Li, Chin Y.

Abstract BACKGROUND: Splenectomy is performed for palliating symptoms in patients with primary myelofibrosis (PMF; as well as post essential thrombocythemia myelofibrosis/ post polycythemia myelofibrosis (Mesa et. al. Cancer2006;107(2):361–70). Pre-operative computed tomograms (CTs) of the spleen are frequently performed for estimating spleen size and anatomy, but sometimes raise concern over radiographic splenic masses. We performed a retrospective analysis of splenectomized PMF patients to determine the predictive value of CT in these patients. METHODS: Splenectomized patients, with confirmed PMF (and POST ET/PV MF), with an available pre-operative CT scan were included. Pre-operative CT scans were reviewed in a blinded fashion by a radiologist (B.B.), and histopathology was concurrently reviewed in a blinded fashion by a hematopathologist (C.Y.L.), with attention for radiographic evidence of splenic masses, splenic infarction and hemorrhage, evidence of extra-splenic masses. Additionally splenic volume was calculated by CT through an algorithm using maximal splenic length, width, and slice size (prorated ellipsoid where volume = (30+.58(XxYxZ)). Results from each review were compared and analyzed against clinical outcomes and documented splenic mass. RESULTS: Thirty-eight patients had concurrent CT and splenic pathology available underwent splenectomy for myelofibrosis (20 PMF; median age at diagnosis 64.6 years (range (46–79), 52% males). Splenic volume estimations by CT correlated well with splenic mass measurements. Splenic volume estimation by CT was 2365 CC (range 736–11355 CC), compared with a measured median splenic mass of 2000 mg (range 730–11750 mg) (bivariate analysis p<0.001). Splenic lesions were identified in a total of 33 patients (87%), 10 only by histopathology (30%), 3 only by CT (9%), and 20 by both (61%). Histopathologically 15 patients had localized hemorrhage, 13 had splenic infractions, and 8 had nodular foci of extramedullary hematopoiesis. Only 2 patients had evidence of an alternative malignancy (concurrent chronic lymphocytic leukemia (CLL, n =1) or systemic mast cell disease (n = 1). CT was very sensitive for detecting focal low density lesions (LDLs), which are roughly spherical regions of decreased contrast enhancement in the spleen, and detected the majority of macroscopic lesions. The presence of splenic infarctions histologically was associated with decreased post splenectomy survival (p=0.02; median 7.2 months vs. 15.0 months), however the sensitive (but not specific) presence of LDL lesions by CT did not have prognostic significance. The CT appearance of splenic hemorrhage was nonspecific, and since these areas of parenchymal hemorrhage were likely subacute/chronic, they could not be reliably distinguished from other LDLs. CONCLUSIONS: Pre-operative CT in patients whom undergo palliative splenectomy for myelofibrosis is a sensitive tool for determining the presence of small splenic lesions (hemorrhage, infarction and EMH). Additionally splenic volume estimation by CT, correlates well with measured splenic mass and may assist in operative planning. Splenic lesions in PMF (post ET/PV MF) by CT rarely represented an alternative malignant process, and should likely not be the sole indication for splenectomy. Splenic infarctions were associated with decreased survival after splenectomy, however CT is not always able to distinguish these lesions from EMH and hemorrhage.

Abstract Background It is widely recognized that advanced age and prior thrombosis predict recurrent thrombosis in essential thrombocythemia (ET) and are used to risk-stratify patients. However, the paucity of large sample size and long-term follow-up has limited the development of similar prognostic models for survival and leukemic transformation (LT). Methods Data was abstracted from the medical records of a consecutive cohort of patients with WHO-defined ET seen at the Mayo Clinic. Cox proportional hazards was used to determine the impact of clinical and laboratory variables on survival and LT. Overall survival and leukemia-free survival was estimated by Kaplan-Meier plots. Results i. Patient characteristics and outcome The study cohort included 605 patients of which 399 (66%) were females (median age, 57 years; range 5–91). Median follow-up was 84 months (range; 0–424). During this period, 155 patients (26%) have died and LT was documented in 20 patients (3.3%) occurring at a median of 138 months (range; 23–422) from ET diagnosis. ii. Prognostic variables for overall survival Univariate analysis of parameters at diagnosis identified age ≥ 60 years, hemoglobin less than normal (defined as < 12 g/dL in females and < 13.5 g/dL in males), leukocyte count ≥ 15 x 109/L, tobacco use, diabetes mellitus, thrombosis, male sex, and the absence of microvascular symptoms as independent predictors of inferior survival. All of the above except the last two (i.e. male sex and the absence of microvascular symptoms) sustained their prognostic significance on multivariate analysis. Based on the first three prognostic variables: age, hemoglobin level, and leukocyte count, we constructed a prognostic model for survival: low-risk (none of the risk factors), intermediate-risk (1of 3 risk factors), and high-risk (≥ 2 risk factors). The respective median survivals were 278, 200, and 111 months (p<0.0001; Figure 1) iii. Prognostic variables for leukemic transformation On univariate analysis of parameters at ET diagnosis, LT was significantly associated with platelet count ≥ 1000 x 109/L, hemoglobin less than normal, and exposure to P-32. However, on multivariate analysis, only hemoglobin less than normal and platelet count ≥ 1000 x 109/L maintained independent prognostic value. Accordingly, we utilized these two variables, to construct a prognostic model for LT: low-risk (none of the risk factors), intermediate-risk (1 risk factor), and high-risk (both risk factors). Only 1 of the 239 patients (0.4%) in the low-risk group vs. 14 of the 289 (4.8%) in the intermediate-risk and 5 of the 77 (6.5%) in the high-risk group underwent LT (p=0.0009; Figure 2). Conclusion The current study provides clinician-friendly prognostic models for both survival and LT in ET. Figure 1 Figure 1. Figure 2 Figure 2.

Abstract Background: Young (age < 60 years) patients with agnogenic myeloid metaplasia (AMM) are potential candidates for curative therapy with allogeneic stem cell transplantation. In such transplant-eligible patients, median overall survival (OS) is reported to be between 78 and 128 months. Because clinical course in an individual patients is markedly heterogeneous (survival ranges of months to decades), objective prognostic variables are essential for transplant decision making. Accordingly, we recently developed a modified Dupriez prognostic scoring system (PSS) that effectively discriminated between high (2 or more risk factors), intermediate (one risk factor) and low (no risk factor) risk patient groups based on the presence or absence of complete blood count (CBC)-derived adverse parameters; hemoglobin < 10 g/dl, leukocyte count < 4 or > 30 × 109/L, and platelet count < 100 × 109/L (Dingli et al. Cancer2006;106:623). In the current study, we identify absolute monocytosis of ≥ 1 × 109/L as an additional independent risk factor for survival in AMM. Methods: A consecutive cohort of WHO-defined AMM patients diagnosed before the age of 60 years was identified. The impact of various clinical and laboratory parameters on overall survival was evaluated with univariate and multivariable analysis. Results: The study included 129 patients (median age 52 years, range 18–60; 69 males) with AMM. An overall median survival of 75 months was univariately affected by platelet count < 100 × 109/L, hemoglobin level of < 10 g/dL, leukocyte count of either < 4 or > 30 × 109/L, monocytosis of ≥ 1 × 109/L, and, where cytogenetic studies were available (n=41), presence of unfavorable cytogenetic abnormalities (p < 0.01 in each instance). On multivariable analysis, all but leukocyte count maintained their significance. The independent prognostic value of monocyte count was also validated against the modified Dupriez score (see above) and thus allowed further refinement of the particular CBC-based PSS that included monocytosis of ≥ 1 × 109/L as a fourth risk factor; low-risk identified patients with none of the 4 risk factors, intermediate-risk with one risk factor, and high-risk with 2 or more risk factors (Figure 1). For comparison, Figure 2 illustrates survival curves according to the original Dupriez PSS. Conclusion: Monocytosis of ≥ 1 × 109/L is an independent risk factor for inferior survival in AMM. Figure 1. Mayo score Figure 1. Mayo score Figure 2. Dupriez score Figure 2. Dupriez score