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. 2022 Nov;57(11):1671-1680.
doi: 10.1038/s41409-022-01780-w. Epub 2022 Aug 19.

Outcomes of two-step haploidentical allogeneic stem cell transplantation in elderly patients with hematologic malignancies

Xia Bi  1 , Usama Gergis  2 , John L Wagner  1 , Matthew Carabasi  1 , Joanne Filicko-O'Hara  1 , William O'Hara  1 , Thomas Klumpp  1 , Pierluigi Porcu  1 , Neal Flomenberg  1 , Dolores Grosso  1
Affiliations

Outcomes of two-step haploidentical allogeneic stem cell transplantation in elderly patients with hematologic malignancies

Xia Bi et al. Bone Marrow Transplant. 2022 Nov.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the best curative option for the majority of patients with hematologic malignancies (HM); however, many elderly patients are excluded from transplant and outcome data in this population is still limited. The novel two-step graft engineering approach has been the main platform for allo-SCT at Thomas Jefferson University since 2006. Following administration of the preparative regimen, we infuse donor lymphocytes, followed by cyclophosphamide to induce bidirectional tolerance, then infusion of CD34-selected cells. A total of 76 patients ≥ 65 years old with HM underwent haploidentical (haplo) allo-SCT on the two-step transplant platform between 2007 and 2021. The median time to neutrophil engraftment was 11 days and platelet engraftment was 18 days. With a median follow up of 44 months, the 3-year overall survival (OS) and progression-free survival (PFS) were 36.3% and 35.6%, respectively. The cumulative incidences of non-relapse mortality (NRM) and relapse at 3 years were 43.5% and 21.0% at 3 years, respectively. The cumulative incidence of grade III-IV acute graft-versus-host-disease (GVHD) was 11.1% at 6 months, and chronic GVHD requiring treatment was 15.1% at 2 years. The two-step haplo allo-SCT is a novel alternative platform for high-risk older HM patients, achieving fast engraftment, low relapse rates and promising survival.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1. Schema for the 2-step approach allogeneic stem cell transplantation.
In the myeloablative group (MA), recipients received total body irradiation (TBI) from day -10 to day -8 with total dose of 12 Gy. For the reduced intensity (RIC) group: RIC1 received fludarabine (Flu) 30 mg/m2 for 4 doses, busulfan (Bu) 3.2 mg/kg for 2 doses or thiotepa 5 mg/kg for 3 doses, and 2 Gy TBI; RIC2 received Flu 30 mg/m2 for 3 doses and 4 Gy TBI. Then donor lymphocyte infusion (DLI) which contains 2 × 108 CD3 + cells/kg was performed on day -6 after TBI. On day -3 and -2, recipients received cyclophosphamide (CY) 60 mg/kg/day. Tacrolimus (Tacro) and mycophenolate mofetil (MMF) were started on day -1. On day 0, CD34 + stem cells were infused, and growth factor (GF) was started on day + 1.
Fig. 2
Fig. 2. Cumulative incidence of acute GVHD Grade II–IV (left) and chronic GVHD Grade I–IV (right) with 95% confidence interval.
X-axis denotes time after transplantation in days.
Fig. 3
Fig. 3. Cumulative incidence of non-relapse mortality and relapse.
NRM Non-relapse mortality. X-axis denotes time after transplantation in years.
Fig. 4
Fig. 4. Kaplan-Meier overall survival (left) and progression-free survival (right) probability with 95% confidence interval.
X-axis denotes time after transplantation in years.
Fig. 5
Fig. 5. Survival outcomes with respect to various characteristics.
Overall survival for 76 patients by age (a), gender (b), diagnosis (c), remission status at transplant (d), performance status (e), hematopoietic cell transplantation comorbidity index (f), disease risk index score (G), intensity of conditioning regimen (h), Cytomegalovirus status (i), and donor age (j). X-axis denotes time after transplantation in years. P-values from log-rank test.
Fig. 5
Fig. 5. Survival outcomes with respect to various characteristics.
Overall survival for 76 patients by age (a), gender (b), diagnosis (c), remission status at transplant (d), performance status (e), hematopoietic cell transplantation comorbidity index (f), disease risk index score (G), intensity of conditioning regimen (h), Cytomegalovirus status (i), and donor age (j). X-axis denotes time after transplantation in years. P-values from log-rank test.
Fig. 6
Fig. 6. Forrest plot of multivariate analysis for all patients by selected characteristics.
AML Acute myeloid leukemia, ALL Acute lymphocytic leukemia, MDS Myelodysplastic syndrome, MPN Myeloproliferative disorder, NHL Non-Hodgkin lymphoma, CLL Chronic lymphocytic leukemia, CR Complete remission, PS Performance status, KPS Karnofsky, HCT-CI Hematopoietic cell transplantation comorbidity index, RDRI Disease risk index score, MAC Myeloablative, RIC2 Flu and 4 Gy TBI, RIC1 Flu/Bu and 2 Gy TBI, CMV Cytomegalovirus, CI confidence interval. **statistically significant.
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