Comparison of 200 cGy vs. 400 cGy Total Body Irradiation (TBI) When Used with Fludarabine for Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation (RIC AHSCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2003-2003
Author(s):  
Ronald Sobecks ◽  
Robert Dean ◽  
Lisa Rybicki ◽  
Josephine Chan ◽  
Karl Theil ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Disease Relapse ◽  
Hematopoietic Stem ◽  
Diagnostic Categories ◽  
Unrelated Donors ◽  
Matched Sibling ◽  
Total Body

Abstract Fludarabine(FLU) and 200cGy TBI is commonly used for RIC AHSCT, but we observed 12% graft rejections and a 43% incidence of disease relapse when used at our institution. We hypothesized that this might be improved with dose escalation of TBI to 400cGy. From 12/03–4/07 40 pts with hematologic malignancies received RIC AHSCT using FLU 30 mg/m2/d on days -5, -4 and -3 and then TBI 200cGy on days -1 and 0. Our analysis compared outcomes with 42 historical control pts who received 200cGy TBI from 1/00–11/03. Matched sibling donors (MSD) were used for 32(76%) pts in the 200cGy group and 26 (65%) in the 400cGy group (p=0.27); other pts had 8/8 HLA matched unrelated donors (MUD). MSD pts received cyclosporine/mycophenolate and MUD pts received tacrolimus/mycophenolate. There were no differences in diagnostic categories between the 200cGy and 400cGy groups, which included 19(45%) and 22(56%) pts with myeloid (MY) diseases, respectively, (AML most common for both) while the remaining pts with lymphoid (LY) diseases had NHL most commonly. No other baseline characteristics differed between the groups. 200cGy pts received a higher median CD34+ cell dose (6.77 vs 4.93 × 106/kg, p<0.001), more often required 2nd transplants (5 vs 0; p=0.033) and donor lymphocyte infusions (5 vs 1; p=0.08) post RIC AHSCT. There were no differences in incidence or severity of acute/chronic GVHD, time to platelet and neutrophil engraftment, CMV, other infections or non-infectious toxicities. Although fewer 400cGy pts had graft rejection (2 vs 5), this did not reach statistical significance. Achievement of T cell complete donor chimerism (CDC) was similar between the 200cGy and 400cGy pts (85% vs 87%; p=0.61) as was the median time to achieve CDC (57 vs 40 days, respectively; p=0.80). Median times to achieve CDC for LY vs. MY pts were: 41 vs. 77 days (200cGy; p=0.26); and 30 vs. 61 days (400 cGy pts; p=0.29), respectively. Relapse rates for 200cGy and 400cGy groups were 43% vs. 30%; MY pts 42% vs 27% and LY pts 44% vs 29%, respectively. 12(29%) of the 200cGy pts and 23(58%) of 400cGy pts are alive at median follow-ups of 52 vs 16 mos, respectively. There was a trend toward higher 100 day mortality in the 400cGy pts with 7(18%) deaths (3 disease relapse, 2 cardiac, 1 GVHD, 1 graft failure) vs 2(5%) in the 200cGy pts (2 GVHD) (p=0.06). At current follow-up there are no significant differences in overall(OS) and relapse-free survival(RFS) between the groups. However, in the 200cGy group LY pts’ OS was superior to MY pts (p=0.047, Figure) but this difference was no longer observed upon escalating to 400cGy. This may be due to more comparable RFS between MY and LY pts in the 400cGy pts (p=0.56) than in the 200cGy group (p=0.07). We conclude that 400cGy TBI with FLU for RIC AHSCT is well tolerated and further follow-up is needed to determine if outcomes are superior to those with 200cGy TBI. Future investigation of strategies to further intensify RIC may be appropriate, particularly for pts with MY disease. Figure Figure

Impact of HLA Class I Typing-Resolution and Mismatches on Survival and Graft-Versus-Host Disease in Patients after Hematopoietic Stem Cell Transplantations from Unrelated Donors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2060-2060
Author(s):  
Miroslaw Markiewicz ◽  
Jerzy Wojnar ◽  
Malgorzata Krawczyk-Kulis ◽  
Iwona Wylezol ◽  
Sebastian Giebel ◽  
...  
Keyword(s):  
High Resolution ◽  
Relapse Rate ◽  
Graft Failure ◽  
Statistical Significance ◽  
Chronic Gvhd ◽  
Hla Class I ◽  
Class I ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Grade 3

Abstract We analyzed 150 consecutive patients (pts) transplanted from unrelated donors (URD) at single institution- Silesian Medical Academy in Katowice- with use of the same standard operating procedure from February 1997 until December 2004 for CML (74 pts), AML (28), ALL (27), SAA (9), MDS (7), MM (1), NHL (1), PNH (1), OMF (1), bi-phenotypic AL (1). 92 pts were transplanted from matched donors, including 59 with complete 10 alleles (HLA-A,B,C,DRB1,DQB1) high resolution (HR) DNA-typing; and 33 with first class match established on base of low-resolution (LR) (13), serological (7) or un-complete typing without HLA-C (13) and second class HR typing. 58 pts were transplanted from mismatched donors (first class typing was HR in 43, LR in 14 and serological in 1 pt): 22 with single allelic mismatch (2 HLA-A, 7-B, 6-C, 7-DQB1), 33 with single HLA-C antigen mismatch and 3 with double mismatches (2 B+C, 1 C+C). Survival advantage at 4 years, although without statistical significance (p=0.16), was observed in the group of pts transplanted from 10/10 alleles matched donors (36+/− 11%) over those with mismatched donors (24+/− 11%). Oppositely, pts transplanted from matched donors who were not completely typed in HR did not achieve better survival (23+/− 17%). Poorest survival (13+/− 12%, p=0.007) was observed in patients transplanted from mismatched homozygous donors (n=10). The risk of acute GVHD grade 3–4 was increased (p=0.007) in pts with mismatched donors (31+/− 6%) when compared to matched completely typed in HR (10+/− 4%). Also the rate of graft failure tended to be lower in pts with matched than mismatched donors (5.1% versus 10.2%, p=0.25). In contrast, relapse rate was lower in mismatched (23+/− 10%) than in HR matched pts (34+/− 12%, p=0.55) what may reflect better GVL effect in mismatched transplant recipients. Unexpectedly, the rate of chronic GVHD was similar in pts with 10/10 alleles matched and mismatched donors (40+/− 10% versus 42+/− 9%, p=0.75). These results indicate that complete high resolution HLA class I typing is necessary for adequate selection of unrelated donors. Class I HLA-B and -C mismatches influence both survival and serious a-GVHD incidence. 10/10 alleles matched mismatched p survival at 4 years 36+/− 11% 24+/− 11% 0.16 aGVHD grade 3–4 10+/− 4% 31+/− 6% 0.007 graft failure rate 5.1% 10.2% 0.25 relapse rate 34+/− 12% 23+/− 10% 0.55 cGVHD 40+/− 10% 42+/− 9% 0.75 10/10 alleles matched mismatched homozygous donors p survival at 4 years 36+/− 11% 13+/− 12% 0.007

Prospective Evaluation Of Allo-HSCT From Haploidentical-Related Donors Compared With Matched Sibling Donors and Unrelated Donors For Patients With Hematological Malignancies: Results From An Open-Label Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3338-3338
Author(s):  
Yi Luo ◽  
Haowen Xiao ◽  
Xiaoyu Lai ◽  
Jimin Shi ◽  
Yamin Tan ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Prospective Trial ◽  
Hematologic Malignancies ◽  
Treatment Schedule ◽  
Hematopoietic Stem ◽  
High Risk Patients ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Matched Sibling

Abstract Introduction The order of alternative donor selection for hematopoietic stem cell transplantation (HSCT) for patients with hematologic malignancies has not been addressed. We performed the first prospective trial to compare the effect of HSCT from matched sibling donors (MSDs), unrelated donors (URDs) and haploidentical- related donors (HRDs) in a contemporary protocol. Methods From 2008 to 2012, 234 patients with hematologic malignancies were enrolled. The treatment schedule was as follows: if a fully MSD was available, patients were assigned treatment with MSD-HSCT. If an MSD was unavailable, a suitably matched URD was used as the alternative, where a suitable match involved matching more than 8 of 10 HLA-A, -B, -C, -DRB1and DQ allele loci ( ¡Ý 8/10) and at least 5 of 6 matching HLA-A, -B, and -DRB1 antigen loci. If only URDs with > 2 mismatching allele loci were available, patients were allowed treatment with HRD-HSCT. Results (1) Sixty-eight patients underwent MSD-HSCT, 98 patients underwent URD-HSCT, and 68 patients underwent HRD-HSCT (Table 1). (2) Grades II¨CIV and severe aGVHD were all significantly more frequent in patients undergoing HRD-HSCT compared with those undergoing MSD-HSCT (II¨CIV: 42.6% vs 19.1%, P = 0.0015; severe aGVHD: 17.65% vs 5.88%, P = 0.03). However, the incidences of II¨CIV and severe aGVHD were comparable in patients receiving transplants from HRDs to those from URDs (II¨CIV: 42.6% vs 40.8%, P = 0.89; severe aGVHD: 17.65% vs 13.27%, P = 0.48). The incidence of cGVHD was not significantly affected by donor types. (3) The 4-year incidence of relapse was not significantly affected by donor types according to all patients (24.2% in the MSD cohort, 22.8% in the URD cohort, 11.9% in the HRD cohort, P > 0.05). However, after controlling for high-risk patients, a superior graft-versus-leukemia (GVL) effect was observed in patients undergoing HRD-HSCT compared to MSD-HSCT or URD-HSCT. In high-risk patients receiving MSD, 36.8% experienced relapse, as did 33.6% in the URD cohort, but the incidence decreased to11.1% in the HRD cohort (MSD vs HRD, P = 0.015; URD vs HRD, P = 0 .028). (4) HRD-HSCT yielded comparable rates of 4-year overall survival (OS) and disease-free survival (DFS) to MSD-HSCT ( OS: 66.4% vs 79.5%, P = 0.071; DFS: 66.4% vs 78.2 %, P = 0.109) or URD-HSCT (OS: 66.4% vs 59%, P = 0.952; DFS: 66.4% vs 58.1%, P = 0.864) (Figure 1). Conclusion Our data provide convincing clinical evidence to support the use of HRDs, as well as URDs, can be selected as first-line alternative donors, especially for high-risk patients. Disclosures: No relevant conflicts of interest to declare.

Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Survival for Patients with Chronic Myelomonocytic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4347-4347 ◽  
Author(s):  
Piyanuch Kongtim ◽  
Uday R. Popat ◽  
Antonio M. Jimenez ◽  
Sameh Gabella ◽  
Riad O. El Fakih ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Hypomethylating Agents ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Unrelated Donors ◽  
Conditioning Regimens

Abstract Introduction Allogeneic hematopoietic stem cell transplant (allo-SCT) is the only curative treatment modality for patients with CMML. Here we retrospectively reviewed the data for patients with CMML who received an all-SCT at our institution to identify factors associated with improved survival and determine whether treatment with hypomethylating agents (HMA) before transplant improves survival for these patients. Methods All 83 patients 18 years of age or older with a diagnosis of CMML confirmed at The University of Texas MD Anderson Cancer Center who underwent allo-SCT between April 1991 and December 2013 were identified through review of the institutionÕs medical records and included in this analysis. Forty, 7, and 36 patients had CMML-1, CMML-2 and CMML that had progressed to AML (CMML/AML) respectively. The median age was 57 years. CMML specific cytogenetic risk at diagnosis (Such E, hematologica, 2011) was good, intermediate, and high risk in 46, 19, and 18 patients respectively. Seventy-eight patients received induction treatment before transplant, 37 receiving HMA (either 5-azacytidine or decitabine) for at least 3 courses and 41 receiving 1-2 courses of cytotoxic chemotherapy. Among the patients who received induction therapy, 15 patients in HMA group and 9 patients in convention chemotherapy group achieved a complete remission before transplant. Thirty, 47 and 6 patients received transplants from matched related donors (MRD), matched unrelated donors (MUD), and mismatched related or unrelated donors (MMD), respectively. The sources of hematopoietic stem cells were peripheral blood for 48 patients (57.8%) and bone marrow for 35 patients (42.2%). Conditioning regimens varied; most patients received either fludarabine in combination with busulfan or fludarabine combined with melphalan. Sixty-four patients received myeloablative and 19 patients received reduced intensity conditioning regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Patient and transplant characteristics did not significantly differ between the patients treated with HMA and the patients treated with conventional chemotherapy or given supportive care alone. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), Treatment related mortality (TRM), relapse incidence through last follow-up and incidences of acute GVHD and chronic GVHD. All of these outcomes were measured from the time of allo-SCT. Results Median follow up duration for 29 survivors was 48 months. Seventy-five patients engrafted (90.4%) with median time to neutrophil and platelet engraftment of 13 and 15 days respectively. Patients treated with a HMA had a significantly lower cumulative incidence (CI) of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03), whereas TRM at 1 year post-transplantdid not significantly differ between the groups (27% and 30%, respectively; p=0.84). Acute GVHD all grades and grade 2-4 were seen in 28.2% versus 35.8% (p=0.05) and 12.8% versus 11.3% (p=0.72) in patients who received a HMA compared to those who treated with other agents respectively. CI of chronic GVHD was 35% in patients treated with a HMA versus 19.2% in those treated with other agents (p=0.36) while CI of chronic extensive GVHD was seen in only 26.7% versus 19.2% respectively (p=0.64). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a HMA (43%) than in those who received other treatments (27%; p=0.04) (Figure 1). However, therapy with HMA before transplant did not significantly influence the 3-year OS rate (45% in those treated with HMA and 39% in those treated with other agents; p=0.22). The independent prognostic factors for PFS were a blast count of < 5% before transplant (HR 0.36, 95%CI 0.14-0.78), treatment with a HMA (HR 0.44, 95% CI 0.23-0.86), a transplant from an MRD (HR 0.41, 95% CI 0.22-0.94), development of grade 2-4 acute GVHD (HR 2.7, 95% CI 1.27-5.77), and development of chronic GVHD (HR 0.15, 95% CI 0.05-0.45). Conclusion We conclude that treatment with hypomethylating agents before allo-SCT may improve survival in patients with CMML. Figure 1. Progression free survival Figure 1. Progression free survival Disclosures Alousi: Therakos, Inc: Research Funding. Andersson:Otsuka Research and Development, Inc.: Consultancy.

scholarly journals Similar Incidence of Severe Acute Gvhd and Less Extensive Chronic Gvhd in PBSCT from Unmanipulated Haploidentical Donor Compared with That from Matched Sibling Donor for Patients with Hematologic Malignancies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1964-1964
Author(s):  
Honghua Li ◽  
Wenrong Huang ◽  
Chunji Gao ◽  
Liping Dou ◽  
Fei Li ◽  
...  
Keyword(s):  
Cohort Study ◽  
Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem ◽  
Sibling Donor ◽  
Matched Sibling ◽  
Similar Incidence

Abstract Unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HCT) resulted in encouraging outcomes for treatment of hematologic malignancies and become an alternative option in case of lacking HLA matched sibling donor (MSD). Transplantation with G-CSF mobilized peripheral blood stem cell (PBSCT) has been a stable transplant setting with MSD. Unmanipulated haploidentical donor (haplo-PBSCT) has been applied in patients with hematologic malignancies. However, the characteristics of graft-versus-host disease (GVHD) in unmanipulated haplo-PBSCT are not clear. Here, we report the results of a cohort study on the clinical features of acute and chronic GVHD in haplo-PBSCT compared with PBSCT from MSD in patients with hematologic malignancies. PATIENTS AND METHODS Between July, 2007 and June, 2014, 94 patients with hematologic malignancies received haplo-PBSCT and 100 patients received PBSCT from MSD consecutively at our unit (Table 1). The PBSCs were collected on day 5 and 6 after 4 days of rhG-CSF (5 mg.kg¨C1 °¤day¨C1), then were infused on the day of collection. The conditioning regimen consisted of Bu (9.6 mg.kg-1, iv, days -10~-8), Carmustine, (250 mg.m-2, day -5), cytarabine (8 g.m-2, days -7~-6), CY (120mg kg-1, days -4~-3). Antithymoglobulin (ATG, rabbit; 10 mg.kg-1, days -5~-2) was used for haplo-PBSCT. All recipients received cyclosporine A, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. The endpoint of the last follow-up for all surviving patients was July 15, 2015. RESULTS Among the patients with acute GVHD, there was no difference of the rate of the involved organs between these two groups (skin: 67.4% vs 68.0%, p=1.000; liver: 15.2% vs 20.0%, p=0.742; gut: 33.3% vs 32%, p=1.000). Haplo-PBSCT was associated with higher incidence of acute GVHD grade 2-4 (HR: 3.04, 95% CI: 1.55-5.98, p=0.001) and lower incidence of extensive chronic GVHD (HR: 0.49, 95% CI: 0.24-0.99, p=0.047) compared with MSD PBSCT. There was no difference of the incidence of acute GVHD grade 3-4 between these two groups (haplo-PBSCT, 9.6% vs MSD PBSCT 8.9%, p=1.000). According to NIH criteria, the incidence of severe chronic GVHD was lower in haploidentical group (13.6%) compared with MSD group (40.5%, p=0.041). There was no difference of those for mild and moderate chronic GVHD (mild: 27.3% vs 13.5%, p=0.189; moderate: 59.1% vs 45.9%, p=0.422). CONCLUSION In this cohort study, haplo-PBSCT was associated with similar incidence of severe acute GVHD, lower extensive chronic GVHD and lower severe chronic GVHD compared with MSD-PBSCT. It suggested the potential advantage of ATG in improvement of long-term quality of life of the transplant recipients. Table 1. Characteristics of patients and donors Haploidentical donor, n = 94 Matched sibling donor, n = 100 P value Gender, n (%) Receipt, male 73 (77.7) 64 (64.0) 0.041 Donor, male 63 (67.0) 60 (60.0) 0.371 Age Patient, y, median 27 38 0.055 Donor, y, median 38 39 0.364 Hematologic malignances, n (%) Acute leukemia 72 (76.6) 61 (61.0) MDS 3 (3.2) 21 (21.0) 0.000 CML 5 (5.3) 10 (10.0) Lymphoma 14 (14.9) 8 (8.0) Status of disease, n (%) 0.000 CR1 42 (44.7) 76 (76) CR2 14 (14.9) 5 (5) NR/beyond CR2 38 (40.4) 19 (19) Time to transplant (d) 361 299 0.946 Conditioning Regimen, n (%) 0.354 BuCy 60 (63.8) 66 (66.0) TBIcy 28 (29.8) 23 (23.0) FB 6 (6.4) 11 (11.0) CD34+ in graft (106/kg) 5.86 4.77 0.057 ≥4.60 51 (54.3) 41 (41.0) 0.084 Disclosures No relevant conflicts of interest to declare.

KIR Ligand Incompatibility in HLA-Identical Sibling Nonmyeloablative Hematopoietic Stem Cell Transplantation for Hematologic Malignancies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5371-5371
Author(s):  
Jae H. Park ◽  
Andrew J. Yee ◽  
Thomas R. Spitzer ◽  
Susan L. Saidman ◽  
David T. Ting ◽  
...  
Keyword(s):  
Stem Cell ◽  
Nk Cell ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
High Incidence ◽  
Matched Sibling ◽  
Donor Sample

Abstract Natural killer (NK) cell alloreactivity based on inhibitory killer immunoglobulin-like receptor (KIR)-ligand incompatibility (i.e., missing KIR ligand) in the graft-vs-host (GVH) direction has been described to favorably influence engraftment, GVHD, and graft-vs-tumor (GVT) effect following haploidentical or matched unrelated HSCT in patients with hematologic malignancies. The degree and effect of KIR-ligand incompatibility has recently been explored following HLA-identical sibling HSCT (Hsu et al., Blood2005;105:4878). Based on a murine model, we developed a clinical trial with a goal of deliberately inducing a GVHD-free mixed chimeric platform following nonmyeloablative conditioning (consisting of equine ATG, cyclophosphamide, thymic irradiation, and a brief course of cyclosporine) and HLA-matched sibling HSCT. Donor leukocyte infusions (DLI) were given as early as five weeks post-HSCT to patients without GVHD in an attempt to achieve a conversion to full donor chimerism (FDC) with the goal of fully capturing GVT effect with little or no GVHD. In this study we hypothesized that KIR-ligand incompatibility in the GVH direction and KIR-ligand compatibility in the host-vs-graft (HVG) direction would reduce the rate of graft failure, decrease the incidence of GVHD, and improve overall survival following HLA-matched sibling HSCT. Fourteen transplant recipients (bone marrow, n=9; peripheral blood stem cell, n=5) with refractory hematologic malignancies (NHL, n=7; HD, n=3; MM, n=2; CLL, n=1; AML, n=1) were analyzed. KIR typing was accomplished using PCR amplified DNA from both donor and recipient patient samples. Typing of the amplified DNA was performed using the Lifecodes KIR-SSO typing kits (Tepnel Lifecodes Corporation). By using the SSO (sequence-specific oligonucleotides) technology in conjunction with the Luminex Instrument, KIR loci were identified for each patient and donor sample. KIR-ligand (HLA) incompatibility in the GVH and HVG directions were assessed based on HLA and KIR genotyping (KIR2DL1, KIR2DL2, KIR2DL3 and KIR3DL1) of 14 donors and 12 of the 14 recipients. Six of the 14 patients eventually lost their grafts despite DLI. Seven patients spontaneously achieved FDC and one converted to FDC following DLI. The missing KIR ligand analysis showed 12 patients (86%, n=12/14) with KIR-ligand incompatibility in the GVH direction (1 missing ligand, n=9; 2 missing ligands, n=3) and 10 patients (83%, n=10/12) with KIR-ligand incompatibility in the HVG direction (1 missing ligand, n=9; 2 missing ligands n=1). The presence or the degree of KIR-ligand incompatibility in GVH or HVG direction was not found to be predictive of spontaneous FDC or graft rejection. There was no significant relationship between the number of missing KIR ligands in either direction and the development of acute or chronic GVHD. This study shows a higher rate of KIR-ligand incompatibility in the GVH (86%) and HVG (83%) directions in the setting of HLA-matched sibling HSCT than previously reported. Although the small number of patients does not allow for statistically meaningful conclusions regarding clinical outcome, the observation of a high incidence of KIR-ligand incompatibility in this population justifies the study of larger patient cohorts to determine the influence of NK cell alloreactivity on transplant outcomes.

Oral Mucositis (OM) and Outcomes of Allogeneic (AL) Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Hematologic Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3126-3126
Author(s):  
Montserrat Vera-Llonch ◽  
Gerry Oster ◽  
Colleen Ford ◽  
John Lu ◽  
Irina Khazanov ◽  
...  
Keyword(s):  
Linear Trend ◽  
Retrospective Chart Review ◽  
Hematologic Malignancies ◽  
Economic Outcomes ◽  
Study Cohort ◽  
Hematopoietic Stem ◽  
Academic Center ◽  
Unrelated Donors ◽  
Report Data ◽  
Total Body

Abstract Background. OM is a common toxicity of conditioning regimens for HSCT that has been associated with adverse clinical and economic outcomes. Methods. A retrospective chart review study of ~400 consecutive HSCT recipients with hematologic malignancies was undertaken at a single academic center. OM severity was assessed across eight oropharyngeal sites using a validated scale which was scored as follows: no erythema/ulceration = 0; erythema only = I; ulceration one site = II; two sites = III; three sites= IV; and four or more sites = V. OM assessments began on the day of conditioning and continued bi-weekly until hospital discharge. Outcomes of interest included number of days of fever, total parenteral nutrition (TPN), and parenteral narcotic therapy, incidence of Grade III or IV (Common Toxicity Criteria) infection, and inpatient days and charges. We report data here for the 281 AL HSCT recipients in the study cohort. Results. Mean age was 41 yrs. Most common diagnoses were acute (33%) and chronic (19%) myeloid leukemia. Most patients (96%) received total body irradiation. Fifty-one percent of grafts were from unrelated donors. Seventy-six percent of patients experienced OM ≥ grade II. The relationship between worst recorded grade of OM and each of the outcomes of interest is reported below. Conclusions. OM is associated with worse clinical and economic outcomes in patients with hematologic malignancies undergoing AL HSCT. Outcomes of AL HSCT in patients with hematologic malignancies, by worst recorded grade of OM Worst Grade of OM (N=281) 0 I II III IV V Outcome n=34 n=33 n=70 n=60 n=43 n=41 -value p *mean, SD; **test for linear trend; Cochran-Armitage for dichotomous measures, GLM for continuous measures Fever days* 3.1 (3.0) 4.8 (4.4) 5.3 (4.9) 5.7 (4.7) 5.9 (4.7) 7.3 (4.6) <0.001 TPN days* 6.7 (7.2) 7.7 (7.8) 8.8 (7.8) 10.2 (7.8) 13.2 (7.2) 14.0 (6.2) <0.001 Narcotic days* 7.6 (6.3) 10.8 (5.0) 10.7 (7.4) 11.5 (5.1) 14.0 (6.8) 17.2 (5.0) <0.001 Infection (%) 85.3 90.9 92.9 93.3 100.0 100.0 0.002 Mortality (%) 8.8 3.0 8.6 15.0 7.0 22.0 0.042 Inpatient days* 28.1 (8.8) 30.3 (10.6) 34.5 (15.1) 32.7 (14.5) 35.9 (10.4) 42.4 (15.1) <0.001 Inpatient charges* (x 1,000 USD) 214 (102) 252 (156) 313 (251) 280 (198) 305 (140) 437 (233) <0.001

Fludarabine, Cytarabine, Busulphan, and Cyclophosphamide (FABC) as Conditioning Regimen in Hematopoietic Stem Cell Transplantation for Treatment of 92 Patients with Hematologic Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1147-1147
Author(s):  
Jianyu Weng ◽  
Xin Du ◽  
Suijin Wu ◽  
Zesheng Lu ◽  
Chengwei Luo ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Chronic Myelomonocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
Myelomonocytic Leukemia ◽  
Related Mortality

Abstract Abstract 1147 Poster Board I-169 In the past twenty years, allogeneic hematopoietic stem cells transplantation (Allo-HSCT) has been accepted as the most effective treatment for many hematologic malignancies. However, the successful rate of allo-HSCT has been limited by transplantation-related mortality and malignancies relapse, no matter using traditional intensity conditioning or reduced-intensity conditioning. In this study, we presented ninety-two patients with hematopoietic malignancies received fludarabine combinasion with modified Bu/Cy (FABC) conditioning regimen before allogeneic hematopoietic stem cell transplantation. Ninety-two patients with hematological malignancies (58 males, 34 females) ranged in age from 14 to 50 (median 28) years. These patients were diagnosed with acute lymphoblastic leukemia (ALL, n=30), acute myelogenous leukemia(AML, n=24), chronic myelogenous leukemia (CML, n=33; CP, n=27; CML-AP, n=5; CML-BC, n=1), myelodysplastic syndrome ( MDS, n=3), chronic myelomonocytic leukemia (CMML, n=1), and one patient coexisted chronic myelomonocytic leukemia and T lymphoblast cell lymphoma. Fifty-five (59.8%) patients were at high risk. From June 2004 to October 2008, 92 patients gave their informed consent and received conditioning regimen with fludarabine-based modified Bu/Cy (FABC conditioning regimen) in allo-HSCT. The FABC regimen consist of cytarabine 2.0 g/ m2 on day -9, busulphan (Bu) 3.2 mg/kg per day for intravenous on days -8 to day-6, followed by cyclophosphamide (Cy) 60 mg/kg per day on days -5 and day-4, combined fludarabin 30 mg/m2 per day for three consecutive days, on days -6 to day-4, and Me-CCNU (1-(2-Chloroethyl)-3-(4-ethylnitrobiphenyl Cylohexyl4)-1- Nitrosourea) 250 mg/m2 on day -3. Graft-versus-host-disease(GVHD) prophylaxis consisted of cyclosporine A, short-term MTX and Mycophenolate Mofefil (MMF 1.0g/day, on d-8 to d-1). Anti-T-lymphocyte globulin (2.5 mg·kg-1·d -1, on d-3 to d-1) was added to patients with mismatched sibling or unrelated donors. Follow-up was performed on 30 December, 2008. Ninety-two patients engrafted successfully, the median time for ANC >0.5×109/L was 12 (8 to 22) days, and for BPC > 20×109/L was 12 (7 -32) days. Detected by short tandem repeat (STR)-PCR, complete donor chimerism was comfirmed in all patients on day +21 or day+30. The incidence of acute GVHD was 25% (23/92), and grades 3 to 4 acute GVHD developed in 8 (8.7%) of 92 patients with in 100 days after HSCT. Chronic GVHD developed in 40(47.6%) of 84 patients who were alive more than 100 days after HSCT, and the incidence of extensive cGVHD was 35.7%(30/84). The transplant related mortality (TRM) was 19.6% (18/92), mainly from severe infection (n=7), acute or chronic GVHD (n=5), transplant associated-microangiopathy (n=2), diffusion alveolar hemorrhage (n=2), and post-transplant lymphoproliferative disorders (n=2). With a median follow-up of 16.2(1.5 to 54.5) months, 70 (76.1%) of the 92 patients were alive and 67(72.8%) were disease-free. The probabilities of OS at 1 year and 2 years was 80% and 72.5%, and DFS was 79.1% and 71.4%, respectively. These results suggest that the fludarabine-based modified Bu/Cy conditioning regimen (FABC) should reduce severe acute GVHD and accelerate hematopoietis resconsition without increasing chronic GVHD and lower leukemia relapse rates even in high-risk patients. Footnotes Corresponding author Disclosure No relevant conflicts of interest to declare.

No Disadvantage in Outcome of Using Matched Unrelated Donors as Compared With Matched Sibling Donors for Bone Marrow Transplantation in Children With Acute Lymphoblastic Leukemia in Second Remission

2001 ◽  
Vol 19 (14) ◽  
pp. 3406-3414 ◽  
Author(s):  
Ulla M. Saarinen-Pihkala ◽  
Göran Gustafsson ◽  
Olle Ringdén ◽  
Carsten Heilmann ◽  
Anders Glomstein ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Total Body Irradiation ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Antilymphocyte Globulin ◽  
Unrelated Donors ◽  
Matched Sibling ◽  
Total Body

PURPOSE: We evaluated the outcome of children with acute lymphoblastic leukemia (ALL) in second remission (2CR), comparing bone marrow transplantation (BMT) using either matched sibling donors or unrelated donors (URDs). PATIENTS AND METHODS: A total of 65 patients, aged 2 months to 20 years at BMT, with ALL in 2CR underwent allogeneic BMT at seven Nordic centers during 1990 to 1997. Of the first relapses, 85% were in bone marrow; 46% occurred on therapy, and 54%, off therapy. The preparative regimens were cyclophosphamide plus total-body irradiation ± antithymocyte/antilymphocyte globulin, busulfan plus cyclophosphamide ± antithymocyte/antilymphocyte globulin, or cytarabine plus total-body irradiation. Of the allografts, 37 were from HLA-matched siblings and 28 were from URDs. RESULTS: In the sibling versus URD graft recipient groups, the posttransplantation 5-year event-free survival was 39% versus 54% (P = .4), the estimated posttransplantation relapse rate was 76% versus 40% (P = not significant [NS]), and the toxic death rate was 19% versus 11% (P = NS). The incidence of significant (grade 2 to 4) acute graft-versus-host disease (GVHD) was 38% versus 64% (P < .05) and was 14% versus 32% (P < .10) for severe (grade 3 to 4) acute GVHD; the incidence of chronic GVHD was 26% versus 57% (P < .05) and was 13% versus 22% (P = NS) for extensive chronic GVHD in the sibling and URD groups. CONCLUSION: BMT with matched URD allografts offers at least equal survival for children with ALL in 2CR, as compared with allografts from matched sibling donors. URD allografts were not associated with a higher toxic mortality rate, although both acute and chronic GVHD were more frequent with URD. Indications for using matched URD allografts in ALL 2CR can be considered the same as for using matched sibling donors.

Outcomes Analysis of Patients Surviving ≥2 Years after Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2762-2762
Author(s):  
Ronald Sobecks ◽  
Matt Kalaycio ◽  
Brad Pohlman ◽  
Steven Andresen ◽  
Lisa Rybicki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Survival Curve ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Myeloid Malignancies ◽  
Lymphoid Malignancies ◽  
Matched Sibling ◽  
Donor Transplant

Abstract We have previously demonstrated the value of evaluating patients with NHL undergoing autologous HSCT at 2 years post-transplant; high grade lymphoma patients in CCR 2 years post-transplant are cured, whereas patients with intermediate and low grade histologies are at ongoing risk of relapse. We elected to perform a similar analysis of AHSCT patients. We retrospectively reviewed 161 consecutive AHSCT recipients who had a minimum of 2 years follow-up and who were alive 2 years post AHSCT. Patients received their transplants from 7/1988 to 7/2002. Median age was 36 years; 75% had myeloid malignancies and 25% lymphoid; AML was the most common diagnosis (39%) followed by CML (29%), ALL (14%), NHL (10%), MDS (6%), and myeloma (2%). 98% received bone marrow alone as the hematopoietic stem cell source; 98% received a busulfan/cyclophosphamide-based preparative regimen. 129 (80%) had a matched related donor. Of those patients alive 2 years post AHSCT, 31 patients (19%) have subsequently died, with a median follow up of 6 years. Relapse was the cause of death in 29%; GVHD in 35%; secondary malignancy in 7%; infections in 16%. Patients with myeloid malignancies faired better than those transplanted with lymphoid malignancies, as shown below; (p= 0.04) Figure Figure When we analyzed the pts who developed their first episode of any chronic GVHD or extensive chronic GVHD there were no significant differences between lymphoid and myeloid malignacy patients. Patients receiving a matched sibling donor transplant did not have a plateau in their survival curve, and it continued to inexorably decline. Patients receiving a matched unrelated donor transplant did have a plateau of their survival curve if patients survived at least 3 years (p=0.03). We conclude that the significant majority of patients alive after AHSCT do well with extended follow-up. The graft vs. tumor effect appears to be more robust in myeloid malignancies as compared to lymphoid malignancies. Although most of these patients do well with extended follow-up, the lack of a plateau in the survival curve for patients receiving a matched sibling donor allogeneic BMT warrants additional study.

Stem Cell Transplantation from HLA-Identical Siblings Versus Alternative Donors in β-Thalassemia Diseases.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3157-3157
Author(s):  
Preeda Vanichsetakul ◽  
Panya Seksarn ◽  
Issarang Nuchprayoon
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Thalassemia Major ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Matched Sibling

Abstract Background: Allogeneic hematopoietic stem cell transplantation (SCT) has been established as a curative therapy for β-thalassemia major which is prevalent among Thais. Donors are usually patients’ siblings but the chance to find an optimal HLA-identical is just about 30%. Thus clinical trial using alternative donors such as partially-mismatched related donors or matched unrelated donors could be a good choice. Methods: To study the efficacy and results, we retrospectively review our experience with β-thalassemia pediatric patients undergoing transplantation from July 1999 to July 2006. Results: There were 43 patients categorized into HLA-identical siblings group (n=26, 13 male and 13 female) and alternative donors group (n=17, 14 male and 3 female). Median age and weight were 7.2 years (1.2–14.8 years), 19.8 kg (9.8–34 kg) and 7.7 years (1.4–14.8 years), 21.5 kg (11–33 kg), respectively. Amongst 26 matched siblings there were 17 bone marrow (BM), 4 peripheral blood stem cell (PBSC), and 5 cord blood (CB) donors. Of the alternative group stem cells derived from 12 matched unrelated, 2 two-antigen mismatched sibling CB, 2 one-antigen mismatched unrelated CB, and 1 one-allele mismatched unrelated BM donors. Myeloablative conditioning regimen consisted of busulfan (oral or intravenous) and cyclophosphamide for matched siblings SCT. Anti-thymocyte globulin was added for alternative donors SCT. Fludarabine was also used in addition for unrelated donors SCT. Graft-vs-host disease (GvHD) prophylaxis consisted of cyclosporine plus methotrexate except for unrelated SCT that tacrolimus plus methotrexate were used instead. Median numbers of infused CD34+ cells of the matched siblings group were 11.1x106/kg (3.7–35.4) in BMT (n=17), 9.3x106/kg (7.1–12.8) in PBSCT (n=4), and 0.94x105/kg (0.2–5.3) in CBT (n=5), compared to 5.5x106/kg (1.5–18.1) in BMT (n=10), 11.1x106/kg (11–17.2) in PBSCT (n=3), and 2.1x105/kg (1.5–3) in CBT (n=4) of the alternative group. Median times to neutrophil and platelet engraftments in each groups were 15 and 33 days, compared to 17 and 41 days, respectively. 39 successful donor engraftments were achieved from 38 HLA-matched (25 related and 13 unrelated) donors and from 1 mismatched unrelated CB unit. The remaining 1 of the matched related group and 3 of the alternative group did not engrafted, all but one case subsequently resumed autologous recovery. Acute GvHD occurred in 4 matched-sibling and 5 unrelated SCT recipients. After immunosuppressive therapy the lesions were completely resolved in all but two patients, one who suffered from severe grade IV intestinal GvHD and another who later developed extensive chronic GvHD which required treatment longer than 4 years. There were 4 mortalities only in the alternative group: 3 patients died post-engraftment due to severe fatal GvHD (n=1), cerebral aspergillosis (n=1), severe veno-occlusive disease with liver failure (n=1; Pesaro class 3); and one died from neutropenic sepsis 3-week after 4/6 matched related CBT. Median follow-up time for surviving patients was 53.5 months (2–84 months). Overall and disease-free survival in HLA-matched SCT (n=38) recipients were 94.7% (n=36) and 92.1% (n=35), compared to in HLA-mismatched (n=5) 60% (n=3) and 20% (n=1), respectively. Conclusions: SCT for β-thalassemia major using HLA-matched donors, either related or unrelated, had superior results than HLA-mismatched. In situation of unavailable matched sibling donors, the search for an appropriate complete HLA-matched unrelated volunteer donor using high resolution DNA typing is essential for favorable outcomes.

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