January 2000-December 2013. Median age at HCT was 38 yrs (range, 18-62), 40 (56%) were male, 18 (38%) had high HCT CI score, 14 (19%) had prior CNS leukemia and 35 (49%) had BCR-ABL+ disease. Donor source was HLA-matched related donor for 50% patients and 90% received PBSC as graft source. All patients were transplanted in CR (72% were in 1st or 2nd CR) and 92% received T-cell replete grafts. Median time from diagnosis to alloHCT was 5 months (range, 2-90). The incidences of grade II-IV and III-IV acute GvHD, chronic GvHD and extensive chronic GvHD were 43%, 13%, 51% and 36%, respectively. The median follow-up for our cohort is 76 months. At 6 years after HCT, probability of overall survival (OS) was 33% (95% CI, 21-44%) and relapse-free survival (RFS) was 30% (95% CI, 19-42%), and the cumulative incidence of relapse was 36% (95% CI, 25-48%) and non-relapse mortality (NRM) was 37% (95% CI, 26-49%). The most common causes of death were relapse (43%) and infection (21%); majority of relapses occurred within the first 2-years post-transplantation. There were no second cancer related deaths. In multivariable analyses, factors significantly associated with OS were HCT CI score (HR 2.69 for high vs. low/int., P=0.002) and CMV status (HR 2.62 for donor+ vs. others, P=0.05). HCT CI score was the only predictive factor for RFS (HR 2.26 for high, P=0.007). We also compared outcomes by BCR-ABL status. BCR-ABL+ patients were older (median age 42 vs. 36 yrs, p=0.02), had low HCT CI score (34% vs 22%, p=0.01), were more likely to be in CR1 (74% vs. 32%, p=0.002), and as a result, proceeded to HCT sooner after diagnosis (median 4 vs 7 months, p=<0.001). For BCR-ABL+ and BCR-ABL- patients, 6 year OS was 41% and 25%, RFS was 40% and 21%, relapse was 27% and 45% and NRM was 38% and 36% (P=NS for all comparisons). Myeloablative alloHCT can provide long-term survival for selected high-risk adult ALL patients. Relapses are relatively uncommon after 2 years post-transplant. Long-term NRM is high in this population and we did not observe a plateau in its incidence until 7.5 years post-transplant, suggesting the need for long-term follow up to prevent and manage late complications of alloHCT. Figure 1. Figure 1. Disclosures Majhail: Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

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