Contrasting the Long-Term Outcome of Reduced-Intensity Allogeneic Stem Cell Transplantation From Related Matched and Mismatched or Unrelated Matched Donor

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2029-2029
Author(s):  
Hui-Sheng Ai ◽  
Xiao-Jun Huang ◽  
Zhen-Hua Qiao ◽  
Jian-Min Wang ◽  
Ying-Min Liang ◽  
...  
Keyword(s):  
Relapse Rate ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Long Term Outcome ◽  
Hematological Diseases ◽  
Matched Group ◽  
Significant Difference ◽  
Reduced Intensity

Abstract Abstract 2029 Reduced-intensity conditioning (RIC) transplantation has been widely used in the treatment of hematological diseases. However, the comparison of long-term outcomes of RIC with HLA-matched, HLA–mismatched and unrelated donor is still lacking. Here, we reported the results of hematological patients treated at the China RIC Cooperative from the HLA-matched, HLA–mismatched and unrelated donor following to RIC. 514 patients with hematological diseases from the China RIC Cooperative Group were enrolled in this study, including 370 in HLA-matched group, 96 in HLA-mismatched group and 48 in unrelated group (table 1). The RIC conditioning regimen was based on fludarabine in combination with antilymphocyte globulin or busulfan or others. The graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A, mycophenolate mofetil and methotrexat. Results showed that 505 patients achieved stable donor chimerism. The incidence of II-IV aGVHD in the HLA-mismatched group was 42.7%, significantly higher than that in the HLA-matched group (21.4%) and the unrelated group (20.8%). The 100-day transplantation-related mortality was 30.2%, 14.5% and 4.2% in the three groups, respectively. The median follow-up time was 57 months (range,7 to 141 months). The overall relapse incidence was 14.8%, including 15.7% in the HLA-matched group, 14.6% in the HLA-mismatched group and 8.3% in the unrelated group. There was no significant difference in relapse incidences in the patients with AL-CR1 and CML-CP (16.4% and 11.2%), as well between the HLA-matched group (16.9% and 16.7%) and the unrelated group (11.1% and 8.8%). For the patients with advanced leukemia, a significantly lower relapse rate was found in the HLA-mismatched group in comparison with that in the HLA-matched group (18% vs 36.2%, p<0.05, Fig. 1).The Kaplan-Meier estimated DFS and OS at 6 years for all of the 514 patients were 58.6% and 61.9% respectively, and those at 11 years were 57.8% and 61.7% respectively. The DFS and OS at 6 years in the HLA-mismatched group was 35.4% and 38.5% respectively, lower than those at 11 years in the HLA-matched group (62.7% and 67.0%, p<0.01) and those at 6 years in the unrelated group (64.6% and 66.7%, p<0.01, Figure 2 A, B). The 11-year DFS for the patients with AL-CR1, CML-CP and MDS/SAA was 68.7%, 68.5% and 73.6% respectively in the HLA-matched group. The 6-year DFS for the patients with AL-CR1, CML-CP and MDS/SAA was 55.6%, 70.7% and 62% respectively in the unrelated group, and 37.5%, 62.5% and28.6% respectively in the HLA-mismatched group. Figure 2 C,D,E£© However, the 6-year DFS in the patients with advanced leukemia was 32.0% in the HLA-matched related group, similar to that in the HLA-mismatched group (31.9%, p£¾0.05, Fig. Figure 2 F). These results indicate that RIC transplantation had similar outcome in the HLA-matched group and unrelated group but better than that from the HLA-mismatched group in haematology diseases. However, for the advanced leukemia patients, the HLA-mismatched transplantation had much lower leukemia relapse rate than in the HLA-matched group. Fig 1: The relapse rate of the patients with advanced leukemia in the HLA-mismatched group and the HLA-matched group. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Stem Cell Transplantation (HCT) Compared to Chemotherapy Only in Acute Myeloid Leukemia (AML) Patients 60 Years and Older: A Center for International Blood and Marrow Transplantation Research (CIBMTR)/ Cancer and Leukemia Group B (CALGB) Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 657-657 ◽  
Author(s):  
Sherif Farag ◽  
Kati Maharry ◽  
Waleska S. Perez ◽  
Mei-Jie Zhang ◽  
John F. DiPersio ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Free Survival ◽  
Prognostic Features ◽  
Allogeneic Hct ◽  
Significant Difference ◽  
Chemotherapy Patients ◽  
Reduced Intensity

Abstract Abstract 657 The outcome of patients aged 60 years or older with AML treated with conventional cytotoxic chemotherapy remains extremely poor with few long-term survivors, irrespective of the type of induction or post-remission treatment intensity or duration. In younger patients, allogeneic HCT performed in first complete remission (CR1) appears to offer a potential advantage in terms of progression-free survival and possibly overall survival (OS) in patients with adverse prognostic features, due at least in part to a graft-versus-leukemia (GvL) effect. Preliminary results of reduced-intensity (RIC) allogeneic HCT performed in older AML patients in CR1 suggest that this approach may improve long-term outcome. However, as patients undergoing allogeneic HCT are likely to be highly selected, it remains uncertain if such an approach will truly improve outcome compared to chemotherapy alone. To investigate this possibility, we compared the outcome of 100 AML patients aged 60-70 years who received RIC allogeneic HSCT in CR1 and were reported to the CIBMTR to that of 96 AML patients treated with only standard induction (daunorubicin and cytarabine ± etoposide) and post-remission chemotherapy on CALGB protocols 9720 and 10201 between January 1998 and October 2006. Patients with therapy-related AML or following an antecedent hematologic disorder were included, along with de novo patients. In the chemotherapy-treated group, only patients who remained in CR1 for at least 4 months were included in order to reduce selection bias. Patients in the HCT cohort were younger than those in the chemotherapy-treated cohort (P<.001; median age 63 v 65 years). There was no significant difference in the distribution of sex, therapy-related leukemia, white blood cell count, FAB classification, or the proportion with normal cytogenetics at diagnosis between the two groups. The time from diagnosis to achievement of CR1 was longer for HCT patients compared to chemotherapy-treated patients (P=.007; median 46 v 38 days). HCT donors were HLA-identical siblings (n=48, 48%) and closely matched unrelated donors (n=52, 52%) and all HCT utilized reduced intensity conditioning plus pharmacologic GVHD prophylaxis. The median follow-up of chemotherapy-treated patients was longer than that of HSCT patients (51 v 30 months). Overall, allogeneic HCT tended to be associated with longer leukemia-free survival (LFS) compared to chemotherapy. The 3-year LFS from CR1 for HCT patients was 34% (95% confidence interval [CI], 24%-44%) compared to 17% (95% CI, 10%-25%) for chemotherapy-treated patients (P=.06). This was largely due to a higher relapse rate (RR); 86% of the chemotherapy patients relapsed compared to only 29% who received HCT (P<.001). However, the non-relapse mortality rate was significantly higher among patients receiving HCT compared to chemotherapy-treated patients (P<.001; 39% v 17%). Survival from CR1 did not differ between the groups (P=.47), with 3 year estimates of 35% (95% CI, 25%-46%) for HSCT patients compared to 25% (95% CI, 17%-34%) for chemotherapy patients. Our results indicate that RIC allogeneic HCT in CR1 in older AML patients is associated with a longer LFS, largely due to a reduction in the RR. Strategies aimed at reducing non-relapse mortality associated with allogeneic HCT, including better graft-versus-host disease prophylaxis and treatment, may lead to a significant improvement in OS for older AML patients. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation (Allo-SCT) in the Management of Advanced Waldenstrom’s Macroglobulinemia (WM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 619-619
Author(s):  
Charalampia Kyriakou ◽  
C. Canals ◽  
A. Sureda ◽  
G. Taghipour ◽  
J. Cornelissen ◽  
...  
Keyword(s):  
Median Time ◽  
Relapse Rate ◽  
Residual Disease ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Mixed Chimerism ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Significant Difference

Abstract Despite effectiveness of standard chemotherapy regimens, complete response is infrequent in WM patients and there is no cure. The role of Allo-SCT has not been extensively explored and the available data are limited. In this retrospective European multicenter study we report the outcome of 106 WM patients (69 male) who underwent an Allo-SCT between 1989 and 2005 and were reported to the EBMT Lymphoma Database. The median age at transplant was 49 years (21–65), and the median time from diagnosis to SCT was 34 months (5–310). The median number of treatment lines prior to allo-SCT was 3(1–10) and 19 patients had failed a prior autograft. Ten (10%) patients were in 1st maximum response (MR), 35 (33%) in PR1, 29 (27%) in PR≥2 and 32 (30%) had refractory disease at the time of transplantation. Forty-four patients were treated with conventional (CT) conditioning protocols; [Cy/TBI n=24, Melphalan/TBI, n=6, BuCy n=14] and 62 with a reduced intensity protocol (RIC); [Fludarabine based regimen n=43, Low dose TBI/Cy n=19] With a median follow up of 31 months (3 to 169) 59 (56%) patients, are alive and free of disease. Forty-eight (45%) patients developed aGVHD [Grades I-II (n=34), Grades III-IV (n=14)] with no statistically significant difference between conventional and RIC groups. Five out of nine RIC patients developed aGVHD following the administration of donor lymphocytes for either residual disease or mixed chimerism. Sixteen patients (15%) developed limited and 11 (10%) extensive chronic GVHD. Seventeen (16%) patients relapsed at a median time of 8 (1–89) months after allo-SCT. Thirty-five (33%) patients died, 5 (5%) from disease relapse or progression and 30 (28%) from regimen toxicity. Non-relapse mortality rates were estimated of 30% and 33%, at 1 and 3 years, respectively, for the CT group, and 24% and 30% for the RIC group of patients. Relapse rates at 1 and 3 years were 10%, 12% for the CT group and 14% and 25% for the RIC. Progression free survival (PFS) rates were 60%, 54% and 54% at 1, 3 and 5 years for the CT and 61%, 44% and 39% for the RIC patients. Overall survival was 65%, 59% and 59% for the CT and 71%, 66% and 66% for the RIC at 1, 3 and 5 years, respectively. Multivariate analysis showed that chemorefractory disease at allo-SCT was associated with a significantly higher relapse rate [p<0.03; 95% CI 1.1–8.9] while the use of TBI in the conditioning regimen with a significantly lower relapse rate [p<0.02; 95% CI 1.1–9.3]. There were no differences in outcome when considering the intensity of the conditioning regimen. In conclusion, allo-SCT is a feasible and well-tolerated procedure in this group of elderly patients with advanced disease. In addition, relapse rate after the allogeneic procedure is low resulting in a good long-term outcome.

The Role of Hematopoietic Cell Transplantation (HCT) for Burkitt Lymphoma: a Report From the Center for International Blood and Marrow Transplant Research (CIBMTR)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2390-2390
Author(s):  
James L. Gajewski ◽  
Jeanette Carreras ◽  
Hillard M. Lazarus ◽  
Ginna G. Laport ◽  
Silvia Montoto ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Unrelated Donor ◽  
Free Survival ◽  
Disease Free

Abstract Abstract 2390 Burkitt lymphoma (BL) is an aggressive B cell lymphoma primarily affecting children and young adults and is characterized by the highest doubling time of any tumor. Cyclical intensive chemotherapy and rituximab confer high complete remission (CR) rates and 80% long term disease free survival in chemotherapy sensitive disease. The role of autologous (autoHCT) or allogeneic (alloHCT) transplant is not well described in BL. We report the outcomes of 241 recipients of HCT for BL between 1985 and 2007 reported to the CIBMTR. Five patients (pts) received syngeneic twin grafts in addition to autoHCT in 113 pts, HLA identical sibling alloHCT (SIB) in 80 pts and mismatched related or unrelated donor (UNR/MM) alloHCT in 48 pts. Baseline patient and disease related risk factors varied significantly between cohorts (table1). The autoHCT cohort had a higher proportion of pts with chemotherapy sensitive disease (86%), peripheral blood grafts (73%) and HCT in first CR (42%). In the UNR/MM cohort, 25% pts were chemotherapy resistant and only 6% were in CR1. The use of autoHCT has declined in recent years with the majority (81%) performed before 2001. Conditioning regimen for alloHCT was myeloablative in 88% (86% and 92% in SIB and UNR/MM respectively). Treatment related mortality (TRM) was higher in alloHCT recipients (table1). Cumulative incidence of relapse/progression at 5 yrs (95% CI) was 44 (35-53)% for autoHCT, 42(31-53)% for SIB and 48 (34-62)% for UNR/MM. For autoHCT, 5-yr progression free survival (PFS) was 48(39-58)%, 78% for those in first CR versus 27% for disease beyond CR1 (p<0.001). For alloHCT, 5-yr PFS was 50% for those in first CR versus 19% for disease beyond CR1 (p=0.001) (figure 1). 5-yr PFS was 30 (20-41)% for SIB and 22 (12-35)% for UNR/MM. Progressive BL was the commonest cause of death. Conclusion: While autoHCT and alloHCT are both feasible in patients with BL, the use of autoHCT appears to be declining in recent years concomitant with the advent of modern chemotherapy. AlloHCT was performed in those with considerably higher risk disease. Approximately one fifth of advanced BL pts receiving alloHCT beyond CR1 had long term disease free survival. Disclosures: No relevant conflicts of interest to declare.

Correlation Between Severity of cGvHD and Transplant Outcome: A Retrospective Monocenter Study Based on NIH Classification,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4088-4088
Author(s):  
Colombe Saillard ◽  
Roberto Crocchiolo ◽  
Sabine Furst ◽  
Jean El-Cheikh ◽  
Luca Castagna ◽  
...  
Keyword(s):  
Stem Cells ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Extensive Form ◽  
Hematopoietic Stem ◽  
Transplant Outcome ◽  
Significant Difference

Abstract Abstract 4088 Background: Chronic graft-versus-host disease (cGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies is associated with lower relapse rate, due to graft-versus-tumor effect. We know that the extensive form is associated with higher transplant-related mortality after myeloablative conditioning regimen, mainly due to infectious complications as a consequence of immunosuppressive treatment. Beside the “classical” Seattle classification (limited or extensive form), a recent classification (from National Institute of Health, NIH) distinguishes three levels of severity: limited, moderate and severe. We compare here both classifications for patients receiving reduced-intensity conditioning (RIC) transplant and looked for any association of cGvHD severity with transplant outcome. Patients and Methods: We evaluated data on all adult patients with hematological lymphoid or myeloid malignancies who received HSCT from related or unrelated donor, using peripheral blood stem cells, after RIC regimens (with fludarabine-busulfan-ATG) between 1998 and 2010 at the Institut Paoli-Calmettes (Marseille, France). Data on main pre- and post-transplant variables were collected; cGvHD was classified according to its presentation and severity (with both Seattle and NIH classifications) and was correlated with overall survival (OS), non relapse mortality (NRM), and relapse. cGvHD was considered as time-dependent variable, and was included in uni- and multivariate models, after adjusting for age, disease risk, HLA compatibility, graft source and comorbidity score. Relapse or death before cGvHD was considered as a competing event. Results: 283 patients were evaluated, 121 have developed cGvHD (27 limited forms and 94 extensive forms), 162 have not, for an incidence rate of 10% and 33% of limited and extensive forms respectively. Median follow up was 607 days, patients had a median age of 50 years, transplanted for acute leukemia (55), lymphoma (78), multiple myeloma (49), myelodysplastic syndrome (24), CLL (12), CML (16) or others malignancies (19). Peripheral stem cells were mostly used (294 versus 20 bone marrow graft). We had 241 related donors and 77 unrelated donors. The median day of cGvHD occurrence was 132, we found 52 de novo forms, 40 quiescent and 26 progressive forms. After reclassification with NIH criteria, we obtained 28 mild, 52 moderate and 41 severe forms. 22 of 27 limited forms were classified as mild, the extensive forms were divided into 49 moderate and 39 severe forms. In multivariate analysis, mild and moderate forms were associated with better OS compared with other groups. Severe cGvHD was associated with significant increase in NRM. Among the other variables, only age was statistically significative in OS and NRM models. Although the incidence of relapse was lower in patients with cGvHD compared with those without, no significant difference was seen between the 3 groups of patients presenting it. Conclusion: Following a fludarabine-busulfan-ATG RIC, it seems that mild to moderate cGVHD forms are associated with better OS than patients without or with severe cGVHD. This is related to lower NRM than patients with severe cGVHD and at least a comparable antitumoral effect with respect to patients without cGVHD. This invites developing strategies limiting severity but not abrogating the effect of cGVHD. Disclosures: No relevant conflicts of interest to declare.

Ex Vivo T Cell-Depleted Haploidentical HCT for Children with Acute Leukemia after a Reduced-Intensity Preparative Regimen Containing Low-Dose TBI

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4673-4673
Author(s):  
Yeon Jung Lim ◽  
Ho Joon Im ◽  
Sung Han Kang ◽  
Hyery Kim ◽  
Kyung-Nam Koh ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Leukemia ◽  
Low Dose ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Reduced Intensity

Abstract Background: Recent advances in haploidentical hematopoietic cell transplantation (HHCT) enabled this transplant using haploidentical family donor to be a viable option for pediatric patients lacking matched related or unrelated donor. In our center, HHCT using ex vivo T cell-depleted (TCD) grafts after reduced-intensity conditioning (RIC) was conducted since 2008. The safety and efficacy of this transplantation modality for pediatric with acute leukemia were investigated. Methods: Thirty-one pediatric patients with acute leukemia received ex vivo T cell-depleted HHCT at Asan Medical Center Children's Hospital between July 2008 and June 2016. Four patients received CD3-depleted grafts and 27 received TCRαβ-depleted stem cells. Among 31 patients, 9 had ALL (3 CR1, 6 CR2-3), 22 had AML (18 CR1-3, 4 NR). Seven patients had relapsed after previous allogeneic HCT. All 31 patients underwent a uniform RIC regimen consisting of low-dose total body irradiation (LD-TBI; 600 cGy), fludarabine (FLU; 180 mg/m2), cyclophosphamide (CY; 100 mg/kg), and rabbit anti-thymocyte globulin (r-ATG; 3 mg/kg). Results: The median age at HHCT was 14 years (range, 1-19). All 31 patients achieved sustained neutrophil engraftment at a median of 10 days (range, 9-17) post-transplant. The cumulative incidence of acute GVHD grade II-III and III were 30% and 21%, respectively. None developed grade IV. Two of 26 evaluable patients developed extensive chronic GVHD. As of July 2016, 18 of the 31 patients survive free of disease with a median follow-up of 26 months (range, 2-98 months). Ten patients have died. Causes of death were relapse (n=9) and disseminated tuberculosis (n=1). Only one patient died of non-relapse cause, leading to TRM of 5.3% at 1 year. EFS and OS at 2 years for all patients were 51% and 60%, respectively. Sixteen patients with AML who received a first HHCT in any CR showed a favorable outcome (EFS of 85%), whereas, 6 patients with ALL who received a first HHCT in CR showed a poor EFS of 28%. In addition, all patients (6 with AML and 3 with ALL) who received a subsequent HCT in CR or were not in remission developed relapse. Conclusions: This study demonstrated that our ex vivo T cell-depleted HHCT using RIC is a feasible therapy with low TRM for pediatric patients with acute leukemia. The outcome of patients with AML who received their first transplant in CR was excellent in this treatment modality. However, the outcome of ALL was poor suggesting that more intensified conditioning regimen may be required for those diseases. Furthermore, an innovative treatment strategy is warranted to improve the outcome for patients with relapsed or refractory acute leukemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comparison of Outcomes of Unrelated BM and CB Transplants in Young Adult Leukemia Patients. Updated Results of Japanese Registration Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 45-45
Author(s):  
Seitaro Terakura ◽  
Yoshiko Atsuta ◽  
Nobuhiro Tsukada ◽  
Takeshi Kobayashi ◽  
Masatsugu Tanaka ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Risk Group ◽  
Unrelated Donor ◽  
Transplant Outcomes ◽  
First Choice ◽  
Significant Difference ◽  
Risk Patients ◽  
Standard Risk ◽  
Mismatch Effect

Abstract Background: Currently, among HLA-8/8, or 7/8 allele-matched unrelated donor (UD) and umbilical CBT (UCBT), HLA-8/8 allele-matched UD transplantation (UDT) showed superior overall survival (OS) to 7/8 allele-matched UDT and UCBT, while a similar OS has been demonstrated between the HLA-7/8 allele-matched UDT and the UCBT. It has been observed that recipients of CB had higher earlier mortality including graft-failure or severe infections. However, less graft-versus-host disease (GVHD) and associated complications brought less long-term mortality, which compensate the early deaths. Thus we hypothesized that UCBT may demonstrate comparable outcomes with 8/8 allele-matched UDT in updated long-term analyses. Methods: The purpose of the current study is to compare the transplant outcomes of 8/8 and 7/8 allele-matched BMT with those of CBT, and redefine the role of CBT. Because the most of UDT in Japan is still BM transplantation, we analyzed the transplant outcomes in younger adult patients (age, 16-50) receiving UCBT in comparison with those receiving 8/8, 7/8 and 6/8 allele-matched unrelated BMT (UBMT) for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) using a Japanese registry database (TRUMP data). Also we included 6 out of 6 HLA-allele data available UCBT so that we could analyze each allele-mismatch effect within UCBT group. Results: A total of 3,062 first transplants between 2001 and 2010 were included. [AML: 8/8 UBMT, 676; 7/8 UBMT, 455; 6/8 UBMT, 204; CB; 617][ALL: 8/8 UBMT, 418; 7/8 UBMT, 267; 6/8 UBMT, 120; CB, 305] For AML, CR1 and CR2 are defined as standard risk and others are as advanced risk. For ALL, CR1 is defined as standard risk and others are as advanced risk disease. Advanced risk patients were significantly more in the UCBT group. With adjusted analyses for AML, UCBT and 8/8 UBMT showed similar OS, while 7/8 and 6/8 UBMT showed inferior OS [8/8 UBMT as reference: CB; Hazard ratio (HR) =1.08 (95% confidence interval (95%CI), 0.91-1.29), p=0.37: 7/8 UBMT; HR = 1.27 (95%CI, 1.06-1.52), p=0.009: 6/8 UBMT; HR =1.33 (95%CI, 1.06-1.67), p=0.015]. The 4-year unadjusted OS was 65.9% (95% CI, 60.6-70.7) for 8/8 UBMT and 61.8% (95%CI, 55.0-67.9) for UCBT in standard risk patients, while 28.1% (95%CI, 21.6-34.9) for 8/8 UBMT and 30.3% (95%CI, 25.0-35.8) for UCBT in advanced risk patients. For ALL, there is no significant difference in OS among 4 groups in adjusted analyses. The 4-year unadjusted OS was 64.3% (95%CI, 57.3-70.5) for 8/8 UBMT and 65.7% (95%CI, 56.1-73.7) for UCBT in standard risk patients, while 28.5% (95%CI, 20.2-37.3) for 8/8 UBMT and 30.2% (95%CI, 21.6-39.2) for UCBT in advanced risk patients. There is no significant difference in the risk of relapse among 4 groups for both AML and ALL. Non-relapse mortality (NRM) in AML after UCBT was comparable with 8/8 UBMT, while 7/8 and 6/8 UBMT had higher NRM [CB; HR =1.12 (95%CI, 0.85-1.47), p=0.43: 7/8 UBMT; HR = 1.51 (95%CI, 1.16-1.96), p=0.002: 6/8 UBMT; HR =1.55 (95%CI, 1.12-2.16), p=0.009]. The 2-year unadjusted NRM of AML for 8/8, 7/8, 6/8 UBMT and UCBT was 16.5% (95%CI, 13.0-20.5), 24.2% (95%CI, 19.1-29.7), 26.0% (95%CI, 18.3-34.4) and 20.0% (95%CI, 15.2-25.3) in the standard risk group, respectively, while 21.4% (95%CI, 15.9-27.4), 30.7% (95%CI, 23.3-38.4), 26.7% (95%CI, 16.8-37.6) and 19.0% (95%CI, 15.0-23.5) in the advanced risk group respectively. For ALL, the adjusted NRM is not significantly different between 8/8, 7/8 UBMT and UCBT, although 6/8 UBMT alone demonstrated higher risk of NRM. To examine the allele-mismatch effect in UCBT group, we further compared OS/NRM of each allele-mismatch UCBT with UBMT in the cox's multivariate analysis [8/8-, 7/8-, 6/8-UBMT, 6/6-, 5/6-, 4/6-, 3/6-, 2/6- and 1/6-UCBT]. Each allele-mismatch UCBT group showed comparable HR with 8/8 UBMT group (Figure). There was no significant difference among each allele-mismatch group. Conclusion: These data suggest that CB may be the first choice alternative to 8/8 UBM for AML. For ALL, 8/8 UBM is the first choice, however, CBT will convey comparable outcomes with 7/8 UBMT. The survival after UCBT is approaching to that after 8/8 UBMT in recent years. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Choice of Treatment for Elderly AML-Patients: 7+3 or Low Doses ARA-C

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5136-5136
Author(s):  
Vera V. Troitskaya ◽  
Elena N. Parovichnikova ◽  
Andrey N. Sokolov ◽  
Alina V. Kokhno ◽  
Zalina T. Fidarova ◽  
...  
Keyword(s):  
Median Survival ◽  
Conflicts Of Interest ◽  
Early Death ◽  
Long Term Results ◽  
Long Term Outcome ◽  
Age Cohorts ◽  
Elderly Aml ◽  
Significant Difference ◽  
Choice Of Treatment

Background Acute myeloid leukemia (AML) in older adults is a biologically and clinically distinct entity. These patients often have comorbidities, and their treatment must be chosen with caution. In AML patients over 60y old, cure rates are under 10% even after intensive chemotherapy (CT). Aim To compare the efficacy of different therapeutic approaches in elderly AML-pts treated in NRCH. Methods From 2002 till 2019, NRCH has conducted a prospective non-randomized study which included 80 AML-patients 60-81y (Me - 67y): 60-65 yy (n=53) and >65y (n=27); M/F - 35/45; de novo AML n=61 (76,25%), AML from MDS - n=13 (16,25%), «secondary» AML - n=6 (7,5%); cytogenetic risk: favorable n=1 (1,25%), intermediate n=49 (61,25%), poor n=30 (37,5%). The patients were stratified to different treatment approaches according to age. Patients 60-70y (n=40) mostly received 1-2 induction cycles 7+3 (ARA-C 100 mg/m2 bid; Dauno - 45-60 mg/m2 ), then 2 consolidation cycles 7+3 (Dauno - 45 mg/m2) and 2 years maintenance (5+5 with 6-MP). Patients >70y (n=22) were usually treated with 1-2 induction and 2 consolidation cycles of low dose Ara-C (LDAC) (10 mg/m2 sc bid, 28-days) and 3 years maintenance with 21-28-days LDAC. In some cases, fit patients over the age of 70y have got 7+3 (n=5) and some younger with comorbidities - LDAC (n=13). The analysis was done in May 2019. We evaluated treatment outcome according to age, cytogenetics and type of CT. Results The CR rate in the whole group of elderly AML-pts was 57,5% (46/80) with a median CR-duration - 10 mon (1-138 mon), early death - 16,25% (13/80) and resistance - 26,25% (21/80) with no major differences in the two age cohorts (<>70y). In order to assess of the efficacy of two chemotherapy options we have compared 7+3 and LDAC in patients aged 60-65 and older. In patients aged 60-65 CR-rate was higher -75% (21/28) after 7+3 vs 50% (2/4) after LDAC, with less resistant forms - 7% (2/28) vs 25% (1/4), respectively. In > 65y group CR-rate was identical in pts after 7+3 (47%, 8/17) and after LDAC (55%, 17/31) with similar numbers of resistant forms: 41% vs 29%. Early death rate did not differ among the groups. There was statistically higher CR-rate and lower resistant forms on 7+3 in pts aged 60-65 compared to older pts. - 75% vs 47% (p<0.05) and 7% vs 41% (<0.005) (Tab.1). Long-term results in the whole cohort of elderly patients were as follows: 1-y OS - 46%, DFS - 52,2%, 5-y ОS - 13%, DFS - 9% with high relapse rate (70%) development, mostly with early occurrence (Me - 12.8 mon). The median survival was statistically longer in patients aged 60-65y (n=32) comparing to older ones (n=48) - 15.4 vs 8 mon, respectively (p=0.0542), but DFS was equal (Fig.1). Higher incidence (87% vs 74%) and earlier relapse development (12 vs 16 mon) were registered in the group with poor cytogenetics comparing to favorable/intermediate (p=0,022). We didn't observe significant difference in long-term outcome of AML-pts older or younger 70y. Standard LDAC duration is 10-14 days, twice less than we used in our study. A landmark-analysis (from day 30 of induction) has shown that, if the 1st course-duration was less than 28 days, the median survival was shorter - 5,9 mo in comparison with 14,9 mo in pts with 28-days LDAC (p=0.12). The efficacy of 28-days LDAC was very similar to 7+3, mainly in patients aged 66 and older (Fig.2). Conclusion The outcome in elderly AML-patients is determined by age (more or less 65y) and the group of cytogenetic prognosis (poor vs favorable/intermediate). Intensive induction (7+3) is more preferable in patients aged 60-65 y as it produced the higher CR-rate and less resistant forms, results that are comparable to younger AML-patients. In patients older than 65y - CR-rate after 7+3 or 28-day LDAC was identical, and 28-days LDAC may become the choice of treatment for patients older than 65y. However long-term results are generally poor so new therapeutic strategies for elderly AML-patients are highly needed. Disclosures No relevant conflicts of interest to declare.

Second Transplants in Relapsed Multiple Myeloma (MM): Autologous (AHCT) Versus Non-Myeloablative/Reduced Intensity (NST/RIC) Allogeneic Transplantation (AlloHCT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 824-824 ◽  
Author(s):  
Cesar O. Freytes ◽  
David H. Vesole ◽  
Xiaobo Zhong ◽  
Jennifer Le-Rademacher ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Lower Probability ◽  
Unrelated Donor ◽  
Karnofsky Performance Score ◽  
Risk Of Death ◽  
Significant Difference ◽  
Reduced Intensity

Abstract Abstract 824 There is no standard therapy for MM relapsing after autologous hematopoietic cell transplantation (AHCT). A second AHCT can result in additional progression-free survival (PFS). Nonmyeloablative/reduced intensity conditioning (NST/RIC) allogeneic transplantation (AlloHCT) has the advantages of a tumor-free graft and the potential of a graft-versus-myeloma (GVM) effect. Few studies have compared second AHCT vs. NST/RIC AlloHCT. We compared the outcome of second AHCT or NST/RIC AlloHCTafter relapse from prior AHCT in patients with MM reported to the CIBMTR from 1995–2008. Recipients of planned tandem transplants, AlloHCT for graft failure or second malignancies and myeloablative alloHCT were excluded. 137 patients underwent second AHCT and 152 underwent NST/RIC AlloHCT (32 HLA-identical sibling and 120 unrelated donor). The table below illustrates clinical characteristics and patient outcomes. AlloHCT recipients were significantly younger (median 53 years [yrs] of age vs. 56 yrs in the AHCT cohort (p < 0.001). The groups were similar in Karnofsky performance score (KPS) and gender. Conditioning regimens differed between groups. In the AHCT cohort, 85% were melphalan based. In the NST/RIC alloHCT cohort, 38% received melphalan + other drugs and 24% received total body irradiation +/− other drugs but no melphalan (p <0.001). Time from 1st to 2nd transplant was significantly shorter for the AlloHCT cohort (30 vs. 23 months, p = 0.014). Acute graft-versus-host disease (GVH) was 35% at 60 days while chronic GVHD was 44% at 36 months.Patient CharacteristicsAutologousAllogeneicP-valueNumber of patients137152Age at 2nd transplant, median (range), years56 (28–65)53 (32–65)0.001*Gender    Male84 (61)90 (59)0.720Karnofsky Score pre-transplant    ≥90%68 (50)76 (50)0.884Time from 1st to 2nd transplant, months, median (range)30 (6–122)23 (6–78)0.014*    6–24 months44 (32)78 (51)0.001*    >24 months93 (68)74 (49)OutcomesTreatment-related Mortality (TRM)12 months2 (1–5)13 (8–19)<0.001*60 months4 (2–8)15 (10–21)<0.001*Relapse/Progression12 months51 (43–58)72 (64–79)<0.001*36 months82 (76–88)80 (73–86)0.655Progression-free survival12 months47 (40–54)15 (10–21)<0.001*36 months13 (9–19)6 (3–10)0.038*Overall Survival (OS)12 months83 (77–89)51 (42–58)<0.001*36 months46 (37–54)20 (14–27)<0.001*60 months29 (21–38)9 (5–15)<0.001**Significant difference The most common cause of death in both cohorts was progression of MM. On multivariate analysis risk of death was higher for alloHCT (HR 2.38, p < 0.001), KPS < 90 (HR 1.96, p < 0.001), and year of transplant (2004 or earlier, HR 1.77, p = < 0.001). AlloHCT was associated with significantly higher risk of TRM (HR 7.14, p < 0.001). Durie-Salmon Stage III was associated with a higher risk of relapse (HR 2.70, 95% CI: 1.93–3.80, P<0.001) and treatment failure in the alloHCT group (HR 3.05, 95% CI: 2.20–4.22, p < 0.001). We conclude that patients with MM who underwent NST/RIC alloHCT after AHCT failure experienced higher TRM and lower probability of survival compared with those who received second AHCT. Because genetic risk data were not available for these patients, we cannot exclude the possibility that the alloHCT population was a higher risk population. Despite this limitation, our data demonstrate that the value of alloHCT after relapse from prior AHCT is limited. Disclosures: No relevant conflicts of interest to declare.

Reduced Intensity Conditioning with Fludarabine/Busulfan 6.4mg/Kg Results In High Donor Chimerism and Low Toxicity In Both Related and Unrelated Allo-SCT for Hematologic Malignancies.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4519-4519
Author(s):  
Steven C Goldstein ◽  
Selina M. Luger ◽  
Noelle Frey ◽  
Alexander Perl ◽  
Edward A Stadtmauer ◽  
...  
Keyword(s):  
Steady State ◽  
Conflicts Of Interest ◽  
Wide Spectrum ◽  
Hematologic Malignancy ◽  
Pharmacokinetic Analysis ◽  
Unrelated Donor ◽  
Pharmacokinetic Data ◽  
Donor Chimerism ◽  
Significant Difference ◽  
Reduced Intensity

Abstract Abstract 4519 Although the combination of fludarabine and busulfan is commonly used for non-myeloablative, reduced intensity (RIC), and myeloablative conditioning prior to sibling and unrelated allotransplantation, there is a wide spectrum of reported doses which range in fludarabine dose between 120 – 180mg/m2 and busulfan doses between 3.2 and 16mg/kg. Many reports include third agents or serotherapy for T-cell depletion, making retrospective comparisons difficult. Across the spectrum of published fludarabine/busulfan regimens, our investigation of fludarabine at 120mg/m2 falls into the lower range of reported flu doses, while 6.4mg/kg IV Busulfan (bu) has been studied at only a few centers. Very little busulfan pharmacokinetic data has been reported at this dose. We report our experience with fludarabine (30mg/m2/d × 4 days =120mg/m2) and IV busulfan (0.8mg/kg × 8 doses =6.4mg/kg) in 76 consecutive patients (pts) undergoing RIC with Peripheral Blood Stem Cell (PBSC) allografting for hematologic malignancy transplanted at our center from 2006 to March, 2010. GvHD prophylaxi included methotrexate in all pts with either CSA (37) or tacrolimus (38); 13 recipients of tacrolimus also received maraviroc through d30 on a phase I/II trial, and 1 pt received CSA/MMF. Therapy was not modified for unrelated donor source or mismatch. Median age was 60. Donor graft source was sibling PBSC in 35, sibling bone marrow (BM) in 1, unrelated PBSC in 39 and unrelated BM in 1. 47% (36/76) of patients had either AML (19) or MDS (17). The remaining diagnoses included CLL (4), MCL (3), CTCL (6), T-NHL (2), follicular NHL (7), HD (8), MM (3), MF (3), other (4). With a median follow-up of 8.2m (range 0–39m) for all patients, and median f/u for surviving pts of 10.7m (range 0–39m), probability of overall survival at 2 years is 35%. Early non-relapse mortality at 100 days was 9% (7/76). Disease progression accounted for 55% (24/44) of deaths to date. The incidence of grade II-IV acute graft vs host disease (GvHD) was 53% and there was no statistically significant difference in acute GvHD between patients receiving csa/mtx and tac/mtx. Of note, no difference in survival or incidence of GvHD was noted between recipients of 36 sibling vs 40 unrelated stem cells grafts. Donor chimerism of greater than 95% at day 100 was achieved in 39/52 (75%) patients and greater than 90% in 45/52 (86%) patients. Very limited pharmacokinetic data has been reported after RIC conditioning using busulfan; we therefore calculated steady state concentrations in 25 patients. Busulfan pharmacokinetic analysis following the initial dose achieved a concentration steady state between 600–900ng/mL in 56% (14/25) of patients, which is consistent with our full dose busulfan PK experience, but over 2 days instead of 4. In 25 pts, median busulfan level was 856 ng/mL., average busulfan level was 852 ng/mL with a range 610–1544ng/mL. Correlation of bu levels to outcomes will be presented. We conclude that fludarabine 120mg/m2 and IV busulfan 6.4mg/kg provides durable engraftment with acceptable treatment related toxicity in both sibling and unrelated recipients. There was no difference in GVHD between recipients of MTX with either CSA or Tac. Our data suggests that additional agents such as TBI, or ATG, may not be required during conditioning in the unrelated setting in light of the similar outcomes between sibs and unrelated recipients using a two-drug regimen. Disclosures: No relevant conflicts of interest to declare.

Dual Cord Blood Unit (dCBU) Transplantation Increases Short-Term Morbidity, but Has Similar Long-Term Outcome Compared to Matched Unrelated Donor (MUD) Transplantation After Myeloablative Conditioning.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3137-3137
Author(s):  
Matt Kalaycio ◽  
Brian J. Bolwell ◽  
Lisa Rybicki ◽  
Edward Copelan ◽  
Hien K. Duong ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Term Survival ◽  
Long Term Outcome ◽  
Gvhd Prophylaxis ◽  
Significant Difference ◽  
Cell Source ◽  
Matched Sibling

Abstract Abstract 3137 In the absence of a matched sibling donor for allogeneic hematopoietic cell transplantation (HCT), a MUD is the most often used alternative hematopoietic cell source. Unfortunately, many patients do not have a well-matched MUD. For these patients, CBU transplant is a viable alternative donor source. To optimize hematopoietic engraftment in adult recipients two CBU are often required. We offer dCBU transplantation to patients lacking matched sibling and unrelated donors. This report compares outcomes between those treated with dCBU and MUD HCT at our institution. From 8/7/2009 through 12/2011, 22 hematologic malignancy patients received dCBU transplants using the conditioning regimen and GVHD prophylaxis described by the group at the University of Minnesota (Barker et al, Blood. 105: 1343, 2005). Thus, we treated patients with fludarabine 75mg/m2 D-8 to D-6, cyclophosphamide 120mg/kg D -7 to D -6, and total body irradiation (TBI) 1320 cGy D -4 to D -1. GVHD prophylaxis included cyclosporine and mycophenolate. We then selected 42 patients treated with MUD HCT (40 well-matched, 2 partially matched) for similar diagnoses from our database as a comparator group. Patients with MUD donors were treated with either etoposide 60mg/kg and TBI 1200cGy if they had acute lymphoblastic leukemia, or busulfan 16mg/kg orally (or the equivalent administered intravenously) D -8 to D -4 and cyclophosphamide 120mg/kg D -3 to D -2. GVHD prophylaxis for MUD patients included tacrolimus and methotrexate, except in one case where mycophenolate was substituted for methotrexate. The median age of the patients was 49 years (range 20–62 years) with no significant difference between treatment groups. Neither were there differences in diagnoses, HCT-comorbidity index, time from diagnosis to transplant, disease status, or CMV status. However, there was a significant difference with regard to race with 24% of dCBU HCT in African-American patients compared to none of the MUD HCT (P<0.001). Patients with MUD HCT recovered neutrophils and platelets faster (median 16 and 24 days respectively) compared to dCBU HCT (median 27 and 52 days respectively; P<0.001) resulting in shorter length of stay (median 29 versus 49 days; P<0.001) and contributing to a trend toward improved 100 day mortality (17% vs 38%; P=0.06). There was no significant difference in the incidence or severity for either acute or chronic GVHD between the groups. However, the incidence of infection was significantly greater with dCBU HCT (P<0.001). There was also a trend toward greater non-relapse mortality among patients treated with dCBU HCT(P=0.07) all of which occurred within the first 6 months of transplant. Cox proportional hazards analysis was used to identify univariable and multivariable prognostic factors for overall (OS) and relapse-free survival (RFS). Only age (OS: HR1.66; 95% CI 1.08–2.56; P=0.020. RFS: HR1.61; 95% CI 1.07–2.42; P=0.023) and CMV positivity in either donor or recipient (OS: HR 2.61; 95% CI 1.02–6.65; P=0.044. RFS: HR 2.71; 95%CI 1.07–6.86; P=0.035) were significant risk factors. Cell source did not significantly impact either RFS or OS (See figure). We conclude that although dCBU HCT results in increased early morbidity, there is no significant difference in risk for GVHD, and long-term survival outcomes are similar compared to MUD HCT. dCBU HCT is a useful alternative for patients lacking sibling and MUD donors. Disclosures: No relevant conflicts of interest to declare.

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