scholarly journals Allogeneic Hematopoietic Cell Transplantation with Myeloablative Conditioning Regimen of Reduced Toxicity Is Associated with Favorable Survival in Patients with Secondary Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Eleni Gavriilaki ◽  
Chrysavgi Lalayanni ◽  
Ioanna Sakellari ◽  
Christos Varelas ◽  
Despina Mallouri ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Transplant Recipients ◽  
Myeloablative Conditioning ◽  
Comorbidity Index ◽  
Reduced Toxicity ◽  
Reduced Intensity

Background: Secondary or treatment-related acute myeloid leukemia (sAML) is associated with poor outcomes. Although allogeneic hematopoietic cell transplantation (alloHCT) is the treatment of choice, patient eligibility criteria and optimal conditioning regimen remain under study. We have previously shown an advantage of a myeloablative conditioning regimen with reduced toxicity (Fludarabine 150mg/m2, Treosulfan 42g/m2, FluTreo) compared to a reduced intensity regimen. However, the long-term effects of this regimen remain unknown, especially in comparison to patients not receiving alloHCT. Aims: We hypothesized that patients transplanted with FluTreo would have a long-term survival advantage over other treatment alternatives. Methods: We retrospectively studied consecutive patients treated for sAML in our center over the last two decades (1998-2018). Exclusion criteria were: age>70 years, ECOG performance status≥3 at presentation, induction regimens≤2, and autologous or haploidentical HCT because these were performed in individual patients. Since 2013, we have introduced FluTreo for patients with a suitable donor that would have been previously eligible only for reduced intensity conditioning/RIC. The following factors were studied in the whole cohort: age, type of disease (treatment-related or post myelodysplastic syndrome/MDS), previous intensive chemotherapy cycles, cytogenetic risk, overall (OS) and disease-free survival (DFS). In transplant recipients, we also recorded HCT-comorbidity index/CI score, cumulative incidence (CI) of graft-versus-host disease (GVHD), and treatment-related mortality (TRM). Follow-up was calculated from diagnosis in the whole cohort; and from date of transplant in the sub-group analysis of transplant recipients. Results: We studied 19 FluTreo recipients compared to 46 recipients of other conditioning regimens (38 myeloablative and 8 RIC), and 52 patients treated only with chemotherapy. Complete remission (CR) had been achieved in all FluTreo recipients before HCT, compared to 53% of other transplants, and 44% of chemotherapy only patients (p<0.001). As expected, median age was increased in FluTreo and chemotherapy only patients (59 and 58 years respectively), compared to other transplants (48 years, p<0.001). There was no other difference in baseline characteristics. With a median follow-up of 43 (range 13-204) months in surviving patients, 4-year OS was 40.3% in FluTreo versus 31.3% in other transplants and 11.8% in chemotherapy only patients (p<0.001, Figure 1A). In the multivariate analysis, achieving CR (p<0.001) and the FluTreo group (p<0.001) were associated with favorable OS, independently of age and cytogenetic risk. 4-year DFS was 32.3% in FluTreo, versus 29.3% in other transplants and 10.2% in chemotherapy only patients (p=0.001, Figure 1B). Within transplanted patients, there was no significant difference in GVHD, relapse and TRM between FluTreo and other transplants. Within the FluTreo group, acceptable rates of CI in severe acute and extensive chronic GVHD were observed (15.2% and 18.4%, respectively). Similarly, 4-year CI of TRM reached 30.4%, despite a median HCT-CI of 3 (0-7), age of 59 (51-67) years, 4 lines of treatment (3-6), and a majority of matched unrelated donors (13/19). Conclusion: Our real-world study confirms that alloHCT with FluTreo expands the transplant population with similar safety and efficacy to previous transplant modalities in sAML patients. Achievement of CR remains a major predictor of OS in these patients. The choice of alloHCT in this unique patient population of a rather older age and comorbidity index needs to be revisited. Figure 1 Disclosures Gavriilaki: Omeros Pharmaceuticals: Consultancy.

Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3456-3462 ◽  
Author(s):  
Partow Kebriaei ◽  
Michelle A. Detry ◽  
Sergio Giralt ◽  
Antonio Carrasco-Yalan ◽  
Athanasios Anagnostopoulos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) remains an effective strategy for inducing durable remission in chronic myeloid leukemia (CML). Reduced-intensity conditioning (RIC) regimens extend HSCT to older patients and those with comorbidities who would otherwise not be suitable candidates for HSCT. The long-term efficacy of this approach is not established. We evaluated outcomes of 64 CML patients with advanced-phase disease (80% beyond first chronic phase), not eligible for myeloablative preparative regimens due to older age or comorbid conditions, who were treated with fludarabine-based RIC regimens. Donor type was matched related (n =30), 1 antigen-mismatched related (n =4), or matched unrelated (n =30). With median follow-up of 7 years, overall survival (OS) and progression-free survival (PFS) were 33% and 20%, respectively, at 5 years. Incidence of treatment-related mortality (TRM) was 33%, 39%, and 48% at 100 days, and 2 and 5 years after HSCT, respectively. In multivariate analysis, only disease stage at time of HSCT was significantly predictive for both OS and PFS. RIC HSCT provides adequate disease control in chronic-phase CML patients, but alternative treatment strategies need to be explored in patients with advanced disease. TRM rates are acceptable in this high-risk population but increase over time.

The Dose of CD34+ Cells Negatively Impacts the Outcome of Patients Treated with Genoidentical Allo SCT Prepared with a Reduced Intensity Conditioning (RIC).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1086-1086
Author(s):  
Didier Blaise ◽  
Laure Farnaut ◽  
Catherine Faucher ◽  
Sabine Furst ◽  
Jean El Cheikh ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Cox Model ◽  
Disease Status ◽  
Probability Estimates ◽  
Cd34 Cells ◽  
Comorbidity Index ◽  
And Function ◽  
Donor Source

Abstract While RIC are presently commonly used, most of the reports suffer from insufficiencies limiting knowledge acquisition: small populations, short follow-up, heterogeneities in the RIC intensity or the donor source. We report here 100 patients with hematological malignancies (HM) treated with geno-identical SCT after the same RIC in a single center from 2000 until 2006. All patients received oral busulfan (8mg/m2), thymoglobulin (2.5 mg/kg) and Fludarabine (150 to 180 mg/m²) (FBT conditioning). All grafts were PBSC from a match sibling donor. All grafts were monitored for CD34, CD3, CD4, CD8, CD19 and CD56+ cells (notably CD34= 5.6 (1.5–22) × 10e6/kg; CD3= 317 (112–887) × 10e6/kg). Median age was 50 (18–64). Hematopoietic cell transplantation comorbidity index (HCT-CI) was 0, 1–2 and > 2 in 31, 39 and 23 of the 93 evaluable patients. All patients received post-graft CSA. Diagnoses included acute leukemia (39%), Myeloid (16%) or Lymphoid (45%) malignancies. 53, 14 and 33 pts were in CR, progression or stable disease. Minimal and median follow-up are respectively 6 and 34 months. All but one engrafted reaching full lymphoid donor chimerism prior to day 100 in 85% of the cases. 55 pts presented aGVHD (G1: 12; G2: 22; G3: 12; G4: 9) for a cumulative incidence (CI) of G2–4 aGVHD of 43% (33–53); 91 patients were evaluable for cGVHD with a 79% (71–87) CI (Lim= 20%; Ext: 80%). In a multivariate analysis cGVHD occurrence could be predicted by 2 independent factors: lower dose of CD34 (but no impact of CD3, CD4, CD8, CD19 or CD56) (odd ratio (OR): 0.79 (0.69–0.90)) and grade 2–4 aGVHD (OR: 1.16 (1.01–1.32)). TRM CI was respectively 5%, 14% and 19% (11–27) at 3, 12 months and overall. TRM was strongly associated with aGVHD occurrence (TRM CI: grade 2–4 aGVHD: 37% (23–51); grade 0–1 aGVHD: 7% (0–14): p<.01). Relapse CI was 15% (8–22) at a median of 169 days (30–769). Disease control was significatively associated with cGVHD occurrence (Relapse CI: cGVHD: 10% (3–17); no cGVHD: 42% (14–70): p=.01). 5 year overall survival (OS) and LFS probability estimates are 62% (50–72) and 60% (48–72) with a plateau starting after 3.5 years. Outcome was similar for the patients above or under 50 and for the different diagnoses. HCT-CI did not show any influence on outcome. In a Cox model analysis, LFS was independently affected by only 2 pre-transplant variables: disease status (CR vs. no CR) (OR=0.45; p=.022) and the dose of infused CD34+ cells (> or < 5.6 × 10e6 CD34+ cells) (OR: 2.04; p=.039). In accordance with above, patients with higher CD34+ cells presented less cGVHD (cGVHD CI: CD34 < 5.6: 98% (94–100); CD34 > 5.6: 76% (64–88) ; p<0.01). These data confirm that FBT RIC, combining myeloablation (Busulfan) and limited Thymoglobulin, is efficient in a wide population in term of age and diagnosis conducting to sustained long term OS and EFS with limited TRM. They suggest also that after RIC, graft composition and function probably in relation with G-CSF mobilization might impact allogeneic effect and invite revisiting this subject in this context.

scholarly journals Primary immunosuppressive TNI-based conditioning regimens in pediatric patients treated with haploidentical hematopoietic cell transplantation

2021 ◽  
Author(s):  
D. Wegener ◽  
P. Lang ◽  
F. Paulsen ◽  
N. Weidner ◽  
D. Zips ◽  
...  
Keyword(s):  
Single Dose ◽  
Cell Transplantation ◽  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Growth Failure ◽  
Hematopoietic Cell ◽  
Haploidentical Hematopoietic Cell Transplantation

Abstract Purpose This retrospective analysis aims to address the toxicity and efficacy of a modified total nodal irradiation (TNI)-based conditioning regimen before haploidentical hematopoietic cell transplantation (HCT) in pediatric patients. Materials and methods Patient data including long-term follow-up were evaluated of 7 pediatric patients with malignant (n = 2) and non-malignant diseases (n = 5) who were treated by a primary TNI-based conditioning regimen. TNI was performed using anterior/posterior opposing fields. All patients received 7 Gy single-dose TNI combined with systemic agents followed by an infusion of peripheral blood stem cells (n = 7). All children had haploidentical family donors. Results Engraftment was reached in 6/7 children after a median time of 9.5 days; 1 child had primary graft failure but was successfully reconditioned shortly thereafter. After an average follow-up time of 103.5 months (range 8.8–138.5 months), event-free (EFS) and overall survival (OS) rates were 71.4% and 85.7%, respectively. One child with a non-malignant disease died 8.8 months after transplantation due to a relapse and a multiple organ failure. Follow-up data was available for 5/6 long-term survivors with a median follow-up (FU) of 106.2 months (range 54.5–138.5 months). Hypothyroidism and deficiency of sexual hormones was present in 3/5 patients each. Mean forced expiratory volume in 1 s (FEV1) after TNI was 71%; mean vital capacity (VC) was 78%. Growth failure (< 10th percentile) occurred in 2/5 patients (height) and 1/5 patient (weight). No secondary malignancies were reported. Conclusion In this group of patients, a primary single-dose 7 Gy TNI-based conditioning regimen before HCT in pediatric patients allowed sustained engraftment combined with a tolerable toxicity profile leading to long-term OS/EFS. Late toxicity after a median FU of over 9 years includes growth failure, manageable hormonal deficiencies, and acceptable decrease in lung function.

Long-term outcomes of high-dose therapy using busulfan, etoposide, and cyclophosphamide followed by allogeneic hematopoietic cell transplantation for patients with high-risk or advanced stages of myeloid malignancies

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7033-7033
Author(s):  
S. G. Naik ◽  
R. Negrin ◽  
G. Laport ◽  
D. Miklos ◽  
J. Shizuru ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Long Term Outcomes ◽  
High Dose Therapy ◽  
Myeloid Malignancies

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.

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