scholarly journals Favorable Outcome of Sequential HLA-Haploidentical Transplantation Using Ptcy As GvHD Prophylaxis in High Risk AML and MDS of the Elderly

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3458-3458
Author(s):  
Alessia Fraccaroli ◽  
Dusan Prevalsek ◽  
Sarah Elena Häbe ◽  
Veit Bücklein ◽  
Christoph Schulz ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
The Elderly ◽  
High Dose ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Therapeutic Concept ◽  
Haploidentical Transplantation

Abstract Sequential conditioning regimens, comprising cytoreductive chemotherapy shortly applied prior to reduced intensity conditioning are successfully used for high-risk (HR) AML/MDS in matched related and unrelated donor hematopoietic stem cell transplantation. However, few data are available for sequential conditioning in the context of HLA-haploidentical transplantation (haplo-HSCT), especially in the elderly. To investigate the relative merits of sequential haplo-HSCT in the elderly we retrospectively analyzed the outcome of thirty-five patients (pts) with advanced AML/MDS (>=50 years old). Thirty-three pts suffering from HR AML, defined by refractory, relapsed or secondary leukemia, or complete remission with adverse-risk genetics according to ELN criteria and two pts with HR MDS according to IPSS-R, who underwent T-cell-replete haplo-HSCT at our institution between January 2009 and November 2016 were included. Disease was active in 29 pts while 6 had achieved CR. Pre-transplantation risk factors were scored using the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) which was ≥3 in 13 pts (median HCT-CI:2, range 0-8). A sequential therapeutic concept using either FLAMSA (n=26) or clofarabine (n=9) for cytoreduction was used prior to RIC in all pts. Bone marrow (54%) and peripheral blood stem cells (46%) were both used as graft source. Post-grafting immunosuppression consisted of high-dose cyclophosphamide, tacrolimus and MMF in all pts. Median age was 60 years (50-70). One graft rejection occurred. Three pts died early in aplasia. Neutrophil and platelet engraftment was achieved in 95% and 77% of evaluable pts, respectively at a median of 16,5 (13-89) and 31,5 (11-103) days.Acute GvHD grade I-III occurred in 25/32 of the pts (grade III n=2); no patient developed grade IV aGvHD. Chronic GvHD was observed in 13/29 pts and was most frequently assessed as mild (n=6) or moderate (n=5) while 2 pts developed severe cGvHD. No GvHD related death was observed. CI of NRM at day 100, 1-year and 3-years was 11%, 23% and 23%, respectively. CI of relapse at 1- and 3-years was 15% and 27%, with a median time to relapse of 152 days (20-413). At a median follow up of 27 months (4-74), estimated one- and three-year overall survival (OS) was 62% and 52% respectively. One- and three-year leukemia-free survival (LFS) was 59% and 52%. Our results suggest that using a sequential therapeutic concept in PTCY-based haplo-HSCT is safe and properly tolerated while it provides a favorable disease control when treating elderly HR MDS/AML pts. Thus, sequential haplo-HSCT seems to be a valuable alternative in pts who lack a conventional donor or are in urgent need for prompt transplantation. Disclosures Tischer: Jazz Pharmaceuticals: Other: Jazz Advisory Board.

Fludarabine, Amsacrine, High-Dose Cytarabine and Total Body Irridation Followed by Allogeneic Stem Cell Transplantation for the Treatment of High Risk or Relapsed Acute Lymphoblastic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5086-5086
Author(s):  
Fabian Zohren ◽  
Thorsten Graef ◽  
Ingmar Bruns ◽  
Akos Czibere ◽  
Fenk Roland ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Good Condition ◽  
White Blood Count ◽  
High Dose ◽  
Unrelated Donor ◽  
Grade Iii

Abstract In this prospective study we examined the use of an intensified conditioning regimen followed by allogeneic blood-stem-cell transplantation (BSCT) for the treatment of young adults in physically good condition with relapsed or high risk acute lymphoblastic leukaemia (ALL). Eleven patients with ALL received FLAMSA chemotherapy (fludarabine 30mg/m2 - cytarabine 2000mg/m2 -amsacrine 100 mg/m2 on day −10, − 9, − 8and −7), Anti-Thymocyte-Globulin (ATG 20 mg/kg BW on day −6, −5 and −4) and fractionated TBI (2 x 2 Gy on day −3, − 2 and −1) followed by matched unrelated donor (n=10) or matched sibling donor (n=1) SCT. The principle reasons for high risk stratification were refractory disease during first-line induction therapy (6, 55%), relapse (2, 18%), extramedullary disease manifestation (1, 9%), ALL subtype (6, 55%), unfavorable cytogenetics (5, 45%) and white blood count >30000 μL at time of diagnosis (3, 27%). After a median follow-up time of 604 days (range 202 – 1042 days) 8 patients (73%) are alive and 3 patients (27%) died. The median overall survival was not reached. Two patients died after relapse on days +121 and +449, another patient died from treatment related complications (HUS-TTP) on day +87. One patient relapsed on day +200 and is currently alive, the remaining 7 patients are alive and free of desease. Treatment related toxicities were acceptable. With 6 out of 11 patients developing grade III/IV infections during neutropenia, infectious complications remained of major importance. Other non-haematological side effects seen within this group of patients were less frequent and almost exclusively limited to gastrointestinal toxicities. Five patients (45%) had grade III/IV mucositis and 5 patients (45%) had grade III/IV nausea, while 4 patients (36%) showed grade III/IV diarrhoea. There was no case of acute toxicity related to the cardiavascular or central nervous system. The incidence of acute GvHD (aGvHD) was 36% (n = 4) and limited to grades II-III. Eight patients were evaluable for chronic GvHD (cGvHD). Out of those 4 patients (36%) developed cGvHD (3 limited disease, 1 extensive disease). We conclude that allogeneic transplatation after the FLAMSA-ATG-TBI regimen is feasible and provides effective therapy for this group of high-risk patients.

scholarly journals Killer Cell Immunoglobulin-like Receptor Ligand Matching Determines the Post-Transplant High Risk Groups Among Patients with Permissive HLA Mismatch in Unrelated Donor Hematopoietic Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4566-4566
Author(s):  
Yoo Jin Lee ◽  
Joon Ho Moon ◽  
In Hee Lee ◽  
Jae-Ho Yoon ◽  
Byung-Sik Cho ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Killer Cell ◽  
Risk Groups ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Peripheral Blood Stem Cells

Abstract Background: Human leukocyte antigen (HLA) matching between donor and recipient is a key part of successful allogeneic hematopoietic cell transplantation (allo-HCT). The HCT from the unrelated donor (UD) with one allele/antigen mismatch (MM) can be as beneficial as HCT from perfectly matched donor. For the remaining patients, the donors with permissive mismatches may be the option. In HLA-mismatched transplantation, the patient and donor can also be mismatched for their killer cell immunoglobulin-like receptor (KIR) ligands that recognize allotypic determinants shared by certain HLA class I allele groups. Recent research has accumulated evidence of the role of each HLA locus and KIR ligand MM on clinical outcomes for UD-HCT. However, HCT outcomes of the patients with permissive MM depending on KIR ligand MM (KIR-L-MM) status remain obscure in UD-HCT. In the current study, we identified permissive and nonpermissive MM allele combinations and analyzed the effects of these mismatches in combination of KIR ligand mismatches in patients with acute myeloid leukemia (AML). Methods: A total of 438 patients with AML who underwent allo-HCT from UD from 2007 to 2014 were analyzed. Alleles of patients and donors at the HLA-A, -B, -C, and -DRB1 loci were identified by the high resolution DNA typing. Nonpermissive HLA allele combinations were defined as a significant HLA risk factor for severe acute graft-versus-host disease (aGVHD). KIR-L-MM among patient-donor pairs were searched in the Immuno Polymorphism Database available at www.ebi.ac.uk/ipd/kir. Results: Median age of the patients was 45 (range 15-60) years and 117 patients (40.4%) were female. Eighty-five (19.4%) patients were high risk at the time of HCT. Reduced intensity conditioning was performed in 131 patients (29.9%) and anti-thymocyte globulin was used in 324 patients (74.0%). Primary graft source was peripheral blood stem cells (n=369, 84.2%) and median 6.0 x 106/kg cells were infused. Severe aGVDH occurred in 43 patients (9.8%) and chronic GVHD (cGVHD) in 193 (44.1%). With median follow-up duration of 19 (range, 2-96) months, treatment-related mortality (TRM) occurred in 111 patients (25.3%), relapse in 119 (27.2%) and death in 214 (48.9%). Two-hundred sixty-four patients (60.3%) were HLA full matched in the 4 loci. Mismatches in HLA-A loci observed in 64 patients, HLA-B in 35, HLA-C in 98, and HLA-DRB1 in 60. Five nonpermissive MM pairs in 33 patients were identified as donor/patient pair: A*02:06/A*02:01, C*03:03/C*08:01, C*08:01/C03:04, C*08:01/C*15:02, and DRB1*04:03/DRB1*04:05. Among 98 patients with HLA-C loci MM, 16 patients showed KIR ligand MM (KIR-L-MM) as GvH direction, which was observed in the permissive MM group. Severe aGVHD occurred in 30.4%, 22.4%, 13.4%, and 10.8% in nonpermissive, permissive MM and KIR-L-MM, permissive MM and KIR-L-M, and full match group, respectively (p=0.003). The 3-year overall survival (OS) rate was inferior in permissive MM and KIR-L-MM group (30.0%) compared to full match (53.5%), permissive MM and KIR-L-M (51.8%), and nonpermissive (42.4%) group (p=0.067). The 3-year TRM was higher in permissive MM and KIR-L-MM group (57.5%) than full match (21.0%), permissive MM and KIR-L-M (27.7%), and nonpermissive (33.3%) group (p=0.006). In the multivariate analysis, high risk at HCT (HR 2.087, p<0.001), severe aGVHD (HR 3.851, p<0.001), and cGVHD (HR 0.321, p<0.001) were identified as variables affecting the OS. The following variables adversely affected on TRM: permissive MM and KIR-L-MM group (HR 2.699, p=0.007), severe aGVDH (HR 2.204, p=0.001), and cGVHD (HR 2.052, p<0.001). Non-permissive MM (HR 7.487, p=0.001) and CD34+ cells >6x106/kg (HR 4.113, p=0.017) were high risk factors on severe aGVHD. Conclusion: Permissive MM for HLA could be further classified into high risk groups with regard to TRM by KIR-L matching in UD-HCT. The evaluation of KIR-L matching is warranted to reduce unfavorable outcomes among the patients with permissive MM in UD-HCT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Haploidentical Transplantation (HAPLO) with Post-Transplant High-Dose Cyclophosphamide for Graft Vs Host Disease (GVHD) Prevention in the Treatment of High Risk Hematological Neoplasms

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4545-4545
Author(s):  
Jorge Gayoso ◽  
Mi Kwon ◽  
David Serrano ◽  
Pascual Balsalobre ◽  
Javier Anguita ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
High Dose ◽  
Unrelated Donor ◽  
Haploidentical Transplantation ◽  
Gvhd Prophylaxis

Abstract Abstract 4545 Introduction: Allogeneic transplantation is the only curative option in the treatment of multiple high risk hematologic neoplasms. Only 25–30% of patients have an HLA identical sibling donor and searching for a compatible unrelated donor or cord blood renders satisfactory results in around 60–70%. Haploidentical transplantation (HAPLO) offers a therapeutic alternative to more than 95% of such patients with the advantages of quick availability, easy programming and a committed donor. Patients and Methods: We evaluate the results of HAPLO with a reduced intensity conditioning regimen (Fludarabine 30 mg/m2 ×5 days (-6 to -2), Cyclophosphamide 14,5 mg/kg ×2 days (-6 and -5), IV Busulfan 3,2 mg/kg × 1–3 days (BUX, days -4 to -2) employing high doses of Cyclophosphamide post graft infussion (50 mg/kg days +3 and +4) as GVHD prophylaxis together with standard doses of cyclosporine and mycophenolate from day +5. Results: From Dec-2007, we have done 26 HAPLO in 4 spanish centers. Median age was 38 years (16–57), 20 were male and all were in advanced phases of their diseases (12 Hodgkin′s, 6 AML, 3 ALL, 2 MM, 1 MDS, 1 MF y 1 NHL). Previous autologous HSCT has been employed in 13 and allogeneic HSCT in 6 (2 MURD and 4 UCB). Disease status at HAPLO was CR in 8, PR in 14 and refractory in 4. Bone marrow was used in 16 and unmodified peripheral blood in 10. The haploidentical donor was patient′s mother (8), father (3), siblings (11) or other relatives (4). BUX was used in 1 dose (15), 2 doses (8) or 3 doses (2) and TBI 200 cGy in 1 case. Mean neutrophils engraftment was achieved on day +18 (13–26) and platelets >50K on day +27 (17–150) in all but 2 cases of graft failure (7.7%) due to progression (MF) or relapse (M7-AML). Main toxicities were grade 1–2 mucositis in 50%, febrile neutropenia in 75% and CMV reactivations in 58% with a 100 days NRM of 3.8% (1/26, VOD and MOF) and 10% NRM at 6 months (2/20). Grade II-IV acute GVHD appeared in 10/23 patients at risk (43%) and grade III-IV in 4/23 (17%). Chronic GVHD affected to 4/15 (27%), being extensive in 1/15 (6.7%). With a median follow-up of 9 months (1–38), 13/22 (59%) are alive in CR, progression or relapse has ocurred in 6/24 (25%). Immune reconstitution seems fast and complete in those evaluated. Conclusions: HAPLO with high-dose cyclophosphamide as GVHD prophylaxis is a useful alternative in the treatment of high risk hematologic tumours, with low toxicity, acceptable GVHD incidence and severity, long lasting remissions, and fast immunological reconstitution. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Cell Transplantation in AML: Comparable Results After Matched or Mismatched Unrelated Versus Matched Related Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1199-1199 ◽  
Author(s):  
Birgit Federmann ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
Wolfgang Andreas Bethge
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Off Label Use ◽  
Hematopoietic Stem ◽  
Off Label ◽  
Significant Difference ◽  
Label Use

Abstract Abstract 1199 Poster Board I-221 Currently, most treatment algorithms reserve the use of allogeneic hematopoietic stem cell transplantation (HCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR) to patients with a matched related donor (MRD) and intermediate/high-risk disease. However, the role of HCT from a matched or mismatched unrelated donor (MUD/MMUD) in patients with AML remains to be defined. We retrospectively analyzed a cohort of 219 consecutive adult patients (98 female, 121 male) with AML who received HCT from 2000-2009 at our institution. The patients were transplanted after either myeloablative (MAC, n=139) or dose-reduced-conditioning regimens (RIC, n=80). Median age of patients was 50 years (range, 18-76). 77 patients were transplanted from MRD, 80 patients from MUD and 62 patients from MMUD (one antigen mismatch (MM)=31; two antigen MM=2; one allel MM=24; two allel MM=3, one antigen/one allel MM= 2). In all but six patients receiving MMUD grafts, ATG was included in the conditioning. Age, risk profile and pretreatment were evenly distributed among the three cohorts of patients. At time of HCT 22 (MRD), 18 (MUD) and 28 (MMUD) patients were not in CR. Current overall survival is 40 of 77 (52%) in patients transplanted from MRD, 48 of 80 (60%) from MUD and 34 of 62 (55%) from MMUD with a median follow-up of 1309 (range, 98-3173), 796 (range, 87-3075) and 648 (range, 111-1973) days of alive patients, respectively. Kaplan-Meier-estimated 3-year overall survival (OS) was similar with 54% after MRD-, 56% after MUD- and 46% after MMUD-HCT (p=0.4554). In patients transplanted in CR, 3-year estimated OS was also comparable (64% MRD vs. 58% MUD vs. 55% MMUD, p=0.6614). However, in patients transplanted in partial remission (PR) we observed a trend for a better survival in patients receiving a MUD graft (30% MRD vs. 46% MUD vs. 39% MMUD, p=0.1707). In the patients receiving MAC we observed a better OS compared to RIC with an estimated 3-year OS of 58% vs. 38% (p=0.1047) mainly due to a lower incidence of relapse. In the subgroup of patients receiving MRD-HCT this survival benefit was significant (61% vs. 21%, p= 0.0327) while there was only a trend for MUD- or MMUD-HCT (60% vs 45%, p=0.5702 and 49% vs. 43%, p= 0.7566, respectively). There was no significant difference in the incidence of acute GvHD >II with 25% (MRD), 35% (MUD) and 34% (MMUD) or chronic GvHD with 43% (MRD), 46% (MUD) and 34% (MMUD), respectively. A significant better survival of patients with limited cGvHD vs. extensive or without cGvHD (estimated 3-year OS 73% vs. 34% vs. 47%, p=0.0001) was observed. This advantage was present in all subgroups with a significant better survival in the group with MRD (86% vs. 38% p= 0.0034), a trend in MUD (67% vs. 55% p= 0.0564) and MMUD (59% vs. 55%, p= 0.3111). No significant influence on survival or GVHD of the degree and loci of HLA-mismatch could be detected. In conclusion in our cohort of patients, HCT from MUD or MMUD in AML resulted in a similar outcome compared to MRD. In patients with PR at time of HCT, the use of MUD and occurrence of limited cGVHD may lead to improved survival due to an enhanced graft-versus-leukemia-effect. Disclosures: Off Label Use: some chemotherapeutical agents in the conditioning are off-label-use.

Thiotepa-Based Vs TBI-Based Myeloablative Conditioning Prior To Allogeneic Stem Cell Transplantation (HSCT) For Acute Myeloid Leukemia (AML) In First Complete Remission (CR1): A Retrospective Analysis From The ALWP Of The EBMT

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2123-2123 ◽  
Author(s):  
Sandra Eder ◽  
Myriam Labopin ◽  
William Arcese ◽  
Reuven Or ◽  
Ignazio Majolino ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
High Dose ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Secondary Aml ◽  
Number Of Patients

Abstract Background Thiotepa (N,N'N'-triethylenethiophosphoramide), which is an alkylating compound, has an antineoplastic activity and has been used in oncology (e.g. breast-, ovarian- and bladder cancer) for decades. In the recent years, and because of its good safety profile, Thiotepa has been increasingly used both for autologous and allogeneic hematopoietic stem cell transplantation conditioning. Interestingly, this agent has a very active myeloablative activity but also its mechanism of action can mimick the effect of radiation. With this background, the aim of this study was to compare outcome of patients receiving a myeloablative conditioning consisting of either high dose TBI or Thiotepa-based chemotherapy. Methods Inclusion criteria were adults with AML, first allograft in CR1 from an HLA-matched sibling donor (MSD) or an unrelated donor (UD) between 2000 and 2011 and myeloablative conditioning. We first compared patient and transplant characteristics between the two types of conditioning, and then performed a pair-matched analysis. Results The number of patients was 2833 in the TBI group and 102 in the Thiotepa group. Patients who received Thiotepa were older (49y vs 40y, p<10-4), transplanted more recently (2009 vs 2006, p<10-4) and later after the diagnosis of AML (183 days vs 143 days, p<10-4). The percentage of secondary AML was also higher in the Thiotepa group (14% vs 6%; p=0.0002). There was no difference regarding patient/donor gender, type of donor and source of stem cells. In this cohort, we were able to match 96 patients who received Thiotepa with 185 patients who received high dose TBI. Matching factors were: age at transplantation (10 years classes), year of transplant, interval from diagnosis to transplant (less or more than median day), secondary AML and type of donor (MSD/UD). The characteristics of the 2 groups are summarized in Table 1. Median dose of TBI was 12 Gy (range, 8-16). In this group, TBI was combined with Cyclophosphamide (84% of cases), Fludarabine (14%) or other compounds (2%). On the other hand, Thiotepa was administered with Cyclophosphamide (45%), Fludarabine (54%) with/without Busulfan and other combinations (1%). Engraftment occurred in 96% of patients using Thiotepa-based conditioning versus 99% after TBI (p=0.11). The interval from transplant to neutrophils count>500/µL was 16 days (range, 9-42) versus 17 days (range, 9-81) in the 2 groups, respectively (p=0.23). Acute GvHD grade II+ was observed in 25 patients (27%) after Thiotepa-containing regimen versus 42 patients (25%) after TBI (p=0.78). 2-years cumulative incidence of chronic GVHD was 48±4% and 41±6% in the 2 groups, respectively (p=0.15). The 2-year cumulative incidences of non-relapse mortality (NRM) was 21±4% versus 27±4% (p=0.57) and relapse incidence (RI) was 18±4% versus 21±3% (p=0.71) in the Thiopeta and TBI groups, respectively. The 2-year leukemia-free survival (LFS) and overall survival (OS) were 61±5% and 64±5% in the Thiotepa group versus 51±4% and 52±4% in the TBI group (LFS: p=0.40; OS: p=0.25). Conclusion This pair-matched analysis suggests that a Thiotepa-based myeloablative conditioning regimen prior to allogeneic HSCT in AML in first CR, can allow achieving similar results to high-dose TBI-based myeloablative conditioning. Also, given the deleterious long term side effects of TBI, it is likely that a Thiotepa-based myeloablative conditioning would represent an attractive and valid alternative to TBI. Prospective trials are currently planned in this setting. Disclosures: Bacigalupo: ADIENNE : Speakers Bureau. Mohty:Riemser : Research Funding.

Hematopoietic Stem-Cell Transplantation from Unrelated Donors in Elderly Patients (> 55 Years): Older Age Is No Longer a Contraindication When Using Reduced Intensity Conditioning.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2750-2750
Author(s):  
Avichai Shimoni ◽  
Nicolaus Kröger ◽  
Tatjana Zabelina ◽  
Frances Ayuk ◽  
Izhar Hardan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
The Elderly ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Reduced Intensity

Abstract Allogeneic stem-cell transplantation (SCT) is a potentially curative approach for patients (pts) with hematologic malignancies. However, it is associated with a high risk of treatment-related complications. Risks are significantly increased with advanced age, concurrent medical problems and with unrelated donors, therefore most centers limit unrelated-donor SCT to pts younger than 50–55 years. Moreover, hematological malignancies are more common and have a worse prognosis in the elderly, thus many pts who could benefit from SCT were often deferred from this potentially curative approach. Reduced-intensity conditioning allowed extension of allogeneic SCT to a wider pt population including the elderly, however there is only limited data on the feasibility and outcome of unrelated-donor SCT in elderly pts over age 55 years. In this study we report our experience with 40 pts over age 55 having unrelated-donor SCT following reduced-intensity conditioning. The median age was 58 years (range, 55–66). Eleven pts were over age 60 years. Diagnoses included AML (n=19; 7 CR1, 9 CR2, 3 refractory; 12 secondary to MDS or prior chemotherapy), MDS (n=4), myelofibrosis (n=2), CML (n=3), multiple myloma (n=8), non-Hodgkin’s lymphoma (n=4). The preparative regimen consisted of fludarabine combined with oral busulfan (8 mg/kg, n=8), intravenous busulfan (busulfex, 6.4 mg/kg, n=15), treosulfan (30 g/m2, n=5) or melphalan (100–150 mg/m2, n=12) and serotherapy, either ATG (n=36) or alemtuzumab (n=4). Thirty-six pts engrafted with a median of 14 days. Four pts died prior to engraftment. With a median follow-up of 14 months (range, 1– 54), 21 pts are alive and 19 have died, 13 of treatment-related causes and 6 of relapse. The probabilities of overall and disease-free survival at 1-year after SCT were 46% (95 CI, 28–63%) and 40% (95 CI, 23–57%), respectively. The cumulative incidence of non-relapse mortality (NRM) and relapse at 1 year were 35% and 25%, respectively. Acute GVHD grade II–IV and chronic GVHD occurred in 36% and 45%, respectively. The status of disease at SCT and the conditioning regimen used were the most significant predictors of outcome. Pts with chemosensitive or untreated malignancy had an OS of 52% whereas pts with refractory malignancy had an OS of 16% (p=0.05). Pts conditioned with fludarabine and busulfex or treosulfan had an OS of 57% compared with 35% in pts conditioned with fludarabine and melphalan or oral busulfan due to increased NRM with the later regimens (p=0.04). Multivariable analysis confirmed the independent impact of these factors with hazard ratios for decreases OS of 3.1 and 3.2, respectively. When a more homogenous subgroup of 23 pts with AML or MDS was analyzed, the 1-yaer OS and DFS were 49% (95 C.I. 24–75%) and 43% (95 C.I. 18–68%), respectively. NRM was 24% (95 C.I. 11–54%). In conclusion, unrelated-donor SCT is feasible in elderly pts, with outcomes that are similar to younger pts. Favorable outcome was observed in pts with myeloid malignancies, and those transplanted in remission and early in the course of disease. The newer regimens containing intravenous busulfan or treosulfan were less toxic translating into better outcome. Age alone should no longer be considered a contraindication to unrelated-donor SCT.

Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

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