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Article ; Online: Recent advances in allogeneic hematopoietic cell transplantation for acute myeloid leukemia.

Gomez-Arteaga, Alexandra / Gyurkocza, Boglarka

2020 Volume 27, Issue 2, Page(s) 115–121

Abstract: Purpose of review: Allogeneic hematopoietic cell transplantation (HCT), with associated graft-versus-leukemia effects, remains the best postremission strategy for patients with intermediate or high-risk acute myeloid leukemia (AML), with a curative ... ...

Abstract	Purpose of review: Allogeneic hematopoietic cell transplantation (HCT), with associated graft-versus-leukemia effects, remains the best postremission strategy for patients with intermediate or high-risk acute myeloid leukemia (AML), with a curative potential. Here, we highlight recent advances in allogeneic HCT that broadened access, refined prognostication, and improved outcomes of AML patients undergoing this procedure. Recent findings: Eligibility for allogeneic HCT continued to expand to AML patients older than 60 years, as well as to patients lacking human leukocyte antigen (HLA)-matched donors with the advent of alternative donor sources, such as umbilical cord blood and HLA-haploidentical transplantation. Molecular profiling of AML has redefined prognostication for patients in specific AML genomic subgroups undergoing allogeneic HCT and has served as a new strategy for measuring minimal residual disease before and after allogeneic HCT. Using high intensity conditioning regimens has emerged as a potential strategy to reduce risk of relapse and improve overall survival, especially in patients with minimal residual disease prior to allogeneic HCT. Summary: As access to allogeneic HCT continues to improve, also, with more refined prognostic strategies, the field continues to move to optimize transplantation approaches by decreasing the risk of relapse and minimizing transplant-related complications.
MeSH term(s)	Hematopoietic Stem Cell Transplantation/methods ; Humans ; Leukemia, Myeloid, Acute/surgery ; Transplantation Conditioning/methods
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000572
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Article ; Online: Racial/ ethnic disparities in availability of volunteer unrelated donors for allogeneic transplantation.

Fingrut, Warren B / Davis, Eric / Archer, Anne / Brown, Samantha / Devlin, Sean M / Nhaissi, Melissa / Rapoport, Candice / Chinapen, Stephanie / Kelly, Amanda / Wells, Deborah S / Scaradavou, Andromachi / Gyurkocza, Boglarka / Papadopoulos, Esperanza B / Politikos, Ioannis / Shaffer, Brian C / Barker, Juliet

Blood advances

2024

Abstract: Despite the global unrelated donor (URD) registry size, the degree to which URD availability is a transplant barrier is not established. We evaluated the availability of 3,843 URDs requested for 455 diverse adult patients (predominantly with acute ... ...

Abstract	Despite the global unrelated donor (URD) registry size, the degree to which URD availability is a transplant barrier is not established. We evaluated the availability of 3,843 URDs requested for 455 diverse adult patients (predominantly with acute leukemia). URDs for non-Europeans were more likely to be domestic and had markedly lower Donor Readiness Scores. Of URDs requested for confirmatory HLA-typing (CT) alone (i.e. without simultaneous workup), 1,894/3,529 (54%) were available. Availability of domestic URDs was 45%. Donor Readiness Score was highly predictive of CT availability. Compared with Europeans (n=335), more non-European patients (n=120) had >10 URDs requested and <5 available. Of workup requests (after CT or CT-workup), <70% (604/889, 68%) were available. More non-Europeans had <2 URDs available. URD availability for CT was markedly worse for non-Europeans, with availabilities for African, non-Black Hispanic, and Asian patients of 150/458 (33%), 120/258 (47%) and 119/270 (44%), respectively, with further decrements in URD workup availability. Our data suggest the functional size of the URD pool is much smaller than appreciated, mandating major operational changes for transplant Centers and donor registries. Likelihood of donor availability should have a high priority in donor selection. Considering patient ancestry and URD Donor Readiness Scores, Centers should pursue, and registries permit, simultaneous pursuit of many URDs, and abandon futile searches. Patients should be informed about their likelihood of donor availability and alternative options. Finally, while registries should address high URD attrition and speed procurement, use of all HLA-disparate graft types is needed to facilitate timely transplantation for all.
Language	English
Publishing date	2024-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023012385
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Article ; Online: Outcomes of relapsed B-cell acute lymphoblastic leukemia after sequential treatment with blinatumomab and inotuzumab.

Wudhikarn, Kitsada / King, Amber C / Geyer, Mark B / Roshal, Mikhail / Bernal, Yvette / Gyurkocza, Boglarka / Perales, Miguel-Angel / Park, Jae H

Blood advances

2022 Volume 6, Issue 5, Page(s) 1432–1443

Abstract: Novel monoclonal antibody (mAb)-based therapies targeting CD19 and CD22 (blinatumomab and inotuzumab) have shown high rates of complete remission (CR) and been used as a bridging treatment to potentially curative allogeneic hematopoietic stem cell ... ...

Abstract	Novel monoclonal antibody (mAb)-based therapies targeting CD19 and CD22 (blinatumomab and inotuzumab) have shown high rates of complete remission (CR) and been used as a bridging treatment to potentially curative allogeneic hematopoietic stem cell transplantation (alloHSCT) in adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, limited data exist on the outcome of patients resistant to both mAbs as well as responses to each agent when progressed after the alternate antigen-targeted mAb. Herein, we report outcomes of 29 patients with R/R B-ALL previously treated with both blinatumomab and inotuzumab. Twenty-five patients (86.2%) received blinatumomab as first mAb (mAb1), and CD19-negative/dim relapses were observed in 44% of the patients. Inotuzumab induced CR in 68% of the patients for post-blinatumomab relapse regardless of CD19 expression status. The median time between mAb1 and mAb2 was 99 days. Twelve (63.2%) of 19 patients who achieved remission after mAb2 underwent alloHSCT. The median time from mAb2 to alloHSCT was 37.5 days. Acute graft-versus-host disease and nonrelapse mortality were observed in 58.3% (grade 3 or higher, 25%) and 41.7%, respectively. With a median follow-up of 16.8 months after mAb2, 19 patients (65.5%) relapsed, and 21 patients (72.4%) have died. Overall survival was not different between alloHSCT and non-alloHSCT patients. In conclusion, patients with B-ALL who relapsed after blinatumomab could be successfully rescued by inotuzumab as a bridge to alloHSCT but represent an ultra-high-risk group with poor overall survival. Further studies, including novel consolidation and treatment sequence, may improve outcomes of these patients.
MeSH term(s)	Adult ; Antibodies, Bispecific/adverse effects ; Antigens, CD19 ; Burkitt Lymphoma ; Humans ; Inotuzumab Ozogamicin ; Lymphoma, B-Cell ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Recurrence
Chemical Substances	Antibodies, Bispecific ; Antigens, CD19 ; blinatumomab (4FR53SIF3A) ; Inotuzumab Ozogamicin (P93RUU11P7)
Language	English
Publishing date	2022-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021005978
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Article ; Online: CD34-selected allogeneic hematopoietic cell transplantation for chronic myeloid leukemia in the tyrosine kinase era.

Vaughn, John L / Brown, Samantha / Papadopoulos, Esperanza B / Jakubowski, Ann A / Tamari, Roni / Giralt, Sergio A / Ponce, Doris M / Cho, Christina / Perales, Miguel-Angel / Shaffer, Brian C / Gyurkocza, Boglarka

Bone marrow transplantation

2022 Volume 57, Issue 11, Page(s) 1740–1742

MeSH term(s)	Humans ; Protein-Tyrosine Kinases ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy ; Hematopoietic Stem Cell Transplantation ; Antigens, CD34 ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	Protein-Tyrosine Kinases (EC 2.7.10.1) ; Antigens, CD34 ; Protein Kinase Inhibitors
Language	English
Publishing date	2022-09-08
Publishing country	England
Document type	Letter
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/s41409-022-01783-7
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Article ; Online: Conditioning regimens for hematopoietic cell transplantation: one size does not fit all.

Gyurkocza, Boglarka / Sandmaier, Brenda M

Blood

2014 Volume 124, Issue 3, Page(s) 344–353

Abstract: An essential component of allogeneic and autologous hematopoietic cell transplantation (HCT) is the conditioning regimen administered before the hematopoietic cell infusion. Early regimens relied on dose intensity, assuming that high-dose ... ...

Abstract	An essential component of allogeneic and autologous hematopoietic cell transplantation (HCT) is the conditioning regimen administered before the hematopoietic cell infusion. Early regimens relied on dose intensity, assuming that high-dose chemoradiotherapy would eliminate malignant disease and reinfusion of the graft would then restore hematopoiesis. However, as the contribution of graft-versus-tumor effects to the success of allogeneic HCT was recognized over time, in an effort to exploit these, many investigators lowered the dose of radiation and chemotherapeutic agents in the preparative regimen. This resulted in a major paradigm shift, and consequently, the pool of eligible patients underwent a remarkable expansion. In this article, we provide a review of the definition of high-dose, reduced-intensity, and nonmyeloablative conditioning regimens, the most commonly used agents and combinations, and the evolution of some early regimens. We also provide a brief review of the toxicities associated with these regimens.
MeSH term(s)	Allografts ; Antilymphocyte Serum/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Autografts ; Clinical Trials as Topic ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cell Transplantation/trends ; Humans ; Myeloablative Agonists/therapeutic use ; Radioimmunotherapy ; Transplantation Conditioning/methods ; Transplantation Conditioning/trends ; Whole-Body Irradiation
Chemical Substances	Antilymphocyte Serum ; Myeloablative Agonists
Language	English
Publishing date	2014-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2014-02-514778
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Article ; Online: Second allogeneic hematopoietic cell transplantation for relapse after first allografts.

Gyurkocza, Boglarka / Storb, Rainer / Chauncey, Thomas R / Maloney, David G / Storer, Barry E / Sandmaier, Brenda M

Leukemia & lymphoma

2019 Volume 60, Issue 7, Page(s) 1758–1766

Abstract: We analyzed outcomes of 126 patients with hematologic malignancies, who relapsed after first allogeneic hematopoietic cell transplantation (HCT) and received subsequent allografts. In 17 cases, the original donors were utilized, while in 109 cases ... ...

Abstract	We analyzed outcomes of 126 patients with hematologic malignancies, who relapsed after first allogeneic hematopoietic cell transplantation (HCT) and received subsequent allografts. In 17 cases, the original donors were utilized, while in 109 cases different donors were identified. The 2-year overall survival (OS), relapse, and non-relapse mortality (NRM) rates were 33%, 42%, and 33%, respectively. Patients with early relapse after first allogeneic HCT (within 100 days vs. 100 days to 12 months vs. >12 months) had higher relapse rates (50% vs. 47% vs. 34%, respectively;
MeSH term(s)	Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Graft vs Host Disease/epidemiology ; Graft vs Host Disease/mortality ; Graft vs Host Disease/pathology ; Graft vs Host Disease/therapy ; Hematologic Neoplasms/mortality ; Hematologic Neoplasms/pathology ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation/mortality ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/therapy ; New York/epidemiology ; Prognosis ; Retrospective Studies ; Survival Rate ; Transplantation Conditioning ; Transplantation, Homologous ; Unrelated Donors ; Young Adult
Language	English
Publishing date	2019-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2018.1542149
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Article ; Online: Racial disparities in access to alternative donor allografts persist in the era of "donors for all".

Blood advances

2022 Volume 6, Issue 20, Page(s) 5625–5629

MeSH term(s)	Humans ; Tissue Donors ; Healthcare Disparities ; Transplantation, Homologous ; Allografts
Language	English
Publishing date	2022-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022007814
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Article ; Online: Reduced-Intensity Compared to Nonmyeloablative Conditioning in Patients with Non-Hodgkin Lymphoma Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Nath, Karthik / Peterson, Kristen / Brown, Samantha / Devlin, Sean / Rodriguez, Natasia / Barker, Juliet / Giralt, Sergio / Gyurkocza, Boglarka / Jakubowski, Ann / Papadopoulos, Esperanza / Ponce, Doris / Scordo, Michael / Shah, Gunjan / Perales, Miguel-Angel / Sauter, Craig / Lin, Andrew / Dahi, Parastoo B

Transplantation and cellular therapy

2023 Volume 30, Issue 1, Page(s) 81–92

Abstract: Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning are preferred for patients with non-Hodgkin lymphoma (NHL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). Although prior studies have suggested that ... ...

Abstract	Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning are preferred for patients with non-Hodgkin lymphoma (NHL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). Although prior studies have suggested that higher-intensity regimens in RIC-NMA conditioning are associated with inferior outcomes in patients with NHL, the optimal conditioning regimen remains unknown. We performed a retrospective single-center analysis to determine outcomes of adult patients with B cell and T cell NHL who underwent allo-HCT and received either RIC or NMA conditioning between March 2008 and December 2019. RIC regimens included fludarabine-cyclophosphamide-thiotepa-4 Gy-total body irradiation (Flu-Cy-TT-4Gy-TBI), fludarabine-melphalan (Flu-Mel), fludarabine-cyclophosphamide-4 Gy-total body irradiation (Flu-Cy-4Gy-TBI), and fludarabine-busulfan-4 (Flu-Bu-4). The NMA regimen comprised fludarabine-cyclophosphamide-2 Gy-total body irradiation (Flu-Cy-2Gy-TBI). The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), nonrelapse mortality (NRM), and the incidence of acute and chronic graft-versus-host-disease (GVHD). Of 279 transplants recipients (median age, 58 years), 110 received RIC (55% Flu-Mel, 38% Flu-Cy-TT-4Gy-TBI, 6% Flu-Bu-4, 1% Flu-Cy-4Gy-TBI) and 169 received NMA conditioning with Flu-Cy-2Gy-TBI. With a median of 64 months of follow-up post-allo-HCT, there was no significant difference in OS between the NMA and RIC groups (median, not reached [NR] versus 103 months; P = .1), and this was maintained on multivariable analysis. Similarly, after adjustment for all independently significant covariates (age, Karnofsky Performance Status [KPS], Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI], and disease histology), the regression analysis showed no significant difference in PFS with RIC compared to NMA conditioning (hazard ratio [HR] 1.38; 95% confidence interval [CI], .92 to 2.09; P = .24). On univariable analysis, there was no significant difference in NRM between the RIC and NMA arms (100-day estimate, 10.0% versus 1.8%; P = .5). After adjustment for age, ethnicity, KPS, HCT-CI, GVHD prophylaxis, and donor source, RIC conditioning was associated with a significantly higher incidence of NRM compared to NMA conditioning (HR, 2.61; 95% CI, 1.04 to 6.52; P = .039). On multivariable analysis, compared with the NMA arm, the RIC arm had higher rates of grade II-IV (HR, 2.25; 95% CI, 1.31 to 3.86; P = .002) and grade III-IV acute GVHD (HR, 5.62; 95% CI, 2.03 to 15.6; P < .001). The findings of this study suggest that NMA conditioning with Flu-Cy-TBI-2Gy may be considered over more intensive RIC regimens for patients with NHL undergoing allo-HCT.
MeSH term(s)	Adult ; Humans ; Middle Aged ; Retrospective Studies ; Transplantation, Homologous/adverse effects ; Survival Analysis ; Hematopoietic Stem Cell Transplantation/adverse effects ; Lymphoma, Non-Hodgkin/complications ; Lymphoma, Non-Hodgkin/drug therapy ; Cyclophosphamide/therapeutic use ; Graft vs Host Disease/epidemiology ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Busulfan/therapeutic use ; Thiotepa
Chemical Substances	Cyclophosphamide (8N3DW7272P) ; Busulfan (G1LN9045DK) ; Thiotepa (905Z5W3GKH)
Language	English
Publishing date	2023-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2023.09.022
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Zs.A 5082: Show issues

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Article ; Online: Prospective analysis to determine barriers to allogeneic hematopoietic cell transplantation in patients with acute leukemia.

American journal of hematology

2023 Volume 98, Issue 12, Page(s) 1869–1876

Abstract: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for patients with acute leukemia. Despite this, studies have shown that only a minority of patients ultimately proceed to allo-HCT. The primary objective of this ...

Abstract	Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for patients with acute leukemia. Despite this, studies have shown that only a minority of patients ultimately proceed to allo-HCT. The primary objective of this prospective, observational study was to identify the rate of allo-HCT in patients for whom it was recommended, and reasons why patients deemed appropriate and eligible for HCT did not subsequently undergo transplant. Between April 2016 and April 2021, adult patients with newly diagnosed or relapsed/refractory acute leukemia were enrolled at the time of induction/reinduction therapy. Initial transplantation workup and allo-HCT recommendations were made during the early phase of induction/reinduction. Of the 307 enrolled patients, allo-HCT was recommended to 85% (n = 259), of whom 66% (n = 170) underwent transplant. Donor sources comprised 54% human leukocyte antigen (HLA)-matched unrelated donors, 20% HLA-matched sibling donors and HLA-mismatched graft sources with 15% umbilical cord blood units, 8% HLA-mismatched unrelated donors, and 4% HLA-haploidentical donors. The most common reason for transplant disqualification in the 89 patients in whom it was initially recommended was persistent/relapsed disease (70%), followed by early patient death (10%). In this prospective study, we report a high allo-HCT rate, which may be due to early transplant referral and workup. The main allo-HCT barrier was disease control, followed by early patient death. With the increasing availability of HLA-mismatched graft sources, the lack of donor availability was not a transplant barrier. Further development of novel transplant strategies for patients not achieving remission and improvements in induction regimens could result in increased allo-HCT utilization.
MeSH term(s)	Adult ; Humans ; Prospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects ; Unrelated Donors ; Transplantation, Homologous ; Leukemia, Myeloid, Acute/therapy ; Leukemia, Myeloid, Acute/etiology ; Acute Disease ; HLA Antigens ; Graft vs Host Disease/etiology ; Retrospective Studies
Chemical Substances	HLA Antigens
Language	English
Publishing date	2023-09-09
Publishing country	United States
Document type	Observational Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.27084
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Article ; Online: The Simplified Comorbidity Index predicts non-relapse mortality in reduced-intensity conditioning allogeneic haematopoietic cell transplantation.

British journal of haematology

2023 Volume 203, Issue 5, Page(s) 840–851

Abstract: Comorbidity assessment before allogeneic haematopoietic cell transplantation (allo-HCT) is essential for estimating non-relapse mortality (NRM) risk. We previously developed the Simplified Comorbidity Index (SCI), which captures a small number of 'high- ... ...

Abstract	Comorbidity assessment before allogeneic haematopoietic cell transplantation (allo-HCT) is essential for estimating non-relapse mortality (NRM) risk. We previously developed the Simplified Comorbidity Index (SCI), which captures a small number of 'high-yield' comorbidities and older age. The SCI was predictive of NRM in myeloablative CD34-selected allo-HCT. Here, we evaluated the SCI in a single-centre cohort of 327 patients receiving reduced-intensity conditioning followed by unmanipulated allografts from HLA-matched donors. Among the SCI factors, age above 60, mild renal impairment, moderate pulmonary disease and cardiac disease were most frequent. SCI scores ranged from 0 to 8, with 39%, 20%, 20% and 21% having scores of 0-1, 2, 3 and ≥4 respectively. Corresponding cumulative incidences of 3-year NRM were 11%, 16%, 22% and 27%; p = 0.03. In multivariable models, higher SCI scores were associated with incremental risks of all-cause mortality and NRM. The SCI had an area under the receiver operating characteristic curve of 65.9%, 64.1% and 62.9% for predicting 1-, 2- and 3-year NRM versus 58.4%, 60.4% and 59.3% with the haematopoietic cell transplantation comorbidity index. These results demonstrate for the first time that the SCI is predictive of NRM in patients receiving allo-HCT from HLA-matched donors after reduced-intensity conditioning.
MeSH term(s)	Humans ; Comorbidity ; Hematopoietic Stem Cell Transplantation/methods ; Recurrence ; Retrospective Studies ; Tissue Donors ; Transplantation Conditioning/methods ; Transplantation, Homologous/methods ; Mortality
Language	English
Publishing date	2023-08-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19055
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