JAK2-V617F–triggered preemptive and salvage adoptive immunotherapy with donor-lymphocyte infusion in patients with myelofibrosis after allogeneic stem cell transplantation

Kröger, Nicolaus; Alchalby, Haefaa; Klyuchnikov, Evgeny; Badbaran, Anita; Hildebrandt, York; Ayuk, Francis; Bacher, Ulrike; Böck, O.; Kvasnicka, Michael; Fehse, Boris; Zander, Axel R.

doi:10.1182/blood-2008-11-190975

Cited by 87 publications

(71 citation statements)

References 9 publications

(9 reference statements)

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“…It is well appreciated that hematopoietic recovery is faster in splenectomized patients. [19][20][21] Thus, pretreatment with ruxolitinib might actually facilitate both engraftment and hematological recovery after allogeneic HCT through the reduction in cytokine levels and splenomegaly.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib

Jaekel

Behre

Behning

et al. 2013

Bone Marrow Transplant

100

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The Janus-activated kinase 1 (JAK1) and JAK2 inhibitor ruxolitinib is effective in decreasing symptomatic splenomegaly and myelofibrosis (MF)-related symptoms. However, allogeneic hematopoietic cell transplantation (HCT) remains the only curative option. We evaluated the impact of ruxolitinib on the outcome after HCT. A cohort of 14 patients (median age 58 years) received a subsequent graft from related (n ¼ 3) and unrelated (n ¼ 11) donors after a median exposure of 6.5 months to ruxolitinib. At HCT, MF risk for survival according to the International Prognostic Scoring System was intermediate-2 or high risk in 86% of patients. Under ruxolitinib, MF-related symptoms were ameliorated in 10 (71.4%) patients and the palpable spleen reduced by a median of 41% in 7 (64%) of 11 patients with splenomegaly. Engraftment occurred in 13 (93%) patients. Acute GvHD grade-III occurred in 2 (14%) patients. Median follow-up was 9 months. Survival, EFS and treatment-related mortality were 78.6, 64 and 7%, respectively. Through the anti-JAK-mediated reduction in both cytokines and splenomegaly as well as improvement in performance status, ruxolitinib might improve outcome after allogeneic HCT in patients with MF. The downregulation of inflammatory cytokines might have a beneficial impact on graft failure and acute GvHD.

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Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib

Jaekel

Behre

Behning

et al. 2013

Bone Marrow Transplant

100

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“…Applying donor lymphocyte infusions at the stage of molecular relapse is more likely to be effective and less toxic than in the case of full-blown clinical relapse. 5 However, early interventions are only applicable in the presence of a reliable disease-specific molecular marker and a sensitive and feasible monitoring method. Mainly in the patients with primary MF (PMF) and essential thrombocythemia (ET) who lack JAK2 V617F, other mutations such as MPL W515L/K were detected in B5% of cases.…”

Section: Introductionmentioning

confidence: 99%

Screening and monitoring of MPL W515L mutation with real-time PCR in patients with myelofibrosis undergoing allogeneic-SCT

Alchalby

Badbaran

Böck

et al. 2010

Bone Marrow Transplant

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Monitoring of minimal residual disease (MRD) after allogeneic (allo)-SCT for myelofibrosis (MF) allows recognizing the depth of remission and thus guides application of appropriate therapeutic interventions. MPL W515L/K mutations, which are detected in 5-10% of JAK2V617F-negative patients, may be useful for this purpose. Using a highly sensitive quantitative PCR method, we tested 90 patients with MF who underwent allo-SCT for the presence of MPL W515L/K mutations. Two patients with primary MF were found to harbor MPLW515L while no patient was positive for MPLW515K mutation. Both patients were JAK2V617F negative and cleared the mutation rapidly after allo-SCT and remained negative for a median follow-up of 19 months. The results of molecular monitoring correlated well with other remission parameters such as normalization of peripheral blood counts and morphology and complete donor chimerism. We conclude that MPLW515L can be cleared after allo-SCT and hence may be used as an MRD marker in a proportion of JAK2V617F-negative MF patients.

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“…[7][8][9][10] Such approaches would improve the detection sensitivity above that of Sanger sequencing and potentially allow quantitation of mutation level. Both persistence and eradication of the CSF3R T618I described above, correlating with the clinical course in both patients, indicate that serial monitoring of CSF3R mutations in aCML patients undergoing allo-SCT is a useful adjunct in the assessment of transplant efficacy.…”

mentioning

confidence: 99%

The CSF3R T618I mutation as a disease-specific marker of atypical CML post allo-SCT

Langabeer

McCarron

Haslam

et al. 2014

Bone Marrow Transplant

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JAK2-V617F–triggered preemptive and salvage adoptive immunotherapy with donor-lymphocyte infusion in patients with myelofibrosis after allogeneic stem cell transplantation

Cited by 87 publications

References 9 publications

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib

Screening and monitoring of MPL W515L mutation with real-time PCR in patients with myelofibrosis undergoing allogeneic-SCT

The CSF3R T618I mutation as a disease-specific marker of atypical CML post allo-SCT

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