Abstract
BACKGROUND: Myelofibrosis with myeloid metaplasia (MMM) is a rare chronic myeloproliferative disease characterized by both myeloproliferative and myelodepletive features: myeloproliferation typically includes enhanced spontaneous mobilization of hematopoietic progenitor cells (HPC) from the bone marrow (BM) and their homing into extramedullary sites (mainly spleen); myelodepletion results from exhaustion of both BM and extramedullary hemopoiesis.
AIMS: To investigate the extent and distribution of hematopoiesis in MMM patients and to capture its relationship with BM fibrosis, HPC mobilization and clinical severity.
METHODS: Immunoscintigraphy employing a dual-head camera was performed 120–260 minutes (median 180 minutes) after administration of 553–830 MBq (median 700 MBq) 99mTc-BW250/183, corresponding to 0.3–0.5 mg. Hematopoietic function in the central compartment (sacrum) was described by “subtypes” (normal, increased or decreased) and by the sacrum-to-soft tissue uptake ratio (UR) (Huic at el, J Nucl Med 1997). The degree of peripheral BM displacement (limbs) was described through 5 “types” (I to V) (Huic at el, J Nucl Med 1997).
RESULTS: Twenty-three MMM patients (13 males, median age 55 years) were studied. Eleven patients showed a reduced uptake by the central BM compartment: they had a higher WHO fibrosis grade (p=0.008), lower hemoglobin values (p=0.012) and lower platelet counts (p=0.007) than patients with a preserved central compartment. Patients with an exhausted central compartment at immunoscintigraphy also showed a significantly higher mobilization of HPC into peripheral blood, as documented by higher values of the following parameters: CD34+ count (0.86% vs 0.12%; p=0.029), immature myeloid cells or blasts (9.5% versus 0.3%; p=0.005), spleen size (9.3 vs 2.4 centimeters from costal arc; p=0.007). Among the patients with a depressed central compartment, those who also lost peripheral BM function (type V) showed a more severe myelodepletion and more intense HPC mobilization. On the opposite side, among the 12 patients with a preserved central compartment, the 8 ones with a mild peripheral BM displacement (type I–II) showed absent or mild fibrosis (WHO 0-1), elevated platelet counts, normal to high hemoglobin values, minimally enlarged spleens and no hints of increased HPC mobilization (CD34+ <0.1%; no blasts; <=1% immature myeloid cells). From these data it appears that progressive fibrosis and exhaustion of central BM is accompanied by a gradual displacement of hemopoiesis into the peripheral bone compartment and the spleen and by derangement of HPC trafficking.
CONCLUSIONS: BM immunoscintigraphy accurately tracks MMM clinical features and may help staging MMM patients, understanding MMM biology and targeting therapies
Clinical and immunoscintigraphy parameters (means and ANOVA p values) Type I-III II–IV V p § Barosi et al, Leuk Lymph 2002 Subtype not reduced reduced reduced UR 9.39 2.53 1.22 0.041 Fibrosis (grade) 1.0 2.0 2.7 0.001 Hb (g/dl) 13.5 11.1 9.6 0.023 PLT *10(9) 613 283 86 0.04 WBC *10(9) 8.9 6.2 6.9 0.059 Spleen (cm) 1.9 7.6 10.5 0.011 Immature myeloid cells (%) 0.3 3.6 9.7 0.0005 Blast cells (%) 0.0 0.2 3.8 0.048 CD34+ cells (%/μl) 0.1 / 6.4 0.4 / 22.1 1.3 / 155.5 0.009 / 0.12 LDH (UI/l) 566 956 1381 0.014 Severity Score§ 2.4 3.0 3.8 0.036 Disease duration (mo) 43 30 74 0.45
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