Prognostic Model Could Help Predict Survival Outcomes for Patients With Myelofibrosis Undergoing AlloHCT

Roni Tamari, MD

A predictive system developed using data from United States and European stem cell transplant registries was prognostic of survival in patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation (alloHCT), according to data from a retrospective study published in Blood Advances.

United States patients with myelofibrosis who underwent allogeneic hematopoietic cell transplantation from an HLA-matched related/unrelated donor or unrelated HLA-mismatched donor and had data available from the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2000 to 2016 were included in the study (n = 623). Then, investigators assigned a weighted score using these factors to a cohort of patients who received a transplant in Europe (European Bone Marrow Transplant [EBMT] cohort; n = 623).

Study authors created the prognostic scoring system after a Cox multivariable model was used to identify factors prognostic of mortality. An age of more than 50 years (HR, 1.39; 95% CI, 0.98-1.96) and an HLA-matched unrelated donor (HR, 1.29; 95% CI, 0.98-1.7) were associated with an increased risk of death and were each assigned 1 point. Hemoglobin levels less than 100 g/L at the time of transplantation (HR, 1.63; 95% CI, 1.2-2.19) and a mismatched unrelated donor (HR, 1.78; 95% CI, 1.25-2.52) were also found to be related to an increased risk of death, and these were each worth 2 points. Patients with 1 to 2 points were deemed to have a low score, 3 to 4 points was an intermediate score, and 5 points was a high score.

At 3 years, the overall survival (OS) rate for the CIBMTR cohort was 69% (95% CI, 61%-76%) for patients with a low score, 51% (95% CI, 46%-56.4%) for those with an intermediate score, and 34% (95% CI, 21%-49%) for those with a high score (P < .001). Using the low-risk group as reference, the intermediate-risk group had a HR of 1.64 (95% CI, 1.23-2.18), and the high-risk group had an HR of 2.65 (95% CI, 1.70-4.14; overall P = .0002).

“Increasing score was predictive of increased transplant-related mortality [TRM; P = .0017] but not of relapse [P = .12],” lead study author Roni Tamari, MD, and colleagues wrote. Tamari is an assistant attending physician and bone marrow transplant specialist at Memorial Sloan Kettering Cancer Center in New York, New York.

Additionally, the 3-category system was predictive for disease-free survival (DFS) in the intermediate-risk group (HR, 1.44; 95% CI, 1.14-1.81) and high-risk group (HR, 1.83; 95% CI, 1.24-2.71; overall P = .0015). It was also predictive for TRM in the intermediate-risk group (HR, 1.63; 95% CI, 1.10-2.44) and high-risk group (HR, 3.09 (95% CI, 1.75-5.48; overall P = .0017).

In the EBMT cohort, the 3-category system was prognostic of OS (P = .0011), DFS (P = .0007), and TRM (P = .0021), but it was not predictive of relapse (P = .1673).

The study included data from patients at least 40 years of age with myelofibrosis who underwent alloHCT. Patients were excluded if they underwent syngeneic umbilical cord blood or mismatched related-donor transplantation, had graft-versus-host disease (GVHD) prophylaxis by ex vivo T-cell depletion or CD34-positive selection procedure, or unknown GVHD prophylaxis. Additionally, those with donor data, diagnosis date, or complete 100-day follow-up data missing were excluded.

Patients in the CIBMTR and EBMT cohorts had a median age of 54 years (range, 40-75) and 52 years (range, 40-74) at diagnosis, respectively, and were mostly males (63% and 68%). Before alloHCT, Karnofsky performance status scores were between 90 and 100 in 60% and 50% of patients, respectively. At diagnosis, patients in the CIBMTR and EBMT cohorts had myelofibrosis (87% and 80%), polycythemia vera (5% and 8%), essential thrombocythemia (8% and 8%), and polycythemia vera/essential thrombocythemia (0% and 3%). Spleen status was normal (21% and 13%), splenomegaly (72% and 49%), or splenectomy (4% and 14%), and patients had received 0 (24% and 37%), 1 (41% and 20%), 2 (17% vand3%), or at least 3 (16% and 3%) prior lines of pretreatments. JAK2 mutations were present in 32% and 34% of patients, respectively, and the rates of patients who received ruxolitinib (Jakafi) were 28% and 14%, respectively.

Patients in the CIBMTR cohort had a Dynamic International Prognostic Scoring System score before alloHCT of low (12%), intermediate-1 (45%) intermediate-2 (38%), or high (2%). Cytogenetics were either normal (40%), other (18%), unfavorable (18%), or not tested (5%).

The median time from diagnosis was 18 months (range, 2-294) and 26 months (range, 2-268) in the CIBMTR and EBMT cohorts, respectively. Donors included an HLA-identical sibling (35% and 75%), well-matched unrelated donor (52% and 17%), and partially matched unrelated donor (13% and 8%). Sex matches of donor and recipient were male to male (41% and 41%), male to female (22% and 27%), female to male (22% and 17%), and female to female (15% and 15%), respectively. Additionally, patients received a graft from peripheral blood (89% and 90%), did not receive total body irradiation (84% and 85%), and received myeloablative (46% and 29%), reduced intensity (47% vs 71%), or nonmyeloablative (6% vs 0%) conditioning regimens.

At diagnosis, patients in the CIBMTR and EBMT cohorts had blast in peripheral blood of greater than 1% (14% and 17%), a hemoglobin level of greater than 100 g/L (35% and 34%), a white blood cell count greater than 25 × 109 /L (9% and 8%), a platelet count of 50 × 109 /L to 100 × 109 /L (13% and 14%), and constitutional symptoms (29% and 28%), respectively.

Before alloHCT, patients in the CIBMTR and EBMT cohorts had blast in peripheral blood of greater than 1% (30% and 32%), a hemoglobin level of greater than 100 g/L (71% and 66%), a white blood cell count greater than 25 × 109 /L (13% and 15%), a platelet count of 50 × 109 /L to 100 × 109 /L (21% and 17%), and constitutional symptoms (17% and 29%), respectively.

In the CIMBTR cohort, the 1-, 3-, and 5-year OS rates were 65.7% (95% CI, 61.9%-69.4%), 54.6% (95% CI, 50.4%-58.7%), and 49.9% (95% CI, 45.5%-54.3%), respectively. TRM rates at 1, 3, and 5 years were 20.6% (95% CI, 17.4%-23.9%), 24.7% (95% CI, 21.3%-28.3%), and 27.1% (95% CI, 23.5%-31.0%), respectively.

Additionally, the 1-, 3-, and 5-year DFS rates were 39.7% (95% CI, 35.7%-43.7%), 31.1% (95% CI, 27.3%-34.9%), and 26.5% (95% CI, 22.7%-30.5%), respectively. The relapse rates at 1, 3, and 5 years were 39.7% (95% CI, 35.8- 43.6), 44.2% (95% CI, 40.2-48.3), and 46.3% (95% CI, 42.2- 50.5), respectively.

In the EBMT cohort, the 1-, 3-, and 5-year OS rates were 68.6% (95% CI, 64.9%-72.2%), 55.0% (95% CI, 51.0%-58.9%), and 51.2% (95% CI, 47.1-55.2), respectively. The 3-year TRM rate was 27.9% (95% CI, 24.4%-31.6%), and the 3-year relapse rate was 24.3% (95% CI, 20.9%-27.8%).

Study authors noted that a limitation of the study was that it included patients treated over a long time period, and between 2000 to 2016, changes and advances were made in the field of stem cell transplantation.

“The proposed system was prognostic of survival in 2 large cohorts, CIBMTR and EBMT, and can easily be applied by clinicians consulting patients with myelofibrosis about the transplantation outcomes,” study authors concluded.

Reference

Tamari R, McLornan DP, Ahn KW, et al. A simple prognostic system in patients with myelofibrosis undergoing allogeneic stem cell transplantation: a CIBMTR/EBMT analysis. Blood Adv. 2023;7(15):3993-4002. doi:10.1182/bloodadvances.2023009886

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