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504 Background: For PM patients (pts) with locally advanced ER+ HER2- BC, NET improves breast conservation surgery (BCS) rates, and modified preoperative endocrine prognostic index (mPEPI) 0, defined as pT1-2 pN0 Ki67< 2.7%, or pathologic complete response (pCR: no invasive disease in breast or lymph node) is associated with low risk of recurrence without adjuvant chemotherapy (CT). The ALTERNATE trial was initiated to assess if the endocrine-sensitive disease rate (ESDR: number of mPEPI 0 pts/number of eligible pts initiating NET) with fulvestrant (F) or F+anastrozole (A) is improved relative to A alone (reported here) and if the 5-year (yr) recurrence-free survival (RFS) rate for pts with mPEPI 0 on A alone without CT is ≥ 95% (awaits further follow-up). Methods: PM pts with clinical stage II/III ER+ HER2- BC were randomized 1:1:1 to 1 mg A po daily, 500 mg F IM every 4 week (wk)s after loading dose, or A+F for 6 months. Ki67 was tested centrally on biopsies acquired prior to NET, wk 4, wk 12 and at surgery. Pts with Ki67 >10% at wk 4 or 12 were recommended to go off protocol-directed ET and switch to CT. Pts with mPEPI 0 at surgery were recommended to continue assigned ET for 1.5 yrs followed by A for a total of 5 yrs ET (and not to receive CT). The primary endpoint of the neoadjuvant phase was ESDR. ESDR of each F arm was compared to that of the A alone arm. With 425 pts per arm, a one-tailed alpha = 0.025 chi-square test of two independent proportions has 84% power to detect an increase of ≥10% in ESDR for F or F+A compared to the A arm, assuming ESDR ≤30% in A. Results: 1362 pts (A 452; F 454; A+F 456) were enrolled Feb 2014 to Nov 2018. 63 pts were excluded (did not start NET). Of the remaining 1299 pts (A 434; F 431, A+F 434), 42% were cN1-3 and 73% were considered candidates for BCS. ESDR was 18.6% (95%CI: 15.1-22.7%) with A, 22.7% (95%CI: 18.9-27.0%) with F, and 20.5% (95%CI: 16.8-24.6%) with A+F. No significant difference in ESDR was found between A and F (p=0.15) or A and A+F (p=0.55). Among the 825 pts with wk 4 Ki67 < 10% who completed NET and surgery, ESDR and the BCS rate were 27.7% and 70.3% with A; 29.6% and 68.1% with F, and 26.8% and 69.9% with A+F, respectively. Conclusion: Neither F nor F+A significantly improved ESDR compared to A alone in PM pts with locally advanced ER+ HER2- BC. RFS data are awaited. Support: U10CA180821, U10CA180882, U24CA196171, https://acknowledgments.alliancefound.org ; NCI BIQSFP, BCRF, Genentech, AstraZeneca. Clinical trial information: NCT01953588 .

Management of PD-1 blockade resistance in metastatic melanoma (MM) remains challenging. Immunotherapy or chemotherapy alone provides limited benefit in this setting. Chemo-immunotherapy (CIT) has demonstrated favorable efficacy and safety profiles in lung cancer. Our pre-clinical study showed that in MM patients who have failed PD-1 blockade, the addition of chemotherapy increases CX3CR1+ therapy-responsive CD8+ T-cells with enhanced anti-tumor activity, resulting in improved clinical response. Here, we examined the clinical outcomes of CIT in MM patients after PD-1 blockade failure and the treatment-related changes in CX3CR1+ therapy-responsive CD8+ T-cells. We reviewed MM patients seen between January 2012 and June 2018 who failed anti-PD-1-based therapy and received subsequent CIT, immune checkpoint inhibitors (ICI) or chemotherapy alone. Overall survival (OS), objective response rate (ORR), event-free survival (EFS), and toxicities were assessed. Among 60 patients, 33 received CIT upon disease progression on PD-1 blockade. At a median follow-up of 3.9 years, the CIT group had a median OS of 3.5 years [95% confidence interval (CI) 1.7–NR] vs. 1.8 years (95% CI 0.9–2; P = 0.002) for those who received subsequent ICI (n = 9) or chemotherapy alone (n = 18), with ORR of 59% vs. 15% (P = 0.0003), respectively. The median EFS was 7.6 months (95% CI 6–10) following CIT vs. 3.4 months (95% CI 2.8–4.1; P = 0.0005) following ICI or chemotherapy alone. Therapy-responsive CX3CR1+CD8+ T-cells showed dynamic increase with successful CIT. CIT showed favorable clinical outcomes and acceptable safety profile in PD-1 blockade-resistant patients. CX3CR1+CD8+ therapy-responsive T-cells can be potentially used for monitoring disease response to CIT.

AbstractObjectivePrevious studies have reported a close relationship between malignant mesothelioma (MM) and the immune matricial microenvironment (IMM). One of the major problems in these studies is the lack of adequate adjustment for potential confounders. Therefore, the aim of this study was to identify and quantify risk factors such as IMM and various tumor characteristics and their association with the subtype of MM and survival.MethodsWe examined IMM and other tumor markers in tumor tissues from 82 patients with MM. These markers were evaluated by histochemistry, immunohistochemistry, immunofluorescence, and morphometry. Logistic regression analysis, cluster analysis, and Cox regression analysis were performed.ResultsHierarchical cluster analysis revealed two clusters of MM that were independent of clinicopathologic features. The high‐risk cluster included MM with high tumor cellularity, high type V collagen (Col V) fiber density, and low CD8+ T lymphocyte density in the IMM. Our results showed that the risk of death was increased for patients with MM with high tumor cellularity (OR = 1.63, 95% CI = 1.29‐2.89, P = .02), overexpression of Col V (OR = 2.60, 95% CI = 0.98‐6.84, P = .04), and decreased CD8 T lymphocytes (OR = 1.001, 95% CI = 0.995‐1.007, P = .008). The hazard ratio for the high‐risk cluster was 2.19 (95% CI = 0.54‐3.03, P < .01) for mortality from MM at 40 months.ConclusionMorphometric analysis of Col V, CD8+ T lymphocytes, and tumor cellularity can be used to identify patients with high risk of death from MM.

Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

Abstract Background: Current dogma for the management of patients with PV dictates controlling erythrocytosis (to goal hematocrit levels of &lt;45% (males) or &lt;42%(females)) to decrease risks of thrombohemorrhagic complications. Control is achieved by either phlebotomy (through induction of iatrogenic iron deficiency), and/or direct myelosuppression (through hydroxyurea, interferon-alpha, or anagrelide). Although phlebotomy is clinically considered a very benign therapy, we hypothesize that PV associated fatigue is exacerbated by iron deficiency induced fatigue (Qual Life Res2000;9:5(491–7)), and evaluated the impact of therapeutic control of erythrocytosis on PV patients. Methods: A detailed analysis of patients with PV whom responded to an international web based survey of MPD patients which registered responses regarding diagnosis, disease course, current medications, current blood counts, frequency of phlebotomy, constitutional symptoms, and fatigue (FACT-An and Brief Fatigue Inventory). Results: A total of 405 self reported PV patients (median age 56; 48% female) from a wide geographic international distribution responded. Individuals were a median of 4 years from their initial diagnosis of PV (range 0–36). Prior PV associated complications were reported as thrombotic (n=98; 24%), hemorrhagic (n=101; 25%), or both events (n=37; 9%). When these latter values were combined with age (i.e. &gt;60 years) 61% of patients (n=246) would be considered high risk. Therapy for their PV was reported by 96% (n=388) patients, with 89% (361) having been phlebotomized, 72% (n = 291) received aspirin, 64% (n = 261) having received 1 or more myelosuppressive agent (hydroxyurea 53% (n = 216), anagrelide 22% (n = 88), interferon-alpha 16% (n = 63)). Amongst patients whom were phlebotomized over the past year (43%; n =174: median 4 units (range 1–18)), 53% (n = 92) received concurrent myelosuppressive therapy. Amongst patients whom originally, but no longer required phlebotomy 35% (n = 142), 94% (n = 134) were receiving myelosuppressive treatments. QOL assessments indicated fatigue as measured by both instruments is clearly increased across the PV respondents compared to published controls for those instruments (p&lt;0.001). Additionally, although the burden of fatigue was not significantly higher in “high-risk” PV, fatigue levels were higher amongst those with prior thrombo-hemorrhagic events (p=0.03, or both types of events p&lt;0.01). In regards to the impact of PV therapy upon fatigue, the burden of this symptom was not significantly diminished for those individuals on phlebotomy alone compared to those on cytoreductive therapy. Neither did fatigue levels correlate with the frequency or intensity of phlebotomy. Additionally, although fatigue burden was high (compared to controls) amongst patients on cytoreductive therapy, no agent had a clear advantage in alleviating (or disadvantage in exacerbating) fatigue. Conclusions: Fatigue amongst patients with PV is significantly increased compared to controls, and no therapeutic option seems to have a significant advantage with regards to fatigue. Given the multifactorial and subjective nature of fatigue it is impossible to separate the individual contributions of disease activity and therapy to the burden of fatigue in these patients. Hopefully, targeted therapy against the molecular origins of myeloproliferation in these patients will lead to better improvements in fatigue than current options offer.

Abstract Systemic capillary leak syndrome (SCLS) is a vascular disorder characterized by intermittent episodes of hypotension and edema from increased vascular permeability. Patients present with resultant dramatic shifts in plasma volume from intravascular to extravascular spaces. Diagnosis requires observation of severe hemoconcentration and hypoalbuminemia during acute attacks. Typically, laboratory evaluation of hematocrit and albumin is normal when patients are not symptomatic. Concomitantly, and of unknown significance, a monoclonal protein is also frequently discovered. We present the case of a patient whose increased hematocrit suggested polycythemia vera, but whose total clinical picture of hypotension, hemoconcentration and hypoalbuminemia confirmed the diagnosis of SCLS. A 54-year old gentleman was referred for evaluation of polycythemia vera that was diagnosed after a series of dramatic hospitalizations for near-syncope. The patient had no chronic illnesses, negative family history for hematologic abnormalities, and was otherwise in his usual state of good health when a complaint of sudden lightheadedness and pre-syncope led to an emergency room evaluation. There he was found to be severely hypotensive and was resuscitated with intravenous fluids. Initial laboratory evaluation showed a hematocrit of 60%. Further workup revealed an increased red cell mass. For the presumptive diagnosis of polycythemia vera, the patient was phlebotomized once and, interestingly, did not require any further phlebotomy for almost three years. During this interim, he remained relatively asymptomatic with only occasional bouts of lightheadedness that would abort with increased fluid hydration. Phlebotomy was again used when the patient presented with near-syncope, hypotension, and vomiting accompanied by significant extremity swelling. The hematocrit was found to be greater than 80%. The patient recovered with aggressive fluid resuscitation and was discharged on a low-dose aspirin with the continued empiric diagnosis of polycythemia vera. During that year, the patient recovered from four other similar episodes that resolved after fluid resuscitation and where phlebotomy was used. The most severe episode involved a protracted ICU stay for severe hypotension complicated by severe extremity edema and resultant compartment syndrome and ischemic muscle necrosis. With the concern of adrenocortical dysfunction leading to these hypotensive episodes, the patient was started on low dose daily steroids. While on this, the patient reported less frequency and severity of his almost-daily symptoms of lightheadedness and edema. In fact, attempts at tapering the steroid dose down resulted in a return of the minor symptoms and with continued steroids, no further hospitalizations were needed. During our evaluation, we confirmed a normal hematocrit and albumin while asymptomatic and the presence of a monoclonal protein. This case represents a common clinical history of patients who are ultimately diagnosed with SCLS. Often, the significance of the observed hypotension in concert with laboratory evidence of hemocentration and hypoalbuminemia is not initially appreciated. Although current attack prophylaxis regimens for SCLS use terbutaline and theophylline, steroids had historically shown occasional benefit in some patients. SCLS still carries a significant mortality risk and prompt recognition of this syndrome and initiation of an appropriate prophylaxis regimen is crucial.

Abstract BACKGROUND. Several studies have recently reported on the occurrence of a JAK2 V617F mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation is currently under study. Similarly, there is limited information regarding the correlation of JAK2 V617F mutational status and neutrophil PRV-1 transcript level in PV, secondary polycythemia (SP) and other myeloproliferative disorders (MPD). METHODS. In a single institutional study, mutation screening for JAK2 V617F was performed in DNA derived from archived blood granulocytes from 63 consecutive patients with PV in whom current diagnostic criteria were strictly applied and diagnosis confirmed by bone marrow histology. Concomitant quantitative analysis of neutrophil PRV-1 expression was performed in 28 of the 63 patients and the results of both JAK2 V617F and PRV-1 analysis in these 28 patients were compared with those from another 22 patients with essential thrombocythemia (ET), 10 with myelofibrosis with myeloid metaplasia (MMM), 19 with SP, and 11 healthy volunteers. RESULTS. The 63 patients with PV were followed for a median of 33 months (range 3–324) from the time of initial diagnosis. During this period, 3 patients have died including 2 from acute myeloid leukemia (AML). Disease transformation into either AML or MMM has occurred in 2 and 4 patients, respectively. The median time from diagnosis to the time of mutation analysis was 12 months (range 0–306). JAK2 V617F was detected in 58 of the 63 patients with PV (92%; homozygous in 21%). The clinical phenotype of the 5 patients with wild-type allele was otherwise typical for the disease. A statistical comparison between JAK2 V617F heterozygotes (n=45) and homozygotes (n=13) in PV did not reveal significant associations in regards to age, gender, leukocyte or platelet count at diagnosis, disease duration, or the incidences of thrombosis or bleeding. However, JAK2 V617F homozygotes, compared to their heterozygote counterparts, displayed significantly higher hemoglobin level at diagnosis (p=0.001), increased incidence of pruritus (69% vs. 38%; p=0.04), and a higher rate of fibrotic transformation (23% vs. 2%; p=0.009). The overall (homozygous) JAK2 V617F mutational frequencies in the other study patients with ET, MMM, SP, and healthy controls were 55% (0%), 30% (0%), 0%, and 0%, respectively. The corresponding figures for increased PRV-1 expression in these patients were 18%, 20%, 21%, and 9% as compared to 89% in PV. In patients with either ET or MMM, the likelihood of detecting JAK2 V617F was significantly higher in the presence of an increased PRV-1 expression (83% vs. 38%; p=0.05). Similarly, in patients with PV, homozygous as compared to heterozygous JAK2 V617F correlated with higher levels of PRV-1 expression (p=0.07). CONCLUSIONS. The current clinical study demonstrates a mutant allele dose effect on erythrocytosis, PV-characteristic clinical features, and granulocyte PRV-1 expression in PV. Furthermore, compared to the PRV-1 assay, mutation screening for JAK2 V617F displayed greater specificity in distinguishing PV from SP.

Abstract Background: It is widely accepted that an elevated serum endogenous erythropoietin (EPO) level in a patient presenting with erythrocytosis and a genuinely increased red cell mass makes a diagnosis of polycythemia vera (PV) extremely unlikely (Mossuz et al Haematologica2004:1194; Tefferi and Gilliland Mayo Clin Proc2005:947.) However, in the absence of a definitive molecular marker for PV, there is often uncertainty, especially when PV-associated clinical features are present. Here we describe 4 patients presenting with Budd-Chiari syndrome (BCS) and erythrocytosis who had EPO levels well above the normal reference range (Levy et al Hepatology1985:858), yet all had the newly described JAK2 V617F point mutation in myeloid cells, confirming PV. Methods and Results: A 30-year-old man presented in March 2005 with ascites, mild splenomegaly, abnormal liver tests, and erythrocytosis (hemoglobin (Hb) 18.6 g/dL) with a normal platelet count (187 x 10(9)/L). BCS was diagnosed by Doppler ultrasonography, transjugular venogram, and liver biopsy. While bone marrow examination showed hypercellularity and megakaryocyte clustering consistent with chronic myeloproliferative disorder (CMPD), his EPO level was elevated to 32 U/L (normal 4–16 U/L), suggesting secondary erythrocytosis. Arterial oxygen saturation, Hb oxygen-dissociation curves (P50), molecular studies of the globin loci, Hb chromatography, and CT scans of the body were all normal. Granulocyte DNA demonstrated the JAK2 V617F mutation (heterozygous/mixed clonality), absent in buccal cells, confirming PV. Karyotype was normal and BCR/ABL was not present. The patient was treated with phlebotomy, warfarin, and hydroxyurea. One month later, his EPO level was markedly reduced at 13 U/L. We hypothesized that since hepatocytes express low levels of EPO, a remnant of fetal erythropoiesis, acute necrosis from BCS could lead to transient EPO surge even in the presence of chronic EPO suppression from PV. We then reviewed clinical data from all 33 patients at our institution since 1995 with BCS that was ultimately believed to be associated with PV. We identified 13 such patients in whom endogenous EPO levels were measured. Most had a low EPO level at the time of diagnosis (range of &lt;1.5 to 9 U/L), but 3 of these patients were found to have an elevated EPO level. DNA was extracted from archival samples from these 3 patients; JAK2 V617F mutation was detected in all 3. Clinical presentations were as follows: Patient 1: 21-year-old woman with BCS and pulmonary embolus, Hb 15.9 mg/dL, EPO 28 U/L. Bone marrow biopsy was consistent with PV. Subsequent EPO level was 19U/L in the setting of progressive liver failure. Patient 2: 48-year-old woman with known PV receiving intermittent phlebotomy presented with BCS, Hb 17.2 mg/dL, EPO 25 U/L. Marrow was consistent with CMPD. Patient 3: 33-year-old woman presented with BCS, Hb 18.8 mg/dL, EPO 53 U/L. Bone marrow biopsy showed early CMPD. Conclusion: Elevated EPO levels do not exclude the diagnosis of PV, especially in the presence of BCS with hepatic necrosis. These cases highlight the continuing challenges in accurate PV and CMPD diagnosis and emphasize the importance of complementing clinical assessment with molecular genetic testing, including JAK2 mutation analysis.

Abstract Background: Leukocytosis has recently been implicated as an adverse prognostic feature for thrombosis in both ET and PV. Such an association would be therapeutically most relevant in the context of “low-risk” disease. In the current study, we sought to clarify the relationship between leukocytosis at diagnosis and the subsequent occurrence of either arterial or venous thrombosis, in “low-risk” patients with ET or PV. Methods: Data was abstracted from the medical records of a consecutive cohort of patients with WHO-defined ET or PV seen at the Mayo Clinic. Low-risk disease was defined by the absence of both thrombosis history and age 3 60 years. Cox proportional hazards model was utilized to determine the impact of clinical and laboratory variables on thrombosis-free survival (TFS). Arterial- or venous-specific TFS curves were constructed by Kaplan-Meier method. Results: i) Patient characteristics and outcome A total of 407 “low-risk” patients were studied; 153 had PV (median age 48 years; females 43%) and 254 ET (median age 42 years; females 71%). A total of 46 thrombotic events (22 arterial and 24 venous) were recorded in 41 (27%) patients with PV during a median follow up of 130 months (range 2–562 months). The corresponding figures in ET were 54 total thrombotic events (41 arterial and 14 venous) in 47 (19%) patients at a median follow up of 104 months (range 0.25–424 months). Cytoreductive therapy was avoided in the presence of &lt; 1000 x 109/L platelet count but, at the discretion of the treating physician, some patients with higher platelet counts received prophylactic cytoreductive therapy. ii) Correlation between leukocytosis and thrombosis A leukocyte count of 3 15 x 109/L at diagnosis was documented in 42 (27%) patients with PV and 21 (8%) patients with ET; 102 patients (40%) with ET had &gt; 9.4 x 109/L leukocyte count. Leukocyte count considered as either a continuous or categorical variable (using cutoff levels of 15 x 109/L for PV and either 15 x 109/L or 9.4 x 109/L for ET) was not significantly associated with either arterial or venous thrombosis (Figure 1). iii) Correlation between other risk factors and thrombosis In univariate analysis, presence of the JAK2V617F was significantly associated with arterial thrombosis in ET (p=0.049) but significance was lost during multivariable analysis that included age as a covariate. Only advanced age was found to be significantly associated with arterial thrombosis in PV (p=0.04) and higher hemoglobin level with venous thrombosis in ET (p&lt;0.0001). Conclusion: The current study does not identify leukocyte count at diagnosis as a marker of increased thrombosis risk in low-risk patients with either ET or PV. Instead, the study found an association between arterial thrombosis and advanced age in PV and venous thrombosis and higher hemoglobin level in ET. Figure Figure

Abstract Background: Immunomodulatory therapy has been shown to be of benefit for the improvement of anemia, thrombocytopenia and splenomegaly in patients with myelofibrosis (MF) initially with thalidomide (Blood2000;96:4007), and further enhanced by combination therapy with corticosteroids (Blood2003;101:2534). We sought to further enhance our previously reported efficacy of single agent lenalidomide for MF patients (Blood2006;108:1158) by combination therapy with prednisone. Methods: Symptomatic patients with MF (all with baseline anemia, hemoglobin &lt;10g/dL or transfusion dependent) were enrolled in the single arm Phase II trial. Adequate neutrophils (&gt;1 x 109/L) and platelets (&gt;100 x 109/L) were required for trial entry. Lenalidomide was administered at 10 mg daily with a 3 month prednisone taper (30mg/daily, 15 mg daily, 15 mg every other day months 1,2, and 3, respectively). Patients with at least stable disease remained on single agent lenalidomide for an additional 3 months. Responses were assessed by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Response Criteria (Blood2006;108:1498). Results: Patients 28 patients were enrolled in the first step of the trial, and a total of 48 patients were enrolled (3 were ineligible because of proximity of prior therapy with 43 deemed evaluable). The enrolled eligible patients (56 % males) had a median age of 64 (range 18–83). At baseline, 52% were red cell transfusion dependent, and the median hemoglobin amongst those non transfusion dependent patients was 8.8 g/dL (range 5.9–12.4). By entry criteria neutrophils (median 5.1 x 109/L (range 1.0–79.4)) and platelets (median 234 x 109/L (range 40–1253)) were adequate. Therapy and Toxicity: A median of 6 cycles of therapy was administered, 10 patients received 3 months, and 25 patients the full 6 months of therapy. Premature discontinuation of therapy occurred in 19 patients; progressive disease (3), toxicity (7), patient withdrawal (5), death from disease (1), comorbidities (2), or seeking alternative therapy other (1). Myelosuppression was the main toxicity with 45% experiencing ≥ grade 3 hematologic toxicity (16%/2% and 23%/26%, grade 3/4 thrombocytopenia and/or neutropenia, respectively) and with 34% of patients having ≥ grade 3 non-hematologic toxicity. Less severe toxicities (&lt; grade 3) were again mainly secondary to myelosuppression (34%) or gastrointestinal (i.e. diarrhea). No significant steroid induced toxicities were observed. Response: Among 43 patients eligible for response assessment the best confirmed response observed was a partial response in 11 (26%), stable disease (54%), and progression during trial in 8 (18%), 1 was not evaluable because no medication was taken. Among the latter responses improvement in anemia was seen in 9 (21%) (IWG-MRT clinical improvement (CI)-sustained normalization of hemoglobin, &gt;2 g/dL increase, or transfusion independence for &gt;2 months), and major reductions in spleen size in 4 (9%) (IWG-MRT CI - sustained &gt;50% decrease). Serial marrow analysis was available in a subset which did not show any significant resolution of disease related fibrosis, hypercellularity or increased angiogenesis typical of MF. Conclusions: 1) Lenalidomide plus a corticosteroid taper was active in patients with MF primarily in those who suffer from anemia, but myelosuppression (particularly neutropenia is common) 2) Response rates observed with combination therapy are almost identical to our previously reported response rate seen with single agent lenalidomide (22% single agent, 21% in this trial), 3) Current results would suggest that given the myelosuppression observed, and rates of efficacy, thalidomide and prednisone would be first line for treating MF associated cytopenias with lenalidomide being considered second line (first line if a del(5q) present).