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Structural heart disease (SHD) emergencies include acute deterioration of a stable lesion or development of a new critical lesion. Structural heart disease emergencies can produce heart failure and cardiogenic shock despite preserved systolic function that may not respond to standard medical therapy and typically necessitate surgical or percutaneous intervention. Comprehensive Doppler echocardiography is the initial diagnostic modality of choice to determine the cause and severity of the underlying SHD lesion. Patients with chronic SHD lesions which deteriorate due to intercurrent illness (eg, infection or arrhythmia) may not require urgent intervention, whereas patients with an acute SHD lesion often require definitive therapy. Medical stabilization prior to definitive intervention differs substantially between stenotic lesions (aortic stenosis, mitral stenosis, left ventricular outflow tract obstruction) and regurgitant lesions (aortic regurgitation, mitral regurgitation, ventricular septal defect). Patients with regurgitant lesions typically require aggressive afterload reduction and inotropic support, whereas patients with stenotic lesions may paradoxically require β-blockade and vasoconstrictors. Emergent cardiac surgery for patients with decompensated heart failure or cardiogenic shock carries a substantial mortality risk but may be necessary for patients who are not eligible for catheter-based percutaneous SHD intervention. This review explores initial medical stabilization and subsequent definitive therapy for patients with SHD emergencies.

Abstract Background: We had previously piloted thalidomide treatment in MMM and showed an approximately 20% response in terms of both anemia and splenomegaly (Elliott et al. BJH2002;117:288). Encouraged by this experience, we undertook the current phase II study to explore the therapeutic activity of the more potent as well as less neurotoxic immunomodulatory drug, lenalidomide (CC-5013). Methods: The study group comprised a consecutive series of patients with MMM that fulfilled protocol entry criteria that included hemoglobin level ≤ 10 g/dL, platelet count ≥ 100 x 109/L, and neutrophil count ≥ 1 x 109/L. The treatment program consisted of daily oral lenalidomide (10 mg/day) for 3 consecutive 28-day cycles with a plan to continue with additional 3 cycles in case of response. Results: i. Pretreatment patient information Twenty-seven patients (median age, 66 years; range, 40–78) were accrued between March 5, 2004 and June 15, 2005. Median duration of disease prior to protocol treatment was 30 months (range, 1–245). Previous therapy was documented in all but 2 patients. Twenty patients were RBC transfusion-dependent. Baseline median (range) values for palpable spleen size, leukocyte count, platelet count, CD34 cell count, and serum lactate dehydrogenase (LDH) were 16 cm (0–31), 8.4 x 109/L (1.8–84.4), 299 x 109/L (124–831), 166.1 x 106/L (2.8–5176.4), and 778 U/L (267–1725), respectively. Cytogenetic abnormalities were detected in 13 patients (48%). JAK2 V617F mutation analysis was performed in 21 patients and revealed homozygous, heterozygous, and wild-type alleles in 3, 8, and 10 patients, respectively. ii. Adverse events Adverse events (any/grade 3 or 4) with definite, probable, or possible attributions to the drug included fatigue (52%/12%), neutropenia (40%/24%), pruritus (36%/0%), thrombocytopenia (28%/8%), anemia (16%/8%), rash (12%/8%), and respiratory distress with hypoxia (8%/8%). To date, 7 deaths have been reported, all occuring after discontinuation of protocol therapy, and none were directly linked to the drug. iii. Response The median post-treatment follow up is now 16 months (range 1–17 months). During this period, 6 patients (22%) have experienced either a major (3 patients normalized their hemoglobin level), minor (2 patients became transfusion-independent), or marginal response in anemia. The median time to response and response duration were 2 and 7 months, respectively. Two of the 3 major responders had a baseline der(1;18)(q10;q10) or del(5)(q13q33) cytogenetic abnormality, the latter one of which displayed a major cytogenetic remission. In the patient with der(1;18)(q10;q10), the hemoglobin level increased to a level of 19.1 g/dL from being transfusion-dependent at the start of lenalidomide therapy. Interestingly, the particular patient was homozygous for the JAK2 V617F mutation. Responses were also recorded for palpable splenomegaly (26%), constitutional symptoms (67%), and serum LDH level (70%). Seven patients normalized their LDH. Conclusion: Lenalidomide therapy improved anemia in at least 20% of patients with MMM. Some of the responses were spectacular and appeared to be associated with specific cytogenetic abnormalities. The documentation of a positive drug effect on LDH, constitutional symptoms, and splenomegaly in patients not showing early response in anemia suggests the possibility of an even higher response rate with a longer treatment schedule.

Abstract Background. The strongest established prognostic factors for follicular lymphoma are age and clinical factors. Biologic studies suggest a major role for the host immunologic environment in follicular lymphomagenesis, which is in part determined by host genetic background. Cytokines are key regulators of immune function and regulation, are highly polymorphic, and have been implicated in lymphoma etiology and prognosis. We evaluated the hypothesis that inherited variability in cytokine and related immune genes impact overall survival in follicular lymphoma. Methods. We genotyped 73 single nucleotide polymorphisms (SNPs) from 44 candidate cytokine and immune genes in 278 follicular lymphoma patients who participated in a population-based case-control study conducted from 1998–2000 in the Detroit, Iowa, Los Angeles and Seattle SEER (Surveillance, Epidemiology and End Results) cancer registries. Baseline clinical data and survival through early 2005 were obtained from cancer registry files. Cox proportional hazards analysis was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for the association between individual SNPs and overall survival, adjusting for age, demographic and clinical factors. We also used parallel modeling strategies to identify the best summary multi-SNP risk score to predict survival, and applied these results in a time-dependent receiver-operator characteristics (ROC) analysis. Results. The median age at diagnosis was 57 years (range, 25–74), and 59 (21%) of the patients died during follow-up, with a median follow-up of 59 months (range, 27 – 78 months) for surviving patients. In multivariate modeling, SNPs in IL8 (rs4073; HRTT=2.14, 1.26–3.63), IL2 (rs2069762; HRGT/TT=1.80, 1.06–3.05), IL12B (rs3212227; HRAA/CC=1.83, 1.06–3.06), and IL1RN (rs454078; HRAA=1.93, 1.11–3.34) were the strongest and most robust predictors of survival. A summary score of the number of deleterious genotypes from these four genes was strongly associated with survival (p=1.4 × 10−5) after accounting for demographic and clinical variables (HR=2.06 per deleterious genotype, 1.52–2.79). A combination of the four SNPs and the demographic and clinical risk scores was strongly associated with survival (p=1.8 × 10−11); the 5-year Kaplan Meier survival estimates were 96% (93%–100%), 72% (62%–83%) and 58% (48%–72%) for low, intermediate, and high risk groups respectively. In a time-dependent ROC analysis the three risk groups had an area under the curve (AUC) of 0.83 at 72 months of follow-up (95% CI 0.72–0.93). Conclusion: Host genetic variability in immune genes, particularly IL8, IL2, IL12B, and IL1RN, individually and particularly in combination, was associated with overall survival in follicular lymphoma after accounting for demographic and clinical factors. Host immunogenetics is a promising class of prognostic factors in follicular lymphoma that warrants further evaluation.

Abstract Background: While the therapeutic armamentarium for plasma cell disorders have expanded recently with introduction of thalidomide, lenalidomide and bortezomib, these diseases are still incurable and more agents are needed. We have previously demonstrated expression of CD 52 on plasma cells in MM, MGUS and AL amyloidosis. Based on this data we conducted a Phase II Study of Campath (Alemtuzumab; Monoclonal Anti-CD52 Antibody) in Primary Systemic Amyloidosis and Relapsed or Refractory Multiple Myeloma. Methods: The study was an IRB approved, Phase II protocol, with a two stage design and interim analysis at 14 patients, to assess the efficacy and toxicity of Alemtuzumab. The regimen involved a dose escalation during week one (Day I 3 mg SQ; Day II 10 mg SQ; Day III 30 mg SQ; then 30 mg SQ three times a week for a planned total of 17 additional weeks). All patients received concurrent Co-Trimoxazole, Fluconazole and Valacyclovir prophylaxis. The planned accrual was 32 patients. Results: A total of 14 patients were accrued, 8 patients with MM and 6 patients with AL. There were 8 females and 6 males in the study. The median age was 62 years (range: 50–78) years. The patients were heavily pretreated with the median number of treatments being 4. There were 5 grade 3–4 toxicities (CMV viremia (2 pts), skin rash (2 pts), and febrile neutropenia (1 pt)). Seven patients had evidence of disease progression and were removed from study. One patient completed the treatments with a mixed response. One patient had a sudden death while on study. The median duration of therapy was 6 weeks (range 3 weeks to 17 weeks). The accrual was stopped after 14 patients when the interim analysis showed a lack of anti-tumor efficacy and significant toxicity. Conclusion: This phase II study in patients with relapsed / refractory myeloma or amyloidosis demonstrated no evidence of clinical activity with use of Campath. In addition it was also associated with significant toxicity in this population. We do not recommend use of campath as a primary treatment modality in these patients. The lack of efficacy despite demonstrated expression of CD52 on clonal plasma cells once again highlights the need for combining treatments with multiple mechanisms in order to improve the response and outcome in these patients. Whether it can synergize with other therapies at lower doses without significant toxicity remains unknown.

Abstract Background: Pre-treatment cytogenetics is a known predictor of outcome in haematological malignancies. However, its value in adult ALL is generally limited to the presence of the Philadelphia (Ph) translocation; mostly due to the low incidence of other recurrent chromosomal abnormalities. Methods: Since 1993, cytogenetic data from patients enrolled on a joint MRC/ECOG trial have been collated and reviewed centrally in the UK and US. Karyotype data from patients registered before the Imatinib amendment were pooled using standard cytogenetic definitions and classification criteria. Results: A successful cytogenetic result was achieved in 938/1235 (76%) cases; while 297 (24%) failed with <20 normal metaphases analyzed. Patients were classified into the following mutually exclusive groups: t(9;22)(q34;q11) n=193(21%); t(4;11)(q21;q23) n=50(5%); other MLL translocations n=11(1%), t(8;14)(q24;q32) and variants n=14(1%); t(1;19)(q23;p13) n=23(2%); T cell receptor translocations n=35(4%); low hypodiploidy (30–39 chromosomes) /near triploidy n=23(2%); high hyperdiploidy n=83(9%); tetraploidy n=12(1%); complex karyotype (>=5 aberrations) n=48(5%); other abnormal n=255(27%); normal n=191(20%). MRC and ECOG patients showed similar cytogenetic distributions, except for t(9;22), which was significantly more prevalent in the ECOG cohort (27% v 18%, p<0.001). However, the incidence of t(9;22) increased with age and ECOG patients were significantly older. Overall, the 5 year event free survival (EFS) was 32% (95% CI 30%–35%) with a median follow-up time of 5.1 years and did not differ between the two cohorts. The EFS of t(9;22) patients [15% (11%–21%)] was significantly inferior compared with all other cases [36% (32%–39%)] (p<0.001) and was independent of age and white cell count (WCC). Univariate logrank analyses identified t(4;11) and high hyperdiploidy as indicators of poor and good prognosis, respectively, compared with other Ph negative cases, but neither was independent of age and WCC. Three subgroups were shown to have a significantly worse EFS compared to other Ph negative cases by logrank analyses after adjusting for age and WCC: t(8;14) 14% (2%–37%) v 36% (32%–40%) (p=0.01); low hypodiploidy 22% (8%–40%) v 36% (32%–40%) (p=0.02); complex karyotype 21% (10%–33%) v 32% (29%–35%) (p=0.005). Neither of the latter two subgroups were associated with other poor risk features such as age, WCC or failure to achieve a remission within 4 weeks. Conclusions: This is the largest cytogenetic dataset of adult ALL reported to date and demonstrates the importance of combining cohorts to increase the number of cases available for analysis. The observation that low hypodiploidy and, for the first time, karyotype complexity confer a poor risk, demonstrates that cytogenetic subgroups other than the Ph translocation can and should be used to risk stratify adults with ALL to alternative treatments.

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: Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. For selected patients high dose chemotherapy with peripheral blood stem cell support is effective, but even in those patients, only 50% derive organ responses. Other patients are too sick to undergo that therapy. Thalidomide has limited utility in this disease, largely because of its toxicity profile in patients with AL. Lenalidomide, Celgene’s lead clinical compound in a new group of drugs called IMiDs®, is highly active in patients with multiple myeloma, especially in conjunction with dexamethasone. We sought to determine the toxicity and efficacy of lenalidomide in patients with AL. Methods: Patients with symptomatic AL who had a measurable plasma cell disorder (defined as serum M-spike ≥ g/dL urine M-spike >200 mg/24 hours; or involved immunoglobulin free light chain (FLC) ≥10 mg/dL and an abnormal FLC ratio) and adequate organ reserve defined as a creatinine ≤3 mg/dL, absolute neutrophil count ≥1000, platelet count ≥75000, and a hemoglobin ≥8 g/dL were eligible. Patients were started on lenalidomide 25 mg/day for 21 days followed by a 7 day rest (1 cycle). Dose modifications were made based on toxicity. If there was evidence of progression before 3 months or no evidence of hematologic response after 3 cycles, dexamethasone 40 mg p.o. days 1–4 and 15–18 was added. Results: Twenty-three patients were enrolled between 10/28/04 and 4/7/05; 14 were previously treated. Patient characteristics are shown in Table. Organ involvement was as follows: cardiac (61%); renal (70%), hepatic (22%); nerve (13%). Nine patients withdrew from study before completing 3 months of therapy. The reasons were: cancel (1); death (4); adverse events (2); and progression (2). At the time of our preliminary analysis in July 2005, an additional 3 patients have withdrawn from study: death (1) and patient refusal (2). Of the 5 patients who died, 4 had severe cardiac involvement and at least 3 organs involved by amyloid. The median follow-up for the eleven patients remaining on study is 6.2 months. Of the 12 patients who have crossed the 3 month treatment landmark, there are 7 hematologic partial responses (4 confirmed and 3 unconfirmed), two renal responses and one liver response. Of these same 12 patients, all but one has had dexamethasone added to their treatment program. The most common grade 3–4 adverse advents at least possibly attributable to lenalidomide were neutropenia (43%), thrombocytopenia (26%), rash (17%), dyspnea (9%), fatigue (9%), and edema (4%). Expansion of the trial is planned to accrue an additional 10 evaluable patients. Conclusions: Early results suggest that lenalidomide ± dexamethasone has activity in patients with primary systemic amyloidosis. Supported in part by the Caliguiri Fund for Amyloidosis Research, Robert A. Kyle Hematologic Malignancies Program, and Celgene. Patient Characteristics Median Range Age 64 44–88 Major Organs 2 0–3 Involved FLC, mg/dl 23 4.1–278 Serum alb, g/dl 2.8 1.2–3.7 Urine protein, g/24 hrs 3.7 0.02–14.3 Creatinine, mg/dl 1.3 0.7–2.6 Alkaline phos IU/l (nml <115) 99 57–1729 NY Heart Class 1 1–3 Troponin T, mcg/l 0.03 0.01–0.55 NT-proBNP, ng/l 1419 109–42844 LV Septum, mm 13 9–24 LV EF, % 63 22–72

Abstract Background: One of the utilities of molecular markers in hematological malignancies is their potential to predict response to drug therapy. Accordingly, we inquired about the effect of both cytogenetic profile and JAK2V617F mutational status on drug therapy response in myelofibrosis with myeloid metaplasia (MMM). Methods: Mutation analysis for JAK2V617 was performed in DNA derived from peripheral blood mononuclear cells, granulocytes, or both. Genomic DNA was amplified by PCR and fluorescent dye chemistry sequencing was performed using the same primers used for amplification (Levin et al. Cancer Cell2005;7:387). Abnormal cytogenetic findings were considered to be either favorable (sole 13q- or 20q- abnormalities) or unfavorable (other abnormalities) (Tefferi et al. BJH2001;113:763). Results: i. Patients and treatment: A total of 69 patients with MMM (median age 62 years, range 38–75; 47 males) received the following drugs as first-line therapy for either anemia or symptomatic splenomegaly; erythropoietin (Epo) alone or in combination with hydroxyurea (n=25), hydroxyurea alone (HU; n=17), interferon alpha (IFN; n=11), combination of thalidomide and prednisone (ThalPred; n=7), androgen preparations (Andro; n=5), and etanercept (n=4). ii. Results of cytogenetic studies and JAK2 mutation screening: Cytogenetic findings were abnormal in 35 patients (51%); favorable in 9 and unfavorable in 26. JAK2V617 mutation analysis revealed wild-type allele in 31 patients (45%) and either heterozygous (n=31) or homozygous (n=7) mutation in the remaining 38 patients (55%). iii. Correlation of response to cytogenetic/molecular markers: Overall, 17 patients (25%) achieved either a major (n=8) or minor (n=9) response in anemia from treatment with one of the aforementioned drugs. Regardless of either JAK2V617 mutational status or cytogenetic profile, treatment-induced responses in anemia were poor for IFN (0%) and HU (12%). In contrast, the best anemia responses were documented for ThalPred (57%), Andro (40%), and Epo-based therapy (32%). Among the 25 patients that received Epo-based therapy, all 3 patients with favorable cytogenetic abnormalities achieved major responses in anemia whereas such responses were seen in none of the 9 patients with unfavorable cytogenetic abnormalities and only 1 of 13 patients with normal cytogenetics (p=0.004). Furthermore, 3 of the 4 major responders were heterozygous for JAK2V617 and one carried the wild-type allele. In contrast, none of the 3 JAK2V617 homozygotes showed any type of response but all 3 also displayed unfavorable cytogenetics. None of the 7 ThalPred-treated patients carried favorable cytogenetics and yet 3 achieved major responses including one with unfavorable cytogenetics. JAK2V617 mutational status was heterozygous in 1 and wild-type in the other two. There were no major responses among the 5 Andro-treated patients despite the presence of favorable cytogenetic abnormalities in 2 patients. In order to investigate the relationship between cytogenetic profile and JAK2V617 mutational status further, we referred to an expanded database of 116 patients and found the incidence of unfavorable cytogenetics to be higher in JAK2V617 homozygotes compared to non-homozygotes (57% vs. 31%; p=0.16) Conclusion: The current study suggests clustering of favorable cytogenetic abnormalities in MMM with anemia response to Epo therapy and unfavorable cytogenetic abnormalities with homozygosity for JAK2V617 mutation.

Abstract BACKGROUND: Disease manifestations in myelofibrosis with myeloid metaplasia (MMM) that require therapy include anemia, thrombocytopenia, hepatosplenomegaly, and constitutional symptoms. We have previously reported on the therapeutic value of low-dose thalidomide in combination with prednisone for the treatment of both anemia and thrombocytopenia in MMM (Blood2003;101:2534), and of etanercept (tumor necrosis factor-alpha antagonist) for alleviation of constitutional symptoms (Blood2002;99(6):2252). In the current study, we investigated the value of combining all three drugs (PET). METHODS: Study eligibility criteria included a histologically confirmed diagnosis of MMM and either severe anemia (hemoglobin < 10 g/dL) or symptomatic splenomegaly. Protocol treatment was initiated with 50 mg of oral thalidomide (THAL) daily, etanercept (ETAN) 25 mg subcutaneously twice-a-week, and a three month prednisone taper starting at 0.5 mg/kg/day for the first month followed by a 50% reduction for the second months and a further 50% reduction for the third and final month of treatment with prednisone. Patients with a demonstrable clinical response after three months were able to remain on thalidomide and etanercept. RESULTS: 15 patients were enrolled to the trial (median age 66 years, range, 54–77; 14 males). Twelve patients (80%) completed the planned three cycles (i.e. 3 months) of treatment (progression (n=2) and patient choice (n=1) accounted for the withdrawals), nine (60%) patients with evidence of response continued on an additional three months of THAL/ETAN alone (of which 3 progressed prior to study completion). At enrollment, 11 patients (73%) were anemic (7 (47%) were red cell transfusion dependent), 7 (47%) were at least moderately thrombocytopenic (platelet count < 100 x 109//L), and 6 had severe constitutional symptoms (night sweats or disease related fever). Anemia response were seen in 6 (of the 11 eligible; 54%) patients (2 in the non-transfusion dependent (sustained increases of 1.5 and 4.9 g/dL hemoglobin); 4 in transfusion dependent (1 transfusion independent, 3 >50% decrease in transfusion requirements)). All thrombocytopenic patients experienced an increase in platelet counts (median 55% increase (range(10–229) with 2 returning to the normal range (>150 x 109/L)). A greater than 50% decrease in organomegaly was documented in 3 patients with splenomegaly (25% of eligible), and 1 patient with hepatomegaly (25%). Constitutional symptoms resolved, or signifcantly improved in all afflicted. Therapy overall was well tolerated with the majority of toxicities being transient. Neuropathy (grade 1; n=3; grade 2; n=1) and hyperglycemia (grade 2; n=1) were minimal. The only greater or equal to grade 3 toxicities were (grade 3: elevated bilirubin, infection, and blurred vision; grade 4: anemia). Follow-up bone marrow examination, when available, did not show post-treatment histological changes. CONCLUSIONS: This phase II study of combination therapy with thalidomide-prednisone-etanercept in patients with MMM confirms the previously recognized value of etanercept in alleviating constitutional symptoms. However, the PET regimen does not appear to be superior to thalidomide-prednisone combination in terms of therapeutic value for anemia, thrombocytopenia, or splenomegaly.

Abstract Background: Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, has been shown to be highly active in patients with multiple myeloma. Methods: We studied the toxicity and efficacy of lenalidomide in patients with symptomatic AL. Patients received single agent lenalidomide. If progression by 3 months or no evidence of hematologic response after 3 cycles, dexamethasone was added. Originally, twenty-three patients (Cohort 1) were enrolled according to study design. Because of a significant early drop out rate and notable activity of the regimen, the trial was modified to include an additional 15 patients (Cohort 2). Baseline characteristics and adverse events are available for all enrolled patients, but at the time of this writing, response data are available for Cohort 1 patients due to short follow-up of Cohort 2, but will be updated by the time of the meeting. Results: Median age was 64 years, with 69% male. Twenty-three were previously treated. Organ involvement was cardiac (67%), renal (64%), hepatic (17%), nerve (17%). Thirty-three, twenty-two, and forty-four percent of patients were cardiac biomarker stage 1, 2, and, 3 respectively. Of the 37 patients, one was a cancel, and 6 have not yet made it through 3 months of protocol treatment and event monitoring. The respective median follow-ups for Cohorts 1 and 2 are 17 and 3.4 months. Of the remaining, 30 patients, within the first 3 cycles of therapy fifteen patients discontinued treatment: 7 early deaths and 8 adverse events or other causes. Three additional patients died 0.5 to 2 months after stopping treatment. The best predictor for early withdrawal and/or death was baseline NT-proBNP and cardiac biomarker staging system (cut-offs for serum troponin T <0.035 ng/ml and NT-proBNP <332 pg/ml--Stage I neither above cut-off; Stage III, both above cut-off; and Stage II, one above cut-off). Figure1 Figure1. Figure 2 Figure 2. Of the twenty 22 patients assessed for response ten patients responded to treatment for an overall response rate of 45%, including 23% organ responders. Among the patients with organ responses, there were four renal responses, two cardiac responses and two liver responses. All but one of the responders had dexamethasone added to their treatment program. The most common grade 3−4 adverse events at least possibly attributable to lenalidomide were neutropenia (38%), thrombocytopenia (21%), fatigue (15%), and rash (12%). Conclusions: Lenalidomide and dexamethasone has significant activity in patients with AL with an overall response rate of 45%. Baseline NT−proBNP may be an effective eligibility screening strategy for subsequent trials.