Comparable Results of HLA Identical Sibling Donor Peripheral Blood Hematopoietic Stem Cell Transplantation after Reduced-Intensity and High-Dose TBI-Based CD34+-Positive Cell Selection Myeloablative Preparative Regimens for High-Risk Myelodysplasia or Acute Myeloid Leukemia in First Remission: Results from a Prospective Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2995-2995
Author(s):  
Rodrigo Martino ◽  
David Valcarcel ◽  
Jose L. Pinana ◽  
Anna Sureda ◽  
Salut Brunet ◽  
...  
Keyword(s):  
High Risk ◽  
Univariate Analysis ◽  
Normal Karyotype ◽  
Disease Status ◽  
High Dose ◽  
Early Disease ◽  
Hematopoietic Stem ◽  
Poor Risk ◽  
Reduced Intensity

Abstract We prospectively compared the efficacy of allogeneic PBSCT from an HLA-identical sibling in adults with poor-risk AML or MDS in an early disease status (AML or RAEB type 2 in first CR after chemotherapy or RAEB type 1 with poor prognosis). Poor-risk AML/MDS was defined as the presence at diagnosis of one or more of the following: poor-risk karyoype, normal karyotype with flt-3 duplications or MLL mutations, high level of MRD after consolidation (>0.1%), and, in RAEB type 1, an IPSS3Int-2. Based only on the patients’ age, the transplant protocol consisted in conditioning with cyclophosphamide-TBI and use of CD34+-selected PBSCT (CyTBI-CD34+ group, if £ 50 y.o.) or a reduced-intensity conditioning (RIC) with fludarabine and oral busulphan (FluBu-RIC, If > 50 y.o.). Between 1998 and 2005, 74 consecutive patients entered the study (35 in the CyTBI-CD34+ and 39 in the FluBu-RIC group). Both groups differed in some baseline characteristics, mainly younger age in the CyTBI-CD34+ group (median 42 vs. 59 years, p<0.01), a higher transplant comorbidity index in the FluBu-RIC group (median 0 vs. 3 points, respectively, P<0.01), a higher proportion of AML (with respect to RAEB) in CyTBI-CD34+ group (82% vs 54%, respectively, P=0.02), and a higher proportion of poor-risk karyorypes in the FluBu-RIC group (32% vs 72%, respectively, P<0.01). The median follow-up exceeds 4 years in both groups. All patients had sustained donor-engraftment by day +60, except for one lethal graft failure in the CyTBI-CD34+ group. The 4-year probability of OS was and LFS were similar in both groups (52% and 53% in the CyTBI-CD34+ group vs. 53% and 53% in the FluBu-RIC group, respectively, P>0.8 for OS and LFS). In addition, the 4-year cumulative incidence of non-relapse mortality (NRM) was 25% (95% CI 11–38%) and 22% (95% CI 5–39%), respectively (P>0.8), while the incidence of relapse was 22% (95% CI 5–39%) and 25% (95% CI 6–44%), respectively (P>0.8). In univariate analysis, the only variable that decreased OS and LFS by increasing NRM was the patient male/donor female sex combination (n=18 cases). The OS and NRM in these 18 cases were 37% and 40%, respectively, while the 56 cases with other sex combinations had much better outcomes (66% OS and 8% NRM, P=0.004 and P==0.001 for the comparison of OS and NRM, respectively). Trends were seen for improved OS and lower NRM in the CyTBI-CD34+ group in patients less than 40 years of age (P=0.1) and in patients receiving higher doses of CD34+ cells/kg in the FluBu-RIC group (P=0.1). Our single-center results suggest comparable outcomes for RIC alloPBSCT in high-risk adults with poor-risk AML and MDS in an early disease phase.

Efficacy of Reduced Intensity Conditioning (RIC) with FLU-BU-ATG and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Pediatric ALL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2314-2314 ◽  
Author(s):  
Reggie Duerst ◽  
David Jacobsohn ◽  
William T. Tse ◽  
Morris Kletzel
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Pediatric All ◽  
Very High ◽  
Reduced Intensity

Abstract Reduced Intensity Conditioning (RIC) regimens prior to allogeneic HSCT have gained acceptance in the treatment of adults with myelodysplasia, leukemia and multiple myeloma. RIC reduces the risk for regimen related morbidity and mortality enabling patients with pre-existing medical conditions that would have been precluded from allogeneic HSCT to attempt a curative approach. The resilience of pediatric patients (pts) following high-dose conditioning regimens and the concern that ALL cells are inherently more resistant to a graft-vs-leukemia effect have limited accrual of pediatric ALL pts to RIC protocols despite the potential benefit for reduced long-term morbidity. We report the experience of 10 pediatric ALL pts (6 M, 4 F, median age 9.5 years) treated for recurrent ALL with RIC and allogeneic HSCT. A uniform RIC regimen comprised of fludarabine, 30 mg/m2 for 6 consecutive days (days −10 through −5), followed by intravenous busulfan, 0.8 – 1 mg/kg for 8 doses or targeted AUC 4000 μMol*min for 2 doses (days −5 and −4) and equine ATG, 40 mg/kg or rabbit ATG, 2 mg/kg for 4 days (days −4 through −1) was administered. Pts with prior CNS involvement received whole brain (2400 cGy) and spinal (1800 cGy) irradiation immediately prior to the RIC. Stem cell sources included 7 unrelated donors and 3 matched sibs. 9 of 10 stem cell donations were peripheral blood stem cells (PBSC). The median cell doses infused were 6.5 x 108 MNC/kg and 4.2 x 106 CD34+ cells/kg. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A (CsA) alone in 5 patients, CsA and mycophenolate mofetil in 5 pts. Growth factor support was not used. Each of the pts had at least two very high-risk features--prior HSCT (n = 6), CR > 3/refractory disease (8), prior CNS disease (6), Ph+ (2), pre-exisiting neurologic (1) or cardiac (1) dysfunction or aspergillous infection (1). Full donor chimerism was achieved in 9 of 10 with a median time to reach an ANC >500/μl of 16 days (range 11–62) and an unsupported platelet count > 20,000/μl was achieved in 8 of 10 at a median of 25 days (15–67). 2 pts developed Gr IV acute GVHD, 2 of 5 pts surviving more than 100 days developed chronic GVHD. Only 3 patients have relapsed: 1 refractory T-ALL pt recurred day +27 and 2 Ph+ pts had a molecular relapse day +61 and +196. The latter pt is in subsequent continuous molecular remission for over 1 year on imatinib therapy. 6 pts have died, 5 in the first 100 days of HSCT from complications of GVHD (2), relapse (1), pulmonary failure (in 1 pt S/p 3 prior allogeneic HSCT) and PTLD (1). 1 pt succumbed from complications of chronic GVHD day +756. The RIC regimen and supportive care are primarily an outpatient experience. During the first 30 days post HSCT, pts spent an average of only 9 days in hospital (23 of the first 100 days). Despite very high-risk features, 4 of 10 pts survive (3 CCR) at a median of 500 days post HSCT. Thus, RIC and allogeneic HSCT also offers promise for efficacy in pediatric ALL.

Second Autologous or Allogeneic Transplantation after the Failure of First Autograft in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3329-3329
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima Saliba ◽  
Marcos de Lima ◽  
Daniel Couriel ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Albumin Level ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Common Causes

Abstract Background: Most patients undergoing high-dose therapy and autologous transplant for multiple myeloma eventually relapse. The optimal salvage treatment for these patients is not very well defined. Both autologous and allogeneic hematopoietic stem cell transplantations have been used for salvage. We analyzed the outcomes of second autologous or allogeneic transplants, performed as salvage in patients relapsing after an autograft. Methods: Fourteen patients received a second autograft for salvage, while thirty-four patients underwent allogeneic transplantation (related 24, unrelated 10). The median age at transplant was 52 years in the autologous group, and 51 years in the allogeneic group. The median interval between the first and the second transplant was 25 months in the autologous group and 17 months in the allogeneic group. The disease characteristics were similar in both autologous and allogeneic groups. Results: With a median follow-up of 10 months among survivors in each group, both autologous and allogeneic transplant groups had a response rate (complete + partial) of 64%. One hundred day nonrelapse mortality was 7% in the autologous group and 12% in the allogeneic group. Median disease-free survival (DFS) was 11 months in the autologous and 6 months in the allogeneic group. Median overall survival (OS) was 29 moths in the autologous and 14 months in the allogeneic group. 1-year DFS was 40% in the autologous group and 22% in the allogeneic group (p = 0.2). 1-year overall survival was 70% in the autologous and 53% in the allogeneic group (p = 0.3). The most common causes of non-relapse mortality were graft vs. host disease (62%) in the allogeneic group, and infections (100%) in the autologous group. On univariate analysis for DFS in allogeneic group, an interval of >1 year between the first and the salvage transplant was the only factor associated with a significantly better outcome (p = 0.01). Disease status at transplant, type of donor, tumor mass, β2 microglobulin level, and serum albumin level did not show any impact on the outcome. Conclusions: Both autografting and allografting are feasible as salvage for myeloma patients relapsing after the first autograft. A slightly better outcome with salvage autografting may be due to decreased toxicity.

Absence of High-Dose Consolidation Courses and Low Numbers of Allogeneic HSCTs Did Not Affect Overall Optimistic Results in B-Cell Precursor Ph-Negative Adult ALL Patients Treated By Non-Intensive but Non-Interruptive ALL-2009 Protocol: Data of the Russian ALL Study Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2497-2497
Author(s):  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Andrey Sokolov ◽  
Galina Kliasova ◽  
Larisa A. Kuzmina ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Normal Karyotype ◽  
Risk Groups ◽  
High Dose ◽  
Late Response ◽  
Allogeneic Hsct ◽  
Blast Cells

Abstract Introduction It is postulated that the improvement in the overall treatment outcome in adult Ph-negative ALL came from the implementation of more aggressive pediatric-like protocols and higher portion of allogeneic HSCT. Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the opposite approaches: less intensive but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933. Patients and Methods The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks prd/dexa with 3 instead of 4 dauno/vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks-continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications- with 1 day HD MTX and with 1 d HD ARA-C, both with L-asp and 3 ds dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11),L>100). No central MRD monitoring was performed. Since Apr 2009 till June 2015 20 centers had recruited 168 BCP-Ph-negative ALL pts with a median age 28 years (15-54), 84f/84 m. Full cytogenetics was available in 67,3% (n=113), 43,4% of them (n=49) had normal karyotype (NK), 10% (n=9%) had no mitosis, 47,6% (n=54) - different abnormalities (hypoploid-1, hyperploid-12, t(11q23)/MLL-8, del11q23-2, t(1;19)-2, t(12;21)-1;others-28). 26,7% of pts (n=45) were in the standard risk (SR) group (WBC <30, EGIL BII-III, LDH < 2N; no late CR; t(4;11)-negative), 56,5% (n=95) - in the high risk (HR) group (WBC >30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive), 28 patients (n=16,8%) were not qualified by the risk. The analysis was performed in June 2015. 158 pts were available for analysis. Results CR rate in 158 available for analysis pts was 87,7% (n=139), induction death occurred in 9,1% (n=14), resistance was registered in 3,2% (n=5). The majority of CR pts (87,8%) achieved it after prephase (12,2%, n=17) and the 1st phase of induction (75,6%, n=105). Late responders constituted 12,2% (n=17). Allogeneic BMT was performed only in 9 of 144 patients who survived induction (6,2%). Totally 31 pts (22,3%) had relapsed. At 60 mo OS for the whole group constituted - 50%, DFS - 51.3%. In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d, PRD resistance) age (>30 y) became statistically significant for OS, DFS and relapse probability (RP) (pic.1), abnormal karyotype - for DFS (30% vs 68%, p=0,04) and RP (42% vs 19%, p= 0,04). In a multivariate analysis no common risk factors were significant. Conclusions Our data demonstrate that the proposed treatment approach is rather effective. We believe that constant non-interruptive treatment without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that it should be very strict compliance of the pts to the protocol. All pts, mostly from the region hospitals who refused prolonged and constant treatment (~5%), relapsed. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Outcomes of Patients Treated with Matched and Mismatched Unrelated Donors Using High-Resolution HLA Typing at 12 Loci

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3537-3537
Author(s):  
Stefan O. Ciurea ◽  
Rima M. Saliba ◽  
Gabriela Rondon ◽  
Poliana A. Patah ◽  
Morgani Rodrigues ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Resolution ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Disease Status ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Progression Rate ◽  
Hematopoietic Stem ◽  
Poor Risk

Abstract Abstract 3537 Donor-recipient HLA mismatches are associated with increased morbidity and mortality after UD hematopoietic stem cell transplants (HSCT). We hypothesized that HLA-DP mismatches would worsen outcomes of HSCT using donors mismatched at HLA-A,-B,-C,-DRB1 or -DQB1 and evaluated 391 consecutive patients (pts) with myeloid malignancies treated at our institution with 0,1,2,3 mismatches out of 12 alleles typed by high resolution at HLA-A,-B,-C,-DR,-DQ,-DP loci. Eighty-one pts were 12/12, 180 pts were 11/12, 113 pts were 10/12, and 15 pts were 9/12 HLA match with the recipients. Characteristics of the 4 groups (12/12, 11/12, 10/12, 9/12) were similar except source of stem cells; 87% of pts with 9/12 donors received bone marrow versus 60–62% for the other 3 groups. Results: Two-year overall survival (OS) and progression-free survival (PFS) were 40%, 44%, 45%, 53% and 33%, 40%, 44%, 49%, respectively (p=NS). However, OS was significantly worse with increasing number of mismatches for patients with AML/MDS with poor-risk cytogenetics (p=0.005, HR 1.6, 95% CI 2.1–4.2). Except for the 9/12 group, pts had a significantly higher non-relapse mortality (NRM) (11%, 24%, 36%) and lower risk of progression (32%, 25%, 20%). In the 9/12 group, NRM was 27% and progression rate was 40%. Grade II-IV, III-IV aGVHD as well as cGVHD were also progressively worse with increasing number of mismatches. Gr II-IV and III-IV aGVHD rates were 35%, 37%, 41%, 69%, and 8%, 8%, 15%, 16%, respectively. Cumulative incidence of cGVHD was 35%, 39%, 44% and 61%, respectively. Compared with 11–12/12 donors, pts who received a 9–10/12 donor had significantly higher rates of gr III-IV aGVHD and cGVHD (p=0.03, HR 2.1, CI 1.1–3.7 and p=0.02, HR 1.5, CI 1.1–2.1, respectively). Univariate analysis revealed that there is less NRM with a 12/12 donor (vs. other) (p=0.008, HR 1.9, 95% CI 1.2–2.9), while in multivariate analysis, compared with a 12/12 donor, the use of a donor with mismatch was significantly associated with higher NRM [HR and 95%CI were 2.1 and 1.04–4.4 for 11/12 donor (p=0.04); 3.1 and 1.5–3.3 for 10/12 donor (p=0.003); 2.8 and 0.9–9.3 for a 9/12 donor (p=0.08), respectively] (Figure). In multivariate analysis, factors significantly associated with OS were disease status at transplant (active disease vs. not) (p<0.001), cytogenetics for AML/MDS pts (poor-risk vs. other) (p=0.006, HR) and the use of fludarabine and busulfan conditioning (Bu 130mg/m2 × 4 days and Flu vs. other) (p=0.04, HR 0.7, CI 0.5–0.98), while factors significantly associated with NRM were, in addition to degree of mismatch, disease status at transplant (p=0.008, HR 1.9, CI 1.2–3.1) and use of BuFlu conditioning (p=0.004, HR 0.5, CI 0.4–0.8). In conclusion, these results suggest that, using 12/12 high-resolution HLA typing, a progressively higher NRM is encountered for unrelated donor pts with higher number of mismatches, at least in part related to higher rates of GVHD. Matching at DP loci appears to be protective of NRM and is associated with improved survival for patients with AML/MDS with poor-risk cytogenetics. Disclosures: No relevant conflicts of interest to declare.

Reduced Intensity Allogeneic Stem Cell Transplantation for Hodgkin’s Disease. Outcome Depends Primarily on Disease Status at the Time of Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2322-2322 ◽  
Author(s):  
Stephen P. Robinson ◽  
Norbert Schmitz ◽  
Goli Taghipour ◽  
Anna Sureda
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Univariate Analysis ◽  
Disease Status ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Prior Therapy ◽  
Reduced Intensity

Abstract The use of reduced intensity conditioning regimens has extended the application of allogeneic stem cell transplantation to patients previously considered to old or medically unfit for high dose chemo-radiotherapy. However, the role of reduced intensity allogeneic transplantation (RIT) in the treatment of Hodgkin’s disease remains controversial due in part to the limited information available on the outcome of this procedure.We have therefore analysed a large cohort of patients with HD who have undergone RIT. A total of 311 patients from 127 centres were reported to the EBMT registry. Their median age at transplantation was 31.3 years (range 8–61) and 57% were male. They had undergone a median of 2 lines of prior therapy (range 1–6) and 45% of patients had undergone a prior high dose procedure. The median time from diagnosis to RIT was 3.2 years (range 0.25–24.5 years). At transplantation 158 patients had chemosensitive disease, 100 had chemoresistant disease and 53 had untested relapse. All patients underwent conditioning with reduced intensity regimens followed by bone marrow stem cell transplantation from matched family donors (221), matched unrelated donors (61) or mismatched donors (17). Peripheral blood stem cells were used in 263 patients, bone marrow in 46 and a combination in 2. In 294 cases assessable for engraftment sustained engraftment was seen in 93.6%. Chimerism studies performed in 115 patients revealed full donor chimerism in 85 and mixed chimerism in 30. Acute graft versus host disease (grade II–IV) was reported in 24% of patients and chronic graft versus host disease in 20%. With a median follow up of 1 year 59% of patients remain alive and the projected 2 year overall survival (OS) was 46%. In a univariate analysis only disease status at transplantation predicted for a worse OS (p<0.0001). The 100 day transplant related mortality (TRM) was 17% but this increased to 24% at 1 year and 27% at two years and was significantly worse for patients with chemoresistant disease at transplantation (p=0.02). Patient age and prior high dose therapy had no significant impact on TRM. At 1 and 2 years following transplantion 48% and 64% of patients had experienced relapse or progression of their disease. Only disease status at transplantation predicted for a higher risk of disease progression. Consequently the progression free survival (PFS) at 2 years was 26% and was significantly worse for patients with chemoresistant disease (p<0.0001). In univariate analysis patient age, prior high dose therapy and number of lines of prior therapy had no significant effect on PFS. Patients with HD may undergo RIT with acceptable toxicity irrespective of age and prior high dose therapy. However, the outcome depends upon the chemosensitivity of the disease at the time of transplantation and this factor should be a major consideration in the selection of patients for RIT.

Randomized trial of high-dose chemotherapy and autologous hematopoietic stem cell support for high-risk primary breast carcinoma

Cancer ◽  
2006 ◽  
Vol 106 (11) ◽  
pp. 2327-2336 ◽  
Author(s):  
Emer O. Hanrahan ◽  
Kristine Broglio ◽  
Deborah Frye ◽  
Aman U. Buzdar ◽  
Richard L. Theriault ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Breast Carcinoma ◽  
Randomized Trial ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Primary Breast Carcinoma ◽  
Hematopoietic Stem ◽  
Stem Cell Support ◽  
Cell Support

scholarly journals CAR T cells vs allogeneic HSCT for poor-risk ALL

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 501-507
Author(s):  
Caroline Diorio ◽  
Shannon L. Maude
Keyword(s):  
T Cells ◽  
High Risk ◽  
Survival Benefit ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Poor Risk ◽  
Car T ◽  
First Remission ◽  
Very High

Abstract For subgroups of children with B-cell acute lymphoblastic leukemia (B-ALL) at very high risk of relapse, intensive multiagent chemotherapy has failed. Traditionally, the field has turned to allogeneic hematopoietic stem cell transplantation (HSCT) for patients with poor outcomes. While HSCT confers a survival benefit for several B-ALL populations, often HSCT becomes standard-of-care in subsets of de novo ALL with poor risk features despite limited or no data showing a survival benefit in these populations, yet the additive morbidity and mortality can be substantial. With the advent of targeted immunotherapies and the transformative impact of CD19-directed chimeric antigen receptor (CAR)–modified T cells on relapsed or refractory B-ALL, this approach is currently under investigation in frontline therapy for a subset of patients with poor-risk B-ALL: high-risk B-ALL with persistent minimal residual disease at the end of consolidation, which has been designated very high risk. Comparisons of these 2 approaches are fraught with issues, including single-arm trials, differing eligibility criteria, comparisons to historical control populations, and vastly different toxicity profiles. Nevertheless, much can be learned from available data and ongoing trials. We will review data for HSCT for pediatric B-ALL in first remission and the efficacy of CD19 CAR T-cell therapy in relapsed or refractory B-ALL, and we will discuss an ongoing international phase 2 clinical trial of CD19 CAR T cells for very-high-risk B-ALL in first remission.

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