Page 1301 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 70 Primary Myelofibrosis 1147

1.0 1.0
0.9 0.9
0.8 0.8
Propoirtion surviving 0.6 Sib PMF (n = 14, 4 dead) Propoirtion surviving 0.6 Sib HLA matched* (n = 32, 8 dead)
0.7
0.7
Sib ET-MF and PV-MF (n = 18, 4 dead)
Unrel HLA mismatched (n = 9, 7 dead)
0.5
0.5
Unrel PMF (n = 25, 16 dead)
Unrel HLA matched (n = 25, 16 dead)
Unrel ET-MF and PV-MF (n = 9, 7 dead)
0.4
0.4
0.3
0.2 0.3
0.2
0.1 0.1
0 6 12 18 24 30 36 42 48 54 60 66 72 78 0 6 12 18 24 30 36 42 48 54 60 66 72 78
A Months B Months

Sib Jak2V617F NEG (n = 17, 4 dead)
1.0 1.0
Sib Jak2V617F POS (n = 12, 4 dead)
0.9 Unrel Jak2V617F NEG (n = 19, 9 dead) 0.9
Unrel Jak2V617F POS (n = 18, 14 dead)
0.8 0.8
Propoirtion surviving 0.6 Propoirtion surviving 0.6 Sib age < 57 (n = 23, 5 dead)
0.7
0.7
Sib age ≥ 57 (n = 9, 3 dead)
0.5
0.5
Unrel age < 57 (n = 18, 12 dead)
Unrel age ≥ 57 (n = 16, 11 dead)
0.4
0.4
0.3
0.2
0.2 0.3
0.1 0.1
0 6 12 18 24 30 36 42 48 54 60 66 72 78 0 6 12 18 24 30 36 42 48 54 60 66 72 78
C Months D Months
Fig. 70.12 Survival for patients with myelofibrosis after receiving reduced-intensity allogeneic hematopoietic
stem cell transplantation was worse in the unrelated donor cohort compared with the related donor cohort
irrespective of diagnosis subtype, degree of HLA matching, JAK2 mutational status, and age. Final results from
the multicenter phase II MPD-RC 101 trial. ET-MF, essential thrombocythemia myelofibrosis; HLA, human
leukocyte antigen; NEG, negative; PMF, primary myelofibrosis; POS, positive; PV-MF, polycythemia vera
myelofibrosis. (Data from Rondelli et al: MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic
stem cell transplantation in patients with myelofibrosis. Blood 124:1183, 2014.)

Algorithm for Selection of Appropriate Patients for Stem Cell months of treatment, and grade 3/4 myelosuppression was seen in
Transplantation Stratified According to Risk Status 29% of patients, requiring dose reduction in 47% of the cases.
Interestingly, there was no difference in global hypomethylation
between responders and nonresponders. This finding could argue that
PMF <65 years of age the mechanism of action of this drug in responding MF patients may
not be directly through induction of DNA promoter site demethyl-
ation. Studies designed to evaluate the methylation status of specific
Low risk Intermediate risk High risk genes thought to be silenced by this epigenetic modification (e.g.,
p15 INK4b and p16 INK4a ) need to be done in the future. A modified
5-day course of 5-azacitidine was also tested in a group of 10 MF
Observation − Discuss option with − If age <50 years, patients, and was found to have even less of a response rate than the
the patient. consider myeloablative/ full 7-day course. Case series highlight the potential role of decitabine
− If age <50 years, RIC transplantation in the treatment of MF in blast phase, and initial reports of subcu-
and sibling − If age >50 years, taneous low-dose decitabine in advanced MF also appears to hold
available, consider consider RIC promise and is currently being evaluated in larger studies. LBH589
myeloablative/RIC (panobinostat) is a potent pan-deacetylase inhibitor that has also been
transplantation evaluated in PMF patients in two separate trials with thrombocyto-
penia as the dose-limiting toxicity and the demonstration of a signal