The Outcome of Unrelated Hematopoietic Stem Cell Transplants with Total Body Irradiation (800 cGy) and Cyclophosphamide (120 mg/kg) in Adult Patients with Severe Aplastic Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3397-3397
Author(s):  
Jong Wook Lee ◽  
Byung Sik Cho ◽  
Yoo-Jin Kim ◽  
Hee Je Kim ◽  
Seok Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Total Body Irradiation ◽  
Cumulative Incidence ◽  
Disease Duration ◽  
Adult Patients ◽  
Platelet Recovery ◽  
Grade Ii ◽  
Total Body ◽  
Mismatched Donor ◽  
Grade Iii

Abstract Abstract 3397 Poster Board III-285 Backgrounds: We had reported the results of a pilot prospective study demonstrating the superiority of 800 cGy of total body irradiation (TBI) in combination with a 120 mg/kg of cyclophosphamide (CY) [TBI-800/CY-120] compared to the higher doses of TBI (1000 and 1200 cGy) as a conditioning regimen for unrelated stem cell transplantation (SCT) in adult patients with severe aplastic anemia (SAA) [Biology of Blood and Marrow Transplant 2007;13:836-870]. Patients and methods: To analyze the long-term results of unrelated SCT with TBI-800/CY-120 for adult SAA who failed to respond to immunosuppressive treatment, we prospectively enrolled 50 adult patients with SAA [median age, 28 years (range, 15-53)], including 26 patients of a previous pilot study. All patients received fractionated TBI (400 cGy/day) for 2 days followed by CY (60mg/kg/day, 2 days). Nine patients (18%) were very SAA. Enrolled patients had received multiple transfusions (median 64 units, range, 10-363) and long disease duration (median 48 months, range 2-323). High resolution DNA typing was done at HLA-A, -B, -C, -DR level. Seventeen patients (34%) received HLA-mismatched SCT at allele level. Thirty-eight patients (76%) received bone marrow and 12 (24%) peripheral blood stem cells (PBSC). All patients received tacrolimus and short-course of methotrexate as GVHD prophylaxis. Results: All patients achieved engraftment and the median day of neutrophil and platelet recovery was 13 days (range, 8-30) and 20 days (range, 9-200), respectively. There was one case of delayed platelet recovery, but platelet count rose slowly to the normal level thereafter. At a median follow-up of 38 months (range, 1-84), the estimated 3-year overall survival was 87.8%. The cumulative incidence of acute GVHD (aGVHD) over grade II (6/23, grade III and IV) and chronic GVHD (cGVHD) were 46.0% and 50.3% [limited (39%) vs. extensive (61%)], respectively. Among 7 patients who died, 4 patients and 1 patient died of severe aGVHD (grade III and IV) and cGVHD, respectively, 1 patient multi-organ failure, and 2 patient sepsis. Univariate analysis revealed the following risk factors: very SAA (P=0.018), HLA-mismatched donor at allele level (P=0.012), and older donor age (P=0.080) for aGVHD and previous aGVHD (P=0.030) and PBSC (P=0.024) for cGVHD. Multivariate analysis showed that only a HLA-mismatched donor at allele level (hazard ratio: 2.7, 95% CI: 1.2-6.2, P=0.018) was a significant factor associated with higher cumulative incidence of aGVHD over grade II. Conclusions: TBI-800/CY-120 conditioning resulted in excellent outcome of unrelated transplants in adult patients with SAA who had received multiple transfusions and long disease duration, which was comparable to those of matched sibling transplants. Additional strategies to prevent severe GVHD, for example, adding anti-thymocyte globulin, particularly for HLA-mismatched transplant and in case of PBSC as a stem cell source, will be helpful to improve the outcome in the future. Disclosures: No relevant conflicts of interest to declare.

Donor Type Impacts the Incidence of Severe Acute but Not Chronic Graft- Versus-Host Disease (GVHD) after Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplantation (ASCT) for Treatment of AML/MDS.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2227-2227
Author(s):  
Ri ma M. Saliba ◽  
Krishna V. Komanduri ◽  
Ebru Koca ◽  
Amin M. Alousi ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Donor Type ◽  
Grade Ii ◽  
Reduced Toxicity ◽  
Grade Iii

Abstract The use of reduced intensity conditioning has resulted in a significantly lower incidence of severe acute GVHD (aGVHD) compared with myeloablative conditioning. It is not known if reduced toxicity myeloablative conditioning has a similar impact. To answer this question, we evaluated the incidence of acute and chronic GVHD in a homogeneous group of AML/MDS patients treated with Fludarabine (Flu) and IV Busulfan (IVBu) between April 2001 and August 2005 at MD Anderson Cancer Center. METHODS: Retrospective analysis of all 195 consecutive AML/MDS patients (pts) who received conditioning with IVBu (130 mg/m2 for 4 days) and Flu (40 mg/m2 for 4 days) and allogeneic stem cell transplantation (ASCT). The cumulative incidence of GVHD was estimated considering disease progression or death in the absence of GVHD as competing risks. Cox’s proportional hazards regression analysis was used to compare the rates of GVHD. RESULTS: Median age at the time of transplantation was 46 years (12–65) with 4 pts being younger than 18 years. 45% of pts (n=93) were females and 47% (n=92) were in complete remission at the time of transplant. 55% (n=107) received a graft from a matched related donor (MRD), 38% (n=74) from a matched unrelated donor (MUD), and 7% (n=14) from a 1 Ag mismatched related or unrelated donor. Stem cell source was peripheral blood in 85% of recipients of a MRD graft and bone marrow in 88% of recipients of a MUD graft. The median number of CD34+ cells infused was 4.6 x 106/Kg (range 1.1–8.9) and 3.8 x106/Kg (range 0.2–13) in the two groups respectively. GVHD prophylaxis consisted of tacrolimus and mini-methotrexate. In addition, 29/74 recipients of a MUD graft received varying doses of pentostatin on a phase I/II clinical trial. Evaluation of GVHD was limited to pts who received a graft from a MRD or MUD and engrafted (n=179/181). With a median follow-up among survivors of 48 months (range 16–80), 100 day actuarial survival was similar in recipients of a MRD (96%) and MUD (93%) graft (p=0.3). A total of 50 pts (28%) developed grade II-IV and 15 pts (8%) grade III-IV aGVHD within 100 days after ASCT. Donor type was the most significant predictor of the incidence of grade II-IV aGVHD with a cumulative incidence of 18% (95% CI: 12–27) in recipients of a MRD graft and 38% (95% CI: 29–51) in recipients of a MUD graft (HR=0.4, p=0.001). Similarly the rate of grade III-IV aGVHD was significantly lower in recipients of a MRD graft (4% vs. 15%, HR=0.2, p=0.007). In contrast, donor type did not impact the incidence of chronic GVHD with a comparable cumulative incidence by 2 years in recipients of a MRD (53%, 95% CI: 44–63) and MUD graft (45%, 95% CI: 35–58), (HR=0.9, p=0.8). Similar results were observed when the comparison was restricted to de novo chronic GVHD (n=32). Use of peripheral blood stem cells was the only significant factor associated with a higher rate of chronic GVHD in recipients of a MRD graft (56% vs. 35%; HR=2.5, p=0.03). Female gender was associated with a significantly lower rate of chronic GVHD in recipients of a MUD graft (HR=0.4, p=0.006). There was no significant impact for age, percent donor chimerism at the time of engraftment, diagnosis (AML versus MDS), or donor/recipient CMV serostatus on the rate of grade II-IV aGVHD or chronic GVHD. CONCLUSION: The incidence of grade II-IV aGVHD is low following IVBuFlu conditioning and ASCT in AML/MDS patients. In this setting, donor type affects the incidence of acute but not chronic GVHD. Figure Figure

scholarly journals Effects of recombinant canine stem cell factor, a c-kit ligand, and recombinant granulocyte colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 20-26 ◽  
Author(s):  
FG Schuening ◽  
FR Appelbaum ◽  
HJ Deeg ◽  
M Sullivan-Pepe ◽  
TC Graham ◽  
...  
Keyword(s):  
Stem Cell ◽  
Total Body Irradiation ◽  
Stem Cell Factor ◽  
Combined Treatment ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Platelet Recovery ◽  
Hematopoietic Recovery ◽  
Total Body ◽  
Stimulating Factor

The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis were studied in normal dogs and in dogs given otherwise lethal total body irradiation (TBI) without marrow transplant. Results were compared with previous and concurrent data with recombinant granulocyte colony-stimulating factor (rG-CSF). Four normal dogs received 200 micrograms rcSCF per kilogram body weight daily either by continuous intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection in two divided doses for 20 days (n = 2). All dogs showed at least a twofold increase in peripheral blood neutrophil counts starting approximately 7 days after the initiation of treatment. Hematocrit level and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts were not elevated. Marrow sections after rcSCF treatment showed panhyperplasia. The only toxicity was facial edema during the first few days of rcSCF administration, presumably caused by mast cell stimulation. Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co sources. They were given no marrow infusion and received 200 micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2 hours of TBI. Five of the 10 dogs showed complete and sustained hematopoietic recovery and survived as compared with 1 of 28 control dogs not receiving growth factor (P < .005). RcSCF treatment allowed for hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar to those obtained with rG-CSF. The rate of neutrophil recovery in rcSCF-treated dogs after 400 cGy TBI was not different from that of rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster (P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and rcG-CSF after 500 cGy TBI did not result in strongly improved survival as compared with results obtained with either factor alone.

Impact of HLA Mismatch on the Incidence of Acute GVHD and Rejection after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation (RICT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2758-2758
Author(s):  
Takanori Teshima ◽  
K. Matsuo ◽  
K. Matsue ◽  
F. Kawano ◽  
S. Taniguchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Risk Factor ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Mismatched Donor

Abstract HLA incompatibility between the donor and recipient is the most critical factor governing the incidence of rejection and GVHD after conventional allogeneic stem cell transplantation. But the impact of HLA disparity on GVHD and graft rejection after RICT remains to be elucidated. We retrospectively analyzed the outcomes of 437 patients who underwent bone marrow (n=95) or peripheral blood stem cell RICT (n=342). The numbers of patients who received a graft from a HLA-matched (275 from siblings, 11 from family members, and 54 from unrelated donors), one-locus-mismatched, 2- or 3-loci-mismatched donor were 340, 65, and 32, respectively. The HLA-matched group included significantly higher population of patients who received cyclosporine alone for GVHD prophylaxis. The overall cumulative incidence of grade II-IV acute GVHD was 40% for all subjects. It was 38% (95% CI; 33%–43%) in recipients of HLA-matched donors, 43% (95% CI; 31%–54%) in those of one-locus-mismatched donors, and 54% (95% CI; 37%–68%) in those of 2–3-loci-mismatched donors. A Cox regression model adjusted for potential confounders including GVHD prophylaxis demonstrated that 2-3 loci-mismatch was identified as an independent risk factor of grade II-IV acute GVHD (Table). Use of antithymocyte globulin was identified as an independent better protective factor for GVHD (HR;0.66, p=.003). Cumulative incidence of rejection was significantly higher after one-locus mismatch RICT (Table) and the risk tended to increase in relation to an increase of HLA disparity. Malignant disease was identified as an independent prognostic factor for rejection. In patients with hematologic malignancies, overall survival (OS) of recipients of 2–3-loci-mismatched RICT at 1 year (38%, 95%CI; 21%–54%) was significantly worse than that after HLA-matched RICT (65%, 95%CI; 59%–70%). By contrast, there was no statistical difference in the incidence of grade II-IV acute GVHD and OS between HLA-matched RICT and one-locus-mismatched RICT. Multivariate analysis demonstrated 2–3-loci-mismatch (Table) and high-risk disease (HR; 2.3, p=.001) as independent risk factors for OS. Thus, HLA incompatibility between the donor and recipient is an important risk factor for rejection, acute GVHD and overall survival after RICT. Therefore RICT from a one-locus-mismatched donor may represent an effective alternative approach in patients lacking HLA-matched sibling donors. multivariate analysis n acute GVHD Rejection OS HR (95%CI) p HR (95%CI) p HR (95%CI) p match 340 1.0 1.0 1.0 1-mismatch 65 1.4 (0.9–2.2) 0.20 4.5 (1.1–17.9) 0.03 1.0 (0.6–1.6) 0.88 2–3-mismatch 32 2.2 (1.2–4.1) 0.02 7.0 (0.8–64.8) 0.08 3.3 (1.8–6.2) <0.001

Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Hematologic Malignancies: Outcomes Are Not Impaired in Patients of Advanced Age.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1208-1208
Author(s):  
John Koreth ◽  
Julie Aldridge ◽  
Haesook T. Kim ◽  
Edwin P. Alyea ◽  
Corey Cutler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Grade Ii

Abstract Abstract 1208 Poster Board I-230 The incidence of hematologic malignancies increases with age but by convention older patients have often been excluded from the curative approach intrinsic to allogeneic hematopoietic stem cell transplantation (HSCT). Limited information on reduced-intensity conditioning (RIC) HSCT outcomes in patients of advanced age restricts our ability to advocate this curative therapy for them, despite its lower toxicity compared to myeloablative HSCT. We report a retrospective analysis of 158 patients aged ≥60 yrs that underwent a consistent fludarabine/busulfan RIC HSCT for hematologic malignancies at DFCI between Jan 2002-Jun 2008. The median age was 63 yrs (range, 60-71). The principal diseases were myeloid in 70 % and lymphoid in 27%. 76% had high-risk disease (e.g., advanced stage or prior therapy). 12% had prior autologous transplants. Matched-unrelated, matched-related and mismatched adult donors were used in 56%, 34%, and 10% respectively. 96% received peripheral blood stem cell infusions. Graft-versus-host-disease (GVHD) prophylaxis included tacrolimus (91%) ± sirolimus (59%). The median follow-up among survivors was 34 months (range, 12.0-85.7). Median time to neutrophil and platelet recovery was 13 (range, 2-70) and 20 days (range, 11-78) respectively. Cumulative incidence of grade II-IV acute GHVD at 200 days was 19.6%, and chronic GVHD at 2 yrs was 45.9%. Cumulative incidence of relapse and non-relapse mortality (NRM) at 2 yrs was 57.1% and 10% respectively. Overall and progression-free survival (OS, PFS) at 2 years was 46% (95% CI, 38-54) and 35% (95% CI, 28-43) respectively. We compared outcomes in 110 patients aged 60-64 yrs (median 62 yrs) vs. 48 patients aged ≥65 yrs (median 67 yrs). The median follow-up among survivors was 35 (range, 12-85.7) and 32.4 months (range, 12.7-72.8) respectively. The groups did not differ significantly for covariates tested. Median time to neutrophil and platelet recovery was 13 (2-70) vs. 15 days (3-33), and 20 (11-78) vs. 19 days (12-60) respectively. Cumulative incidence of grade II-IV acute GHVD at 200 days was 18.2% vs. 22.9% (p=0.52), and of chronic GVHD at 2 yrs was 51.8% vs. 32.5% (p=0.01). Cumulative incidence of relapse and NRM at 2 yrs was 55.1% vs. 61.3% (p=0.31), and 10.5% vs. 8.3% (p=0.84) respectively. OS and PFS at 2 years was 49% (95% CI, 39-58) vs. 41% (95% CI, 26-54) (p=0.11) and 36% (95% CI, 27-45) vs. 35% (95% CI, 22-49) (p=0.24). In a multivariate Cox model disease-risk (high vs. low) was significantly associated with poorer PFS (HR 1.99, 95% CI 1.17-3.41, p=0.01) and OS (HR 1.80, 95% CI 1.03-3.17, p=0.04); and diagnosis (AML/MDS vs. other) was significantly associated with poorer PFS (HR 1.63, 95% CI 1.02-2.60, p=0.04). Age ≥65 yrs (vs. 60-64 yrs) was not associated with poorer PFS (HR 1.14, 95% CI 0.72-1.79, p=0.58) or OS (HR 1.32, 95% CI 0.83-2.11, p=0.24). In appropriately selected older patients RIC HSCT is well-tolerated with reasonable survival, in a cohort of patients with otherwise fatal illnesses. As in younger patients, relapse is the major cause of death. In patients aged ≥65 yrs, treatment-related toxicities are not increased and survival is comparable to those aged 60-64 yrs. RIC HSCT should not be excluded solely based on patient age. Novel strategies to reduce relapse post-HSCT should be prioritized. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effects of recombinant canine stem cell factor, a c-kit ligand, and recombinant granulocyte colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 20-26 ◽  
Author(s):  
FG Schuening ◽  
FR Appelbaum ◽  
HJ Deeg ◽  
M Sullivan-Pepe ◽  
TC Graham ◽  
...  
Keyword(s):  
Stem Cell ◽  
Total Body Irradiation ◽  
Stem Cell Factor ◽  
Combined Treatment ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Platelet Recovery ◽  
Hematopoietic Recovery ◽  
Total Body ◽  
Stimulating Factor

Abstract The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis were studied in normal dogs and in dogs given otherwise lethal total body irradiation (TBI) without marrow transplant. Results were compared with previous and concurrent data with recombinant granulocyte colony-stimulating factor (rG-CSF). Four normal dogs received 200 micrograms rcSCF per kilogram body weight daily either by continuous intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection in two divided doses for 20 days (n = 2). All dogs showed at least a twofold increase in peripheral blood neutrophil counts starting approximately 7 days after the initiation of treatment. Hematocrit level and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts were not elevated. Marrow sections after rcSCF treatment showed panhyperplasia. The only toxicity was facial edema during the first few days of rcSCF administration, presumably caused by mast cell stimulation. Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co sources. They were given no marrow infusion and received 200 micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2 hours of TBI. Five of the 10 dogs showed complete and sustained hematopoietic recovery and survived as compared with 1 of 28 control dogs not receiving growth factor (P < .005). RcSCF treatment allowed for hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar to those obtained with rG-CSF. The rate of neutrophil recovery in rcSCF-treated dogs after 400 cGy TBI was not different from that of rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster (P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and rcG-CSF after 500 cGy TBI did not result in strongly improved survival as compared with results obtained with either factor alone.

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