scholarly journals Long-term outcomes in patients with high-risk myeloid malignancies following matched related donor hematopoietic cell transplantation with myeloablative conditioning of BU, etoposide and CY

2010 ◽  
Vol 46 (2) ◽  
pp. 192-199 ◽  
Author(s):  
S Naik ◽  
R Wong ◽  
S Arai ◽  
J Brown ◽  
G Laport ◽  
...  
2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7033-7033
Author(s):  
S. G. Naik ◽  
R. Negrin ◽  
G. Laport ◽  
D. Miklos ◽  
J. Shizuru ◽  
...  

7033 Patients (pts) with high risk (HR) or advanced myeloid malignancies have limited effective treatment options. These include high-dose therapy followed by allogeneic hematopoietic cell transplantation (HCT). We report a single institution long-term follow-up of 96 pts, median age 50 (20–60) yrs, who received HLA matched related HCT between 1992 and 2007. All pts were treated with a uniform preparatory regimen: busulfan 16.0 mg/kg (d-8 to-5), etoposide 60mg/kg (d-4), cyclophosphamide 60mg/kg (d-2), and graft-versus-host-disease (GVHD) prophylaxis of cyclosporine and prednisone. Disease status at transplantation was induction failure (IF) acute myeloid leukemia (AML) (n = 10), HR AML in 1st complete remission (CR1) n = 11, in CR2 (n = 5), in CR3 (n = 2), relapsed refractory (RR) AML (n = 14), chronic myeloid leukemia (CML) in second chronic phase (n = 6), blast crisis (n = 2), myelofibrosis (n = 6), myeloproliferative disorders (n = 2), and MDS (n = 38). Thirty-six % (n = 35) of pts received bone marrow while 64 % (n = 61) received G-CSF mobilized peripheral blood mononuclear cells (PBMC). With a median follow up of 5.6 yrs (1.6–14.6 yrs) actuarial 5-year overall survival (OS) was 32% (95% CI 22–42%) and 5-year probability for freedom from progression (FFP) was 64% (95% CI 52%-76%). Relapse rate was 32% at 1 year and remained at 36% (95%CI 24%-48%) at 2 and 5 years with no further increase in relapse beyond two years. Non-relapse mortality (NRM) was 29 % (95% CI 20%5–38%) at day 100 and 39% (95% CI 29%-49%) at one yr. Cumulative incidence of acute (grade 3–4) and chronic GVHD was 28% (95% CI 19%-37%) and 38% (95% CI 24%-52%), respectively. There was no statistically significant difference in OS; 31% versus 32% (p = 0.89) or FFP 71% versus 60% (p = 0.29) for recipients of BM versus PBMC with similar results in IF and RR AML. These results confirm that pts with high-risk or advanced myeloid malignancies can achieve long-term survival following myeloablative allogeneic HCT with aggressive conditioning. Relapse and acute GVHD remain significant causes of mortality. Strategies to augment graft-versus-tumor reactions and reduce GVHD remain essential for improving long-term outcomes. No significant financial relationships to disclose.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5534-5534
Author(s):  
Moaath Mustafa Ali ◽  
Donna M Abounader ◽  
Lisa A. Rybicki ◽  
Jamie Starn ◽  
Christina Ferraro ◽  
...  

Abstract Allogeneic hematopoietic cell transplantation (alloHCT) is a curative therapy for high-risk acute lymphoblastic leukemia (ALL). However, long-term outcomes after alloHCT for adult ALL have not been well described. We conducted a retrospective cohort study of 72 consecutive adult ALL patients who underwent a first myeloablative alloHCT at our institution from January 2000-December 2013. Median age at HCT was 38 yrs (range, 18-62), 40 (56%) were male, 18 (38%) had high HCT CI score, 14 (19%) had prior CNS leukemia and 35 (49%) had BCR-ABL+ disease. Donor source was HLA-matched related donor for 50% patients and 90% received PBSC as graft source. All patients were transplanted in CR (72% were in 1st or 2nd CR) and 92% received T-cell replete grafts. Median time from diagnosis to alloHCT was 5 months (range, 2-90). The incidences of grade II-IV and III-IV acute GvHD, chronic GvHD and extensive chronic GvHD were 43%, 13%, 51% and 36%, respectively. The median follow-up for our cohort is 76 months. At 6 years after HCT, probability of overall survival (OS) was 33% (95% CI, 21-44%) and relapse-free survival (RFS) was 30% (95% CI, 19-42%), and the cumulative incidence of relapse was 36% (95% CI, 25-48%) and non-relapse mortality (NRM) was 37% (95% CI, 26-49%). The most common causes of death were relapse (43%) and infection (21%); majority of relapses occurred within the first 2-years post-transplantation. There were no second cancer related deaths. In multivariable analyses, factors significantly associated with OS were HCT CI score (HR 2.69 for high vs. low/int., P=0.002) and CMV status (HR 2.62 for donor+ vs. others, P=0.05). HCT CI score was the only predictive factor for RFS (HR 2.26 for high, P=0.007). We also compared outcomes by BCR-ABL status. BCR-ABL+ patients were older (median age 42 vs. 36 yrs, p=0.02), had low HCT CI score (34% vs 22%, p=0.01), were more likely to be in CR1 (74% vs. 32%, p=0.002), and as a result, proceeded to HCT sooner after diagnosis (median 4 vs 7 months, p=<0.001). For BCR-ABL+ and BCR-ABL- patients, 6 year OS was 41% and 25%, RFS was 40% and 21%, relapse was 27% and 45% and NRM was 38% and 36% (P=NS for all comparisons). Myeloablative alloHCT can provide long-term survival for selected high-risk adult ALL patients. Relapses are relatively uncommon after 2 years post-transplant. Long-term NRM is high in this population and we did not observe a plateau in its incidence until 7.5 years post-transplant, suggesting the need for long-term follow up to prevent and manage late complications of alloHCT. Figure 1. Figure 1. Disclosures Majhail: Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.


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