HLA-mismatched unrelated donor transplantation using TLI-ATG conditioning has a low risk of GVHD and potent antitumor activity

Spinner, Michael A.; Fernández-Viña, Marcelo; Creary, Lisa E.; Quinn, Olivia; Elder, Linda; Arai, Sally; Johnston, Laura; Meyer, Everett; Miklos, David B.; Muffly, Lori; Negrin, Robert S.; Shizuru, Judith A.; Weng, Wen‐Kai; Laport, Ginna G.; Strober, Samuel; Lowsky, Robert; Rezvani, Andrew R.

doi:10.1182/bloodadvances.2017007716

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…Of those patients, 341 have been reported in prior publications, but with limited follow-up. 10,11,[22][23][24]29 Diagnoses included acute myeloid leukemia (AML; n 5 193), MDS (n 5 94), myelofibrosis (n 5 9), chronic myeloid leukemia (CML; n 5 12), acute lymphoblastic leukemia (ALL; n 5 14), chronic lymphocytic leukemia (CLL; n 5 80), NHL (n 5 175), and HL (n 5 35). Fortyfour percent of patients had HLA-MRDs, 41% had HLA-matched unrelated donors (MUDs; matching at 10 of 10 alleles), and 15% had partially HLA-mismatched unrelated donors (MMUDs), matching at 8 to 9 of 10 alleles (including 3% mismatched at HLA-DQB1 only).…”

Section: Patient Characteristicsmentioning

confidence: 99%

Nonmyeloablative TLI-ATG conditioning for allogeneic transplantation: mature follow-up from a large single-center cohort

Spinner¹,

Kennedy²,

Tamaresis³

et al. 2019

Blood Advances

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Nonmyeloablative total lymphoid irradiation and antithymocyte globulin (TLI-ATG) conditioning is protective against graft-versus-host disease (GVHD), while retaining graft-versus-tumor activity across various hematologic malignancies. We report our comprehensive experience using TLI-ATG conditioning in 612 patients with hematologic malignancies who underwent allogeneic transplantation at Stanford University from 2001 to 2016. All patients received granulocyte colony-stimulating factor–mobilized peripheral blood grafts and cyclosporine and mycophenolate mofetil for GVHD prophylaxis. The median age was 60 years (range, 21-78), with a median follow-up of 6.0 years (range, 1.0-16.4). Common diagnoses included acute myeloid leukemia (AML; n = 193), myelodysplastic syndrome (MDS; n = 94), chronic lymphocytic leukemia (CLL; n = 80), non-Hodgkin lymphoma (NHL; n = 175), and Hodgkin lymphoma (HL; n = 35). Thirty-four percent of patients had a comorbidity index ≥3, 30% had a high to very high disease risk index, and 56% received unrelated donor grafts, including 15% with HLA-mismatched donors. Ninety-eight percent underwent transplant in the outpatient setting, and 57% were never hospitalized from days 0 through 100. The 1-year rates of nonrelapse mortality (NRM), grade II-IV acute GVHD, and extensive chronic GVHD were 9%, 14%, and 22%, respectively. The 4-year estimates for overall and progression-free survival were 42% and 32% for AML, 30% and 21% for MDS, 67% and 43% for CLL, 68% and 45% for NHL, and 78% and 49% for HL. Mixed chimerism correlated with the risk of relapse. TLI-ATG conditioning was well tolerated, with low rates of GVHD and NRM. Durable remissions were observed across hematologic malignancies, with particularly favorable outcomes for heavily pretreated lymphomas. Several efforts are underway to augment donor chimerism and reduce relapse rates while maintaining the favorable safety and tolerability profile of this regimen.

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Section: Patient Characteristicsmentioning

confidence: 99%

Nonmyeloablative TLI-ATG conditioning for allogeneic transplantation: mature follow-up from a large single-center cohort

Spinner¹,

Kennedy²,

Tamaresis³

et al. 2019

Blood Advances

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“…The low risk of NRM and GVHD was observed even among patients with a partially HLAmismatched unrelated donor, which is consistent with our prior experience using TLI-ATG conditioning. 9 Although it is certainly reasonable to first consider BV and the immune checkpoint inhibitors for HL patients who relapse after autologous HCT, our data lend strong support that appropriate patients should continue to be referred for transplant consultation because they may be effectively salvaged and achieve durable remissions with nonmyeloablative allogeneic HCT. It remains unclear whether the pretransplant use of immune checkpoint inhibitors may increase the risk for GVHD.…”

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confidence: 67%

Allogeneic transplantation using TLI-ATG conditioning for Hodgkin lymphoma after failure of autologous transplantation

Spinner¹,

Advani²,

Hoppe³

et al. 2018

Blood Advances

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“…The use of ATG as GVHD prophylaxis was associated with better overall survival as a result of reducing mortality due to GVHD in patients with indolent FL. [31][32][33][34] The association of low-dose ATG use with HCT outcomes in patients with tFL has not been specifically examined in previous studies. Our results showed that the adminis-…”

Section: Discussionmentioning

confidence: 99%

Outcomes of hematopoietic cell transplantation for transformed follicular lymphoma

Ida

Inamoto²,

Fukuhara

et al. 2021

Hematological Oncology

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This study characterized the outcomes of patients who underwent hematopoietic cell transplantation (HCT) for transformed follicular lymphoma (tFL), and clarified the association of low-dose anti-thymocyte globulin use with outcomes after allogeneic HCT. The retrospective study cohort included 74 consecutive patients who underwent autologous (n = 23) or allogeneic (n = 51) HCT at our center from 2000 to 2017. Compared with the allogeneic HCT group, the autologous HCT group underwent fewer systemic regimens before HCT (median 2 vs. 5, p < 0.001) and were more likely to have chemosensitive disease at HCT (100% vs. 82%, p = 0.05), while age, sex and HCT-specific comorbidity index were similar between the two groups. With a median follow-up of 5.8 years among survivors, the 5-year probability of progression-free survival was 64% after autologous HCT and 55% after allogeneic HCT (p = 0.21). The 5-year cumulative incidence of non-relapse mortality was 0% after autologous HCT and 9.5% after allogeneic HCT (p = 0.062). The 5-year cumulative incidence of disease progression was similar between autologous and allogeneic HCT (36% vs. 36%, respectively, p = 0.88). In the allogeneic HCT group, the use of low-dose anti-thymocyte globulin was associated with a lower incidence of severe acute GVHD but not with an increased risk of mortality or disease progression. More than half of patients with early phase chemosensitive tFL and approximately half of those with advanced-phase tFL achieved long-term progression-free survival with autologous and allogeneic HCT, respectively. Disease progression was the major cause of treatment failure after both types of HCT. Further strategies are needed to reduce the risk of disease progression.

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HLA-mismatched unrelated donor transplantation using TLI-ATG conditioning has a low risk of GVHD and potent antitumor activity

Abstract: Key Points Nine of 10 MMUD HCTs have at least equivalent outcomes as 10 of 10 MUD HCTs using TLI-ATG with low rates of GVHD and nonrelapse mortality. MMUD HCT using TLI-ATG is well suited for patients with lymphoid malignancies given the low relapse rates without increased GVHD.

Cited by 9 publications

References 39 publications

Nonmyeloablative TLI-ATG conditioning for allogeneic transplantation: mature follow-up from a large single-center cohort

Nonmyeloablative TLI-ATG conditioning for allogeneic transplantation: mature follow-up from a large single-center cohort

Allogeneic transplantation using TLI-ATG conditioning for Hodgkin lymphoma after failure of autologous transplantation

Outcomes of hematopoietic cell transplantation for transformed follicular lymphoma

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