Enhanced Recovery Program in Older Patients Undergoing Allogeneic Stem Cell Transplantation (ER-SCT): First Year Outcomes

Abstract Abstract 202 Introduction: In a completed study (NCT00337519), patients with advanced B-CLL received allogeneic stem cell transplantation (SCT) after cytoreductive treatment with alemtuzumab followed by a wash-out period for the antibody and conditioning with fludarabine/busulfan. Aim of the present investigation was to correlate flow cytometric levels of minimal residual disease (MRD) in the peripheral blood at different time points after transplantation with patient outcome. Patients and Methods: In 58 CLL patients 900 flow cytometric MRD investigations (at least 4 measurements/patient: at day 30, between days 31–100, 101–180, and 181–365 after SCT) were performed measuring the following CLL phenotype: CD19posCD5posCD20dimCD79bneg. Therefore, a 4-color-approach (FACSCalibur, until 2006) or an 8-color-approach then in combination with T- and NK cell antigens (FACSCanto) was performed. A patient was defined as MRD negative if less than 0.05% CLL cells were detectable or as relapse if more than 0.05% CLL cells were again redetectable in at least two successive investigations. For assessment of progression-free survival (PFS), clinical progress was defined according to the NCI criteria. Results: The median follow up time after SCT was 536 days (range: 44d –1758d). Considering all 58 transplanted patients the probability of one-year overall survival (OS) including the 95% confidence interval was 83% ± 10% (2-year OS: 76%±12%) and of one-year PFS 74% ± 12% (2-year PFS: 50%±16%). In the majority of cases flow cytometric MRD negativity was achieved within the first year post SCT with a cumulative incidence of 36%±13% at day 100 and of 73%±12% at one year, respectively. Only two additional patients became MRD negative within the second year post SCT. Patients who achieved MRD negativity until day 365 showed a significantly better 2-year OS compared to the MRD positive group (96%±7% vs. 56%±49%; p=0.009). Remarkably, the 2-year PFS of patients achieving flow cytometric MRD negativity until day 365 was also significantly better than in the MRD positive cases (83%±16% vs. 0%, 3-year: 75%±20% vs. 0%; p=0.002). Of note, early flow cytometric MRD negativity until day 100 was not informative concerning OS or PFS at one year (88%±13% vs. 79%±15% and 77%±18% vs. 72%±18%). The flow cytometric MRD status was one trigger to speed the taper of cyclosporine or to give DLI. Interestingly, this kind of immunomodulation resulted in flow cytometric MRD negativity in eight out of nine patients after a median of 130 days. The probability of relapse in the investigated patient cohort was 15%±10% after 1 year and 31%±14% after 2 years. Thus, 8/14 patients showed a clinical relapse in parallel with flow cytometric MRD positivity. Two patients featured an isolated flow relapse with MRD at two successive investigations. Four patients showed a mere nodal relapse, all but one occurring within the first year post SCT. Conclusion: In summary, the present flow cytometric MRD study in B-CLL patients elucidates the dynamics of remission induction and relapse in the first year post SCT. In the majority of patients MRD is eradicated between day +100 and day +365 which is the time interval when chronic GvHD occurs in most cases. Therefore, close monitoring of MRD status in the first year after SCT is necessary. Once patients are flow cytometrically MRD negative at day 365, they seem to have a high probability of long term survival. Disclosures: Schetelig: Schering-Bayer: Research Funding.

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Myeloablative Conditioning Using Intravenous Busulfan for Older Patients (55 Years and Older) in Allogeneic Stem Cell Transplantation -Final Analysis of FB09 and Fb10 Study of JSCT-

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2017.12.417 ◽

2018 ◽

Vol 24 (3) ◽

pp. S405-S406

Author(s):

Naoyuki Uchida ◽

Kana Matsumoto ◽

Toru Sakura ◽

Michihiro Hidaka ◽

Toshihiro Miyamoto ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Older Patients ◽

Final Analysis ◽

Myeloablative Conditioning

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Older Patients With High-Risk MDS Benefit From Allogeneic Stem Cell Transplantation

The Hematologist ◽

10.1182/hem.v18.6.202161 ◽

2021 ◽

Vol 18 (6) ◽

Author(s):

Michael J. Hochman ◽

Amy DeZern

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Older Patients

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High Cure Rate By Allogeneic Stem Cell Transplantation for Myelofibrosis Patients Aged 65 or Older

Blood ◽

10.1182/blood-2018-99-113255 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4637-4637 ◽

Cited By ~ 1

Author(s):

Giulia Daghia ◽

Tatjana Zabelina ◽

Gaby Zeck ◽

Ute-Marie von Pein ◽

Maximilian Christopeit ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Older Patients ◽

Univariate Analysis ◽

The Other ◽

Reduced Intensity Conditioning ◽

Male Donor ◽

Reduced Intensity

Abstract Introduction Myelofibrosis (MF) is predominantly a disease of the elderly with a median age of 65 years at diagnosis. Allogeneic stem cell transplantation (ASCT), which is associated with substantial treatment-related morbidity and mortality, is the only potentially curative option so far. The development of reduced intensity conditioning (RIC) regimens has enabled transplant to be performed successfully in older patients. To evaluate the outcome of transplantation among elderly patients, we conducted a retrospective analysis of results in 46 patients, aged 65 years or older, who were transplanted between 2002 and 2018 at the University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany. Patients and methods Retrospective data from 46 patients with primary or secondary MF, who underwent ASCT, were collected. Median age at ASCT was 67 years (r: 65-74). 76% of patients were classified as MF-3 according to the WHO criteria. DIPSS risk status was intermediate-1 in 4% of patients, intermediate-2 in 61% and high in 33%. 70% of patients had mutation in JAK2, 17% in CALR and 9% in MPL. All patients received peripheral blood stem cell (PBSC) as graft source. Stem cell donor was related in 9% of patients, unrelated in 91%; 74% of patients had a completely HLA-matched donor, whereas 26% had at least 1 allele or antigen mismatch. 85% of patients received busulfan 10 mg/kg orally (or 8 mg/kg intravenously) plus fludarabine (150 mg/m2) reduced intensity conditioning regimen, whereas 15% received myeloablative conditioning with busulfan 16 mg/kg orally (or 12.8 mg/kg intravenously) plus fludarabine (150 mg/m2). 96% of the patients received anti-T-lymphocyte globulin (Grafalon®, Neovii, Germany) at a cumulative dose of 30 mg/kg for matched related donor (MRD) transplants and 60 mg/kg for matched/mismatched unrelated donor (MUD/MMUD) transplants. Further GVHD prophylaxis consisted of cyclosporine A and mycophenolate from day +1 to +28. Results Engraftment rate was 94%, with a median time to neutrophil engraftment of 13 days (r: 10-19). Two patients (4%) experienced primary graft failure (PGF), one received a second ASCT with successful engraftment, while the other had further PGF after second ASCT and died of infection after third ASCT. Platelet engraftment rate was 87% and was reached in a median time of 21 days (r: 10-293). Five patients (11%) developed secondary poor graft function and four received CD34+ selected PBSC boost, two achieving complete remission (CR) and one obtaining CR with incomplete platelet recovery (CRp). 52% of patients experienced acute GVHD grade I to IV, while the overall rate of chronic GVHD was 56%, which was moderate disease in 24% and severe disease in 13%. After a median follow-up of 4 years, 6-year estimated progression-free survival (PFS) and overall survival (OS) were 60% (95% CI: 42-78) and 64% (95% CI: 48-80), respectively. In the univariate analysis, male donor sex was the only significant factor for improved OS and PFS at 6 years (P=.001 and P=.003, respectively). A positive impact on OS was observed for mutation in CALR (P=.05), as previously reported. Interestingly, survival was not significantly different in patients aged 65-70 years compared with those aged 71-74 years. Cumulative incidence of non-relapse mortality (NRM) was 29% at 4 years (95% CI: 13-45). Major causes of death were infections (n=4) and GVHD (n=3). The only significant factor for lower NRM in the univariate analysis was male donor sex vs female (NRM 17% vs 58%, P=.004). No NRM occurred in CALR-mutated patients (p=0.00). Cumulative incidence of relapse at 6 years was 10% (95% CI: 0-22): one patient durably restored molecular response after early tapering of cyclosporine, one died because of GVHD without any further treatment, one achieved a long-lasting CR after donor lymphocytes infusions (DLI), while two patients underwent a second ASCT after DLI alone in one case and DLI plus azacitidine in the other, with long-term CR in the former. Conclusion Our results show that RIC regimen followed by allogeneic stem cell transplantation in older patients with myelofibrosis is a curative treatment option. These results are encouraging for older MF patients with minimal comorbidities. In addition to Hematopoietic cell transplantation-specific comorbidity index (HCT-CI), a comprehensive geriatric assessment could be a useful tool for a better selection of patients with the aim to further reduce NRM. Disclosures No relevant conflicts of interest to declare.

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