Amelioration of Late Complications Following Unrelated Donor Bone Marrow Transplantation When Anti-Thymocyte Globulin Is Used as a Part of Conditioning.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5319-5319
Author(s):  
Matthew E. Adess ◽  
Patrick Stiff ◽  
Tulio Rodriguez ◽  
John Norton ◽  
Mala Parthasarthy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Graft Rejection ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Donor Bone Marrow ◽  
Number Of Patients ◽  
Significant Difference ◽  
Unrelated Donors ◽  
The Impact

Abstract Polyclonal anti-thymocyte globulin (ATG) reduces the risk for primary graft rejection as well as acute graft-versus-host disease (GVHD) by depleting T cells in both the host and the infused allograft. However, the impact of ATG on late outcomes is less certain. We report the results of a retrospective landmark analysis of consecutive patients who underwent an unrelated donor bone marrow transplant at our center between January 2001 and October 2005 (n=45) and survived at least 90 days following transplant. We compared late outcomes in patients who either recieved ATG (n=25) or did not (n=20) as a part of their conditioning regimen. Conditioning was with either busulfan and cyclophosphamide (n= 28; 17 without ATG) or BCNU, etoposide, cytarabine, and melphalan (n=18; 3 without ATG). Most patients (20) received rabbit ATG at a median dose of 3 mg/kg (range: 1.5–9 mg/kg) on day -4 and -3. Others were given equine ATG. GVHD prophylaxis consisted of tacrolimus + methotrexate in both groups. Median age was 42 years (range 18–65; 14 female). Bone marrow from unrelated donors matched at HLA-A, B, C, and DRB1 (7/8 and 8/8 matches) was used as the stem cell source. Diseases treated were CML (11), HD (9), AML (8), MDS (6), NHL (3), MM (3), and other (5). A median of 3 prior therapies had been given before transplant (range 1–5). There was no significant difference (Pearson χ2) in the number of patients beyond CR1/CP1 (n=25) and those having failed a prior autograft (n=17) between the two groups. The median overall survival in the recipients of ATG was 1382 days (95% CI: 373– 2391 days) as opposed to 364 days (95% CI: 0–851) in those not receiving ATG (P=0.125 by Log-Rank test); with a 1-year overall survival of 76% (59%–93%) vs. 50% (28–72) in the ATG vs. no ATG cohorts respectively, and 69% (49–89) vs. 44% (22–66) at 2-years. The 1-year progression free survival was 84% (69–98) vs.90% (77–100) in the ATG vs. no ATG cohorts, and 84% (69–98) vs. 67% (37–97) at 2 years. Chronic GVHD developed in 15/20 (75%) patients not receiving ATG (45% extensive), and in 12/25 (48%) in those recieving ATG (16% extensive) (P=0.06 Pearson χ2). Graft rejection was seen in 2/20 patients in the non-ATG arm and 1/25 patients in the ATG arm. Despite a lower incidence of chronic GVHD, the relapse rate was similar in the two groups (16% in the ATG group vs. 20% in the non-ATG group; P=0.73). Lymphoid recovery was similar in the two groups. The absolute lymphocyte counts at day-90 and day-180 post transplant were 680 vs 800/microL and 1100 vs. 1500/microL in the no ATG vs. ATG cohorts (P=0.275 repeated measures ANOVA). Serious late infections requiring parenteral antimicrobial treatment occured in 8 patients (32%) receiving ATG, and in 9 patients (45%) in the non-ATG arm ((P=0.248). CMV reactivation was seen in 8 patients (32%) receiving ATG, and 7 (35%) in the non-ATG arm. Eleven patients (55%) have died in the no ATG cohort from either relapse (2), GVHD (4) or infection (5); whereas in the ATG cohort 9 (36%) have died of either relapse (4), GVHD (3) or infection (2). In conclusion, ATG appears to reduce delayed transplant related complications, such as chronic GVHD and infections, in patients receiving bone marrow from unrelated donors. This may lead to a favorable trend towards improved survival in patients recieving ATG as a part of non-total body irradiation based conditioning.

Improved Outcome After Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation (RI-HCT) for Myelodysplastic Syndrome (MDS) Using Tacrolimus/Sirolimus-Based Gvhd Prophylaxis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2771-2771 ◽  
Author(s):  
Ryotaro Nakamura ◽  
Joycelynne Palmer ◽  
Pablo Parker ◽  
Anthony Stein ◽  
Tracey Stiller ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Significant Difference ◽  
One Year ◽  
The Impact ◽  
Bone Marrow Blasts ◽  
Improved Outcome

Abstract Abstract 2771 Poster Board II-747 We previously reported an encouraging result with RI-HCT for MDS (Bone Marrow Transplant 2007; 40:843-50) using flugarabine/melphalan conditioning and cyclosporine (CSA)/mycophenolate (MMF) as GVHD prophylaxis. In order to further improve upon the outcome in the RI-HCT setting, we initiated a series of clinical trials at City of Hope National Medical Center designed to evaluate the impact of tacrolimus (FK)/sirolimus (SIRO)-based GVHD prophylaxis. Here we report the combined, updated results from a consecutive case-series of 89 patients with MDS (including AML progressed from MDS) who underwent RI-HCT from 2000 to 2008 and received either CSA/MMF (n =44) or FK/SIRO (n=45)-based GVHD prophylaxis. All patients received fludarabine 125 mg/m2 plus melphalan 140 mg/m2 followed by an allogeneic HCT (peripheral blood: n=83, bone marrow: n=6) from an HLA-identical sibling (SIB: n=35) or unrelated donor (MUD: n=54). Additional ATG was given to 12 patients. For MUD transplants a short course of methotrexate was added to CSA/MMF or FK/SIRO. The median age was 59 years (range: 20-71) and 31 (35%) patients were female, 58 (65%) were male. Diagnoses at transplant were RA (n=21), RARS (n=1), RAEB/RAEBT (n=36), and AML from prior MDS (n=31). Cytogenetic risk was low in 15 (17%), intermediate in 37 (41.5%), high in 37 (41.5%) patients. By IPSS criteria (for MDS only), 2 patients had low, 24 had int-1, 20 had int-2, and 12 had high-risk MDS. Twenty-seven patients had therapy-related MDS including 14 with prior autologous HCT. The median follow-up time for surviving patients was 39 months (range: 24-68) for the CSA/MMF group and 17 months (range: 4-39) for the FK/SIRO group. All but two patients (1 in CSA/MMF, 1 in FK/SIRO) engrafted with the median neutrophil recovery at 15 days (range: 11-55). The baseline patient, disease and transplant characteristics were similar between CSA/MMF and FK/SIRO, except for an increased percentage of therap-related MDS in the CSA/MMF group (43% vs. 18%, p<0.01). The median donor chimerism by STR at day 30 post-transplant was 100% in both groups (p=0.6). FK/SIRO was associated with a significantly reduced one-year non-relapse mortality (NRM) (11.4%) compared with CSA/MMF (36.2%, p=0.01). This improvement in NRM translated into a trend for improved overall survival (81.4% vs. 52.3%, p=0.1) and disease-free survival (72.2% vs. 52.3%, p=0.08) at one year. While we observed no significant difference in acute GVHD grade II-IV between CSA/MMF and FK/SIRO, FK/SIRO was associated with a significant reduction in grade IV GVHD (0% versus 26%, p<0.01) and a trend for III-IV GVHD (31% vs. 55%, p=0.1). There was no significant difference in chronic GVHD between FK/SIRO (60%) and CSA/MMF (56%, p=0.8). In multivariate analysis, the use of FK/SIRO was independently associated with improved NRM after adjusted for donor type, therapy-related MDS, %bone marrow blasts, and HLA match status (Table). In conclusion, FK/SIRO-based GVHD prophylaxis was associated with an improved outcome after RI-HCT for MDS attributable to the reduced risk for severe acute GVHD.Variables for NRMHazard Ratio (95% CI)p-valueDe novo (n=62) Therapy-related (n=27)baseline 0.75 (0.31–1.89)0.55Sibling donor (n=35) Unrelated donor (n=54)baseline 2.17 (0.70–6.74)0.18Bone marrow blasts < or =10% (n=67) Bone marrow blasts >10% (n=22)baseline 2.13 (0.92–4.96)0.08HLA match (sibling donor or 10/10 MUD, n=72)HLA < mismatch MUD (<10/10 match, n=17)baseline 6.26 (2.11–18.55)0.001FK/SIRO (n=45) CSA/MMF (n=44)baseline 6.58 (2.15–20.14)0.001 Disclosures: Off Label Use: cyclosporine, cellcept, tacrolimus, sirolimus, and methotrexate for GVHD prophylaxis.

scholarly journals Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2354-2363 ◽  
Author(s):  
J Casper ◽  
B Camitta ◽  
R Truitt ◽  
LA Baxter-Lowe ◽  
N Bunin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Allogeneic Bone Marrow Transplantation ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Allogeneic Bone ◽  
Significant Difference ◽  
Matched Sibling

Allogeneic bone marrow transplantation is the treatment of choice for many childhood leukemias. The donor of choice-an HLA matched sibling-is only available about 30% of the time. Unrelated donors are an alternative choice. In this report, we describe the results of unrelated donor bone marrow transplants (BMT) in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10 chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13 patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6 of these were reactive in mixed lymphocyte culture. The other 37 patients were mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant conditioning included cytosine arabinoside, cyclophosphamide, fractionated total body irradiation (TBI) (with lung, liver, and more recently, kidney shielding), and methylprednisolone. High-risk patients also received busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of T- cell depletion with IgM monoclonal antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine patients (98%) engrafted. Median times to greater than 500 polymorphonuclear leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20 days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13 (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7% (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients with low-risk disease (ALL or AML in first or second remission and CML in chronic phase) had a better EFS than children with high-risk disease (60% v 34%, P = .07). There was no significant difference in EFS between patients who were serologically matched with their donors (46%) and those who were partially mismatched (43%) (P = .97). These data compare favorably with published reports for children transplanted with HLA-matched sibling donors and should encourage earlier consideration of unrelated donor BMT in children with leukemia or myelodysplasia.

scholarly journals Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia

Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 2256-2262 ◽  
Author(s):  
John E. Wagner ◽  
Mary Eapen ◽  
Margaret L. MacMillan ◽  
Richard E. Harris ◽  
Ricardo Pasquini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Fanconi Anemia ◽  
Marrow Transplantation ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Donor Bone Marrow ◽  
The Impact

AbstractBone marrow transplantation (BMT) is the only known cure for the hematologic manifestations of Fanconi anemia (FA). Potential benefits of unrelated donor BMT for FA, however, have been severely limited by graft rejection and treatment-related mortality with resultant poor survival. Therefore, we evaluated the impact of potential prognostic factors on hematopoietic recovery, graft-versus-host disease (GVHD), and mortality in 98 recipients of unrelated donor BMT who received transplants between 1990 and 2003. Probabilities of neutrophil (89% vs 69%; P = .02) and platelet (74% vs 23%; P < .001) recovery were higher after fludarabine-containing regimens than nonfludarabine-containing regimens. Risks of acute GVHD (relative risk [RR], 4.29; P < .001) were higher with non–T-cell–depleted grafts. The day-100 mortality rate was significantly higher after nonfludarabine-containing regimens than fludarabine-containing regimens (65% vs 24%, respectively; P < .001). Corresponding 3-year adjusted overall survival rates were 13% versus 52% (P < .001). In addition, mortality was higher in recipients who were older (> 10 years), who were cytomegalovirus (CMV) seropositive, and who received more than 20 blood product transfusions before BMT. Based on these results, significant practice changes are suggested: use of a fludarabine-containing conditioning regimen in the context of T-cell–depleted marrow allografts, and earlier referral for transplantation prior to excessive transfusions in patients with marrow failure.

No Improvement of Overall-Survival in Children with High-Risk Acute Myeloid Leukemia by Stem Cell Transplantation in 1st Complete Remission.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 320-320 ◽  
Author(s):  
Dirk Reinhardt ◽  
Bernhard Kremens ◽  
Martin Zimmermann ◽  
Josef Vormoor ◽  
Michael Dworzak ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Children And Adolescents ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Hla Typing ◽  
Unrelated Donor ◽  
The Impact

Abstract One aim of the AML-BFM 98 study was to evaluate prospectively the impact of matched sibling donor (MSD)-SCT in 1st complete remission (CR) in children with high-risk (HR)-AML. Patients: Between 7/1998 and 3/2004 494 children and adolescents were enrolled in the studies AML-BFM 98 and the AML-BFM 98 Interim 2003. Patients with favorable cytogenetics [t(8;21), inv(16), t(15;17)], corresponding morphology (AML FAB M1/2 with Auer rods, M4eo, M3) and < 5% blasts on day 15 were defined as standard risk (SR)-group (n=177). All others were stratified to HR-group (n=317) and eligible for SCT in 1st CR. Out of 275 patients achieving 1st CR (87%) 63 patients had a MSD and 188 had no MSD (intent-to-treat group, ITT) while 24 patients had to be excluded due to missing HLA typing or initial refusal to SCT. Thirty-six patients received MSD-SCT (=as-treated group), another two children were transplanted from a matched unrelated donor (MUD) although an MSD was available. The reasons not performing SCT in 1st CR in the remaining 25 children with a donor available were early relapse (n=7), death in CR (n=2), clinical reasons (n=8), or refusal of SCT (n=8). Chemotherapy (CHT) only was given in 192 patients (n=167 without MSD, n=25 with a MSD). Another 21 children were transplanted from an unrelated donor (n=18), family donor (n=1), haploidentical donor (n=2). The reasons were slow response, very poor cytogenetics or other clinical reasons. Treatment: All patients received double induction and consolidation. MSD-SCT in 1st was scheduled after 4 blocs of treatment. Children who were not transplanted in 1st CR received intensification and a 1-year maintenance therapy. The recommended conditioning regimen consisted in busulfan and cyclophosphamide. Results ITT analysis revealed no significant differences in of 5 year disease-free survival (DFS) and overall survival (OS) between children with or without a donor (no donor vs. donor: DFS 43±4% vs. 47±7% plog rank 0.52; OS 56±4% vs. 58±9%, plog rank 0.16). The as-treated analysis gave similar results: CHT only vs. MSD-SCT: DFS 35±11% vs. 59±9% p Mantel-byar 0.13; OS 59±13% vs. 62±12%, p Mantel-byar 0.51). The major reasons of treatment failures were relapses in all groups [CHT only n=100 (52%), MSD-SCT n=13 (34%), MUD-SCT n=9 (50%)]. A 2nd CR was achieved in 71% of the CHT only group (n=74). After SCT in 2nd CR, OS was 40±6%. By contrast, only two children (9%) of 22 children after relapse following SCT in 1st CR could be salvaged. Severe late adverse events (e.g. severe chronic GvHD CTC grade IV, destruction of big joints, intracerebral bleedings) were more frequent in children transplanted in 1st CR (15%) than in those with CHT only (including SCT in 2nd CR; 5%, p×2< 0.05). Conclusion: In the population-based, prospective multi-center study AML-BFM 98 allogeneic MSD-SCT in 1st CR showed no advantage in children and adolescents with HR-AML. Considering the higher toxicity of allogeneic SCT, in the ongoing trial AML-BFM 2004, this SCT (MSD or MUD) is restricted to patients in 2nd CR and refractory AML.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Allogeneic Bone Marrow Transplantation From HLA Mismatched Family Donors in Children with Aplastic Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 831-831 ◽  
Author(s):  
Hideki Muramatsu ◽  
Hiromasa Yabe ◽  
Ryoji Kobayashi ◽  
Akira Kikuchi ◽  
Kazuko Kudo ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Chronic Gvhd ◽  
Secondary Malignancy ◽  
Unrelated Donor ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Unrelated Donors ◽  
Related Donor ◽  
Family Donor

Abstract Abstract 831 The first-line therapy for children with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-matched family donor, and immunosuppressive therapy (IST) is indicated for patients without HLA-matched family donors. While the standard therapy for children who fail to respond to IST is allogeneic HSCT from an HLA-matched unrelated donor, HSCT from an HLA-mismatched family donor has also been indicated. Compared with unrelated donors, an HLA-mismatched family donor has some advantages especially for children who need urgent transplantation. We analyzed the clinical outcome of 578 children (325 boys and 253 girls) with AA (age, <20 years) who received allogeneic BMT between 1990 and 2009 in Japan, and registered to the Transplant Registry Unified Management Program (TRUMP). The median age at transplantation was 11 years (0–19), and the donors were serological 6/6 HLA-matched related donors (MRD) (n = 312), 1 locus-mismatched related donor (1MMRD) (n = 44), 2–3 loci-mismatched related (haploidentical) donors (n = 9), and HLA-matched unrelated donors (MUD) (n = 213). Causes of deaths were as follows: acute graft-versus-host disease (GVHD) (n = 4), chronic GVHD (n = 4), acute respiratory distress syndrome (n = 2), severe hemorrhage (n = 7), engraftment failure (n = 5), infection (n = 18), idiopathic pneumonia (n = 8), organ failure (n = 19), secondary malignancy (n = 4), and others (n = 4). The probability of severe acute GVHD (grade III–IV) in patients transplanted from 1MMRD (26.9% ± 7.4%) was significantly higher than that in patients transplanted from MRD (4.9% ± 1.3%) (p < 0.001). The probability of 5-year overall survival (5y OS) of patients transplanted from 1MMRD (93.1% ± 3.9%) was comparable to that of patients transplanted from MRD (93.1% ± 1.5%) (p = not significant, NS), but it was significantly better than that of patients transplanted from haploidentical donors (66.7% ± 15.7%, p =.016) and MUD (79.0% ± 2.9%, p =.014). In the subgroup analysis of 1MMRD, no significant difference was observed between HLA class I-mismatched (n = 32) and class II-mismatched patients (n = 12) (5y OS; 93.8% ± 4.3% vs. 91.7% ± 8.0%, p = NS). Comparison of the survival outcome based on the transplant period (1990–1999 vs. 2000–2009) revealed that the probability of 5y OS of patients transplanted from 1MMRD was not significantly different (92.3% ± 5.2% (n = 26) vs. 94.4% ± 5.4% (n = 18), p = NS), while that of patients transplanted from MUD significantly improved in the same period as we reported previously (67.1% ± 5.5% (n = 73) vs. 86.1% ± 3.1% (n = 140), p =.001)(Yagasaki et al., Blood 2011). In multivariate analysis, haploidentical donors (p <.001), MUD (p <.001), age ≥ 10 years (p <.001), and transplant period (1990–1999 vs. 2000–2009, p =.006) were identified as independent covariates associated with unfavorable OS. In summary, our analysis revealed that an HLA-mismatched related donor, especially 1MMRD, could be selected as a donor candidate for children with AA who need urgent transplantation. Disclosures: No relevant conflicts of interest to declare.

Equality Of Access To Transplant For Ethnic Minority Patients Through Use Of Cord Blood and Haploidentical Transplants

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2138-2138 ◽  
Author(s):  
Robert N Lown ◽  
Steven GE Marsh ◽  
Helen Blake ◽  
Sergio Querol ◽  
Irina Evseeva ◽  
...  
Keyword(s):  
Cord Blood ◽  
Ethnic Groups ◽  
Unrelated Donor ◽  
Northern European ◽  
Equal Chance ◽  
Significant Difference ◽  
Unrelated Donors ◽  
The Impact ◽  
Unrelated Adult ◽  
Matched Donor

Abstract It is well accepted that patients of ethnic minorities who lack a sibling donor are poorly represented on the international unrelated donor panels. As recently as 2000, only 30% of such patients were able to find an unrelated donor suitable for transplantation. Historically these patients would have either not been transplanted, or would receive transplants from unrelated donors with two or more HLA mismatches. Continued expansion of the international donor inventory, and the advent of cord blood and haploidentical transplantation has improved the prospects for transplantation for such patients and, through the expertise of search staff within donor registries and histocompatibility laboratories, transplant centres are increasingly able to identify early on those patients who are unlikely to find a well-matched unrelated adult donor. Surprisingly, however, few contemporary data have been published to show the impact of these search strategies and alternative stem cell sources on provision of transplant to those of non-white Northern European origin. We consecutively enrolled and prospectively followed up (from search request to last contact or death) 332 patients referred by four UK transplant centres to the Anthony Nolan Graft Identification and Advisory Service (GIAS) for identification of an unrelated adult donor or cord blood unit. Of these, 248 (74.7%) were of white Northern European (WNE) descent, and 84 (25.3%) non-WNE. The underlying disease did not differ significantly between ethnicities. The median number of UK donors listed on the search report was 8 (range 0 to 3395) and 0 (0 to 42) respectively, and on BMDW 127 (0 to 38245) and 5.5 (0 to 380) respectively. 69.3% of WNE and 20.5% of non-WNE patients found a 10/10 HLA-matched donor at confirmatory typing (CT) (p<0.001); 96.3% of WNE and 61.4% of non-WNE found at least a 9/10 HLA-matched donor (p<0.001). Non-WNE patients had more cord blood transplants (21.3% vs 3.8%, p<0.001) and more haploidentical transplants (10.6% vs 1.3%, p<0.001). There was no significant difference in the number of patients reaching transplant (WNE 63.3%, non-WNE 56.0%, p=0.185) when considering all of the graft sources. Patients of non-WNE background had a significantly slower time from first CT request to identification of an unrelated donor for transplant (median 27 days vs 33.5 days, p= 0.02), and from search request to transplant with any graft source (median 110 days vs 132 days, p=0.03). However, when the cumulative incidence of transplantation with death as a competing risk was considered, there was no difference between ethnic groups (log rank p=0.185, see figure). The median time from search request to transplant by graft source was 120.5 days for adult unrelated donors (n=179), 143 days for cord blood (n=16) and 91 days for haploidentical donors (n=6) (p=0.626). These data show that the chance of receiving a transplant for patients of a non-WNE descent has improved considerably compared to historical literature. The majority of non-WNE patients were able to find a 9 or 10/10 matched donor, and many of those who could not were afforded the option of a cord blood or haploidentical donor transplant within a similar timescale. Whilst times to transplant do remain slightly longer for non-WNE patients, mainly due to a more protracted CT stage, they now stand an equal chance of reaching transplant. However, whether survival following transplant is similar between ethnic groups remains to be seen. Disclosures: No relevant conflicts of interest to declare.

5 Year Results of BMT CTN 0201: Unrelated Donor Bone Marrow Is Associated with Better Psychological Well-Being and Less Burdensome Chronic Gvhd Symptoms Than Peripheral Blood

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 270-270 ◽  
Author(s):  
Stephanie J. Lee ◽  
Brent Logan ◽  
Peter Westervelt ◽  
Corey S Cutler ◽  
Ann E Woolfrey ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Well Being ◽  
Unrelated Donor ◽  
Symptom Scale ◽  
Psychological Well Being ◽  
Donor Bone Marrow ◽  
Patient Reported

Abstract BMT CTN 0201 was a randomized study of unrelated donor bone marrow (BM) vs. peripheral blood (PB) (N=551) in hematopoietic cell transplantation (HCT) for hematologic malignancies. The primary analysis after 2 years of follow up showed similar survival, disease-free survival and treatment-related mortality between the graft types. There was a higher rate of graft failure with bone marrow (9% vs. 3%, p=0.002) and a higher rate of chronic GVHD with peripheral blood (53% vs. 41%, p=0.01). (Anasetti et al, NEJM 2012) Patient reported outcomes (PROs) were collected from patients > 16 years old at enrollment and 0.5, 1, 2 and 5 years after transplantation with the Functional Assessment of Cancer Therapies - Bone Marrow Transplant (FACT-BMT), Mental Health Inventory (MHI), and Lee chronic graft-versus-host disease (cGVHD) symptom scale. At 5 years, 102 BM and 93 PB participants were alive and eligible for the quality of life (QOL) study. Clinically meaningful differences (changes in scores that are noticeable to patients) were considered 0.5 x standard deviation of the total population based on the distribution method. Results: Data as of 5/25/15 were analyzed. 70% completed the pre-randomization assessment, and 74-78% of adult survivors completed the 5 year assessment. Age < 30 at transplant and high risk disease were associated with missing 5 year data, but not graft source. Response rates at 0.5, 1 and 2 years were 28-43% of survivors. There are no differences in any of the primary QOL scores in the first two years after HCT using univariate comparisons, although missing data severely limit conclusions during this period. At 5 years, the FACT-Trial Outcome Index (TOI), the MHI Psychological Well-Being, and the cGVHD symptom scale scores are all significantly better for BM patients, although only the latter two are still significant after adjustment for multiple testing (p<0.0125 because of 4 primary QOL variables). Results were similar when tested in multivariate models adjusting for baseline patient-reported scores and also imputing missing values based on patient characteristics (Table). Of the 7 chronic GVHD subscales, symptoms in the eye, lung, and energy were significantly better with BM (p<0.01). A diagnosis of cGVHD was highly associated with patient-reported cGVHD symptoms but not with QOL or psychological status. Inclusion of extensive cGVHD in the multivariate models did not change the significance of PRO differences suggesting that differences in cGVHD incidence do not explain the PRO findings. With a median follow up of 73 months for survivors, no difference in survival between PB and BM is observed (p=0.84, Figure). Conclusion: At 5 years after transplant, recipients of unrelated donor BM have better psychological well-being and less burdensome chronic GVHD symptoms than recipients of PB. Survival rates are similar. Table. Comparisons of primary QOL variables at 5 years, adjusted for QOL values at baseline and missing data using inverse probability weighting using significant clinical characteristics. QOL scale Bone marrow (n=102) Peripheral blood (n=93) P value Clinically significant difference* Difference between BM and PB (95% CI) FACT-BMT TOI, mean +/- SE (higher scores better) 76.7 +/- 1.6 (n=79) 70.5 +/- 1.9 (n=69) 0.014 8.5 6.2 (1.3-11.1) MHI - Psychological well-being, mean +/- SE (higher scores better) 78.9 +/- 1.7 (n=80) 72.2 +/- 1.9 (n=72) 0.011 8.4 6.7 (1.6-11.8) MHI-Psychological Distress, mean +/- SE (lower scores better) 16.0 +/- 1.3 (n=80) 19.0 +/- 1.5 (n=71) 0.128 6.5 -3.0 (-6.8,0.9) Chronic GVHD symptoms, mean +/- SE (lower scores better) 13.1 +/- 1.5 (n=80) 19.3 +/- 1.6 (n=72) 0.004 7.1 -6.3 (-10.5, -2.0) SE, standard error *0.5 x STD Figure 1. Figure 1. Disclosures Lee: Bristol-Myers Squibb: Consultancy; Kadmon: Consultancy. Maziarz:Athersys: Consultancy, Patents & Royalties, Research Funding; Novartis: Consultancy.

Survival among colorectal cancer patients with a history of previous cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16146-e16146
Author(s):  
Sandi Pruitt ◽  
David E. Gerber ◽  
Hong Zhu ◽  
Daniel Heitjan ◽  
Bhumika Maddineni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Population Based ◽  
Competing Risk ◽  
Cancer Specific Survival ◽  
Risk Of Death ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Impact

e16146 Background: A growing number of patients with colorectal cancer (CRC) have survived a previous cancer. Although little is known about their prognosis, this population is frequently excluded from clinical trials. We examined the impact of previous cancer on overall and cancer-specific survival in a population-based cohort of patients diagnosed with incident CRC. Methods: We identified patients aged ≥66 years and diagnosed with CRC between 2005-2015 in linked SEER-Medicare data. For patients with and without previous cancer, we estimated overall survival using Cox regression and cause-specific survival using competing risk regression, separately by CRC stage, while adjusting for numerous covariates and competing risk of death from previous cancer, other causes, or the incident CRC. Results: Of 112,769 CRC patients diagnosed with incident CRC, 15,935 (14.1%) had a previous cancer – most commonly prostate (32.9%) or breast (19.4%) cancer, with many 7505 (47.1%) diagnosed ≤5 years of CRC. For all CRC stages except IV in which there was no significant difference in survival, patients with previous cancer had modestly worse overall survival (hazard ratios from fully adjusted models range from 1.11-1.28 across stages; see Table). This survival disadvantage was driven by deaths due to previous cancer and other causes. Notably, most patients with previous cancer had improved CRC-specific survival. Conclusions: CRC patients who have survived a previous cancer have generally worse overall survival but superior CRC-specific survival. This evidence should be considered concurrently with concerns about trial generalizability, low accrual, and heterogeneity of participants when determining exclusion criteria. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document