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ATLANTA—One of the largest single-center studies of fludarabine/melphalan-based allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients with myelofibrosis (MF) shows excellent overall survival (OS) with a low risk of relapse, according to investigators.
Allo-HSCT is the only potential curative treatment modality for MF.
However, it is associated with risks of transplant-related morbidity and mortality from graft-versus-host disease (GVHD), infection, graft rejection, and regimen-related toxicities.
This necessitates careful patient selection and intense peri-transplant management, said study investigator Haris Ali, MD, of the City of Hope Medical Center in Duarte, California.
He noted that there has been a 5-fold increase in allo-HSCT in the last 2 decades, mainly among older patients, due to the increase in reduced-intensity conditioning.
At the 2017 ASH Annual Meeting (in abstract 199), Dr Ali reported on a cohort of 110 MF patients who underwent allo-HSCT with fludarabine/melphalan conditioning at City of Hope between 2004 and 2017.
The patients, 58 with primary MF and 52 with secondary MF, were without prior acute leukemic transformation. They were a median age of 58.5 at the time of transplant, with a median interval of 15.2 months from MF diagnosis.
Virtually all (n=107) received peripheral blood stem cells, and 3 were transplanted with bone marrow as the stem cell source. Forty-nine allo-HSCT donors were matched related, 32 were matched unrelated, 27 were mismatched unrelated, 1 was mismatched relative, and 1 was haploidentical family.
Three-quarters of the patients had intermediate-2 or high-risk disease. Of the 110 patients, 16 had splenectomy prior to allo-HSCT. All but 2 patients engrafted.
After a median follow-up of 56.8 months, the 2-year OS rate was 74%, and the 5-year OS rate was 65%.
Non-relapse mortality at 2 years was 12%. At 5 years, it was 24%.
“The risk of non-relapse mortality was acceptable, considering the relatively older age of a large subset of patients; nearly half were over age 60 at allo-HSCT,” Dr Ali said.
In a univariate analysis, mismatched donors and matched unrelated donors were significantly associated with worse OS compared with matched related donors.
The cumulative incidence of relapse was 17% at 2 years and 5 years.
Splenectomy prior to transplant was associated with higher relapse risk, Dr Ali noted.
“Cytogenetic abnormalities were not associated with transplant relapse or other outcomes in our cohort,” he added.
Mutational changes are being tested in pre-transplant samples and will be reported at a later date.
The incidence of grade 2-4 and 3-4 acute GVHD at 100 days was 45% and 17%, respectively.
At 36 months, the cumulative incidence of all chronic GVHD was 66%. For extensive chronic GVHD, it was 59%.
“Interestingly, prior use of ruxolitinib increased the risk of grade 3-4 acute GVHD, possibly due to known inflammatory cytokine rebound,” Dr Ali said.
Extended use of ruxolitinib until day 30 or longer is currently being evaluated in a prospective trial at City of Hope (NCT02917096).
Dr Ali disclosed consulting fees from Incyte. 
ATLANTA—One of the largest single-center studies of fludarabine/melphalan-based allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients with myelofibrosis (MF) shows excellent overall survival (OS) with a low risk of relapse, according to investigators.
Allo-HSCT is the only potential curative treatment modality for MF.
However, it is associated with risks of transplant-related morbidity and mortality from graft-versus-host disease (GVHD), infection, graft rejection, and regimen-related toxicities.
This necessitates careful patient selection and intense peri-transplant management, said study investigator Haris Ali, MD, of the City of Hope Medical Center in Duarte, California.
He noted that there has been a 5-fold increase in allo-HSCT in the last 2 decades, mainly among older patients, due to the increase in reduced-intensity conditioning.
At the 2017 ASH Annual Meeting (in abstract 199), Dr Ali reported on a cohort of 110 MF patients who underwent allo-HSCT with fludarabine/melphalan conditioning at City of Hope between 2004 and 2017.
The patients, 58 with primary MF and 52 with secondary MF, were without prior acute leukemic transformation. They were a median age of 58.5 at the time of transplant, with a median interval of 15.2 months from MF diagnosis.
Virtually all (n=107) received peripheral blood stem cells, and 3 were transplanted with bone marrow as the stem cell source. Forty-nine allo-HSCT donors were matched related, 32 were matched unrelated, 27 were mismatched unrelated, 1 was mismatched relative, and 1 was haploidentical family.
Three-quarters of the patients had intermediate-2 or high-risk disease. Of the 110 patients, 16 had splenectomy prior to allo-HSCT. All but 2 patients engrafted.
After a median follow-up of 56.8 months, the 2-year OS rate was 74%, and the 5-year OS rate was 65%.
Non-relapse mortality at 2 years was 12%. At 5 years, it was 24%.
“The risk of non-relapse mortality was acceptable, considering the relatively older age of a large subset of patients; nearly half were over age 60 at allo-HSCT,” Dr Ali said.
In a univariate analysis, mismatched donors and matched unrelated donors were significantly associated with worse OS compared with matched related donors.
The cumulative incidence of relapse was 17% at 2 years and 5 years.
Splenectomy prior to transplant was associated with higher relapse risk, Dr Ali noted.
“Cytogenetic abnormalities were not associated with transplant relapse or other outcomes in our cohort,” he added.
Mutational changes are being tested in pre-transplant samples and will be reported at a later date.
The incidence of grade 2-4 and 3-4 acute GVHD at 100 days was 45% and 17%, respectively.
At 36 months, the cumulative incidence of all chronic GVHD was 66%. For extensive chronic GVHD, it was 59%.
“Interestingly, prior use of ruxolitinib increased the risk of grade 3-4 acute GVHD, possibly due to known inflammatory cytokine rebound,” Dr Ali said.
Extended use of ruxolitinib until day 30 or longer is currently being evaluated in a prospective trial at City of Hope (NCT02917096).
Dr Ali disclosed consulting fees from Incyte.
ATLANTA—One of the largest single-center studies of fludarabine/melphalan-based allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients with myelofibrosis (MF) shows excellent overall survival (OS) with a low risk of relapse, according to investigators.
Allo-HSCT is the only potential curative treatment modality for MF.
However, it is associated with risks of transplant-related morbidity and mortality from graft-versus-host disease (GVHD), infection, graft rejection, and regimen-related toxicities.
This necessitates careful patient selection and intense peri-transplant management, said study investigator Haris Ali, MD, of the City of Hope Medical Center in Duarte, California.
He noted that there has been a 5-fold increase in allo-HSCT in the last 2 decades, mainly among older patients, due to the increase in reduced-intensity conditioning.
At the 2017 ASH Annual Meeting (in abstract 199), Dr Ali reported on a cohort of 110 MF patients who underwent allo-HSCT with fludarabine/melphalan conditioning at City of Hope between 2004 and 2017.
The patients, 58 with primary MF and 52 with secondary MF, were without prior acute leukemic transformation. They were a median age of 58.5 at the time of transplant, with a median interval of 15.2 months from MF diagnosis.
Virtually all (n=107) received peripheral blood stem cells, and 3 were transplanted with bone marrow as the stem cell source. Forty-nine allo-HSCT donors were matched related, 32 were matched unrelated, 27 were mismatched unrelated, 1 was mismatched relative, and 1 was haploidentical family.
Three-quarters of the patients had intermediate-2 or high-risk disease. Of the 110 patients, 16 had splenectomy prior to allo-HSCT. All but 2 patients engrafted.
After a median follow-up of 56.8 months, the 2-year OS rate was 74%, and the 5-year OS rate was 65%.
Non-relapse mortality at 2 years was 12%. At 5 years, it was 24%.
“The risk of non-relapse mortality was acceptable, considering the relatively older age of a large subset of patients; nearly half were over age 60 at allo-HSCT,” Dr Ali said.
In a univariate analysis, mismatched donors and matched unrelated donors were significantly associated with worse OS compared with matched related donors.
The cumulative incidence of relapse was 17% at 2 years and 5 years.
Splenectomy prior to transplant was associated with higher relapse risk, Dr Ali noted.
“Cytogenetic abnormalities were not associated with transplant relapse or other outcomes in our cohort,” he added.
Mutational changes are being tested in pre-transplant samples and will be reported at a later date.
The incidence of grade 2-4 and 3-4 acute GVHD at 100 days was 45% and 17%, respectively.
At 36 months, the cumulative incidence of all chronic GVHD was 66%. For extensive chronic GVHD, it was 59%.
“Interestingly, prior use of ruxolitinib increased the risk of grade 3-4 acute GVHD, possibly due to known inflammatory cytokine rebound,” Dr Ali said.
Extended use of ruxolitinib until day 30 or longer is currently being evaluated in a prospective trial at City of Hope (NCT02917096).
Dr Ali disclosed consulting fees from Incyte.