Analysis of RNA yield in extracellular vesicles isolated by membrane affinity column and differential ultracentrifugation.

Extracellular vesicles (EV) have attracted much attention as potential biomarkers due to their protein, RNA and other nucleic acid content. The most common method used for EV isolation is differential ultracentrifugation (DU), however given the DU technical difficulties, other more practical methods have surged, such as membrane-affinity column commercial kits. Here, we assessed one commercial kit in terms of EV recovery and EV-derived RNA yield and compared it with a DU protocol. Our data shows that the commercial kit preparation results in a lower count of EV-like structures and a reduced expression of EV markers when compared to DU samples. Thus, apparently suggesting that the commercial kit had a lower EV yield. However, these findings did not reflect on RNA yield, which was greater with the commercial kit, even after an enzymatic treatment with proteinase K and RNAse A. We conclude that the kit has a higher EV-derived RNA yield in comparison to our DU protocol, suggesting that it may be the method of choice for RNA sequencing purposes.

Impact of Additional Cytogenetic Abnormalities on the Clinical Behavior of Patients With Chronic Myeloid Leukemia: Report on a Latin American Population.

INTRODUCTION: Additional cytogenetic abnormalities (ACA) in patients with chronic myeloid leukemia (CML) are related to an increased risk of treatment failure, leukemic progression, and decreased survival. Currently, there are scarce data available for the Latin American population. The aim of this study was to outline the impact of ACA emergence in Mexican patients with CML. METHODS: We retrospectively analyzed clinical data from adult patients with CML treated with upfront imatinib between January 2001 and December 2016. Two groups were defined for comparison according to the presence or absence of ACA. RESULTS: Ninety-seven patients were included. ACAs were found in 30 patients, 20% at diagnosis and 80% during follow-up. In 90% of the patients, ACA emergence was detected in the CML-chronic phase. Regarding clinical outcomes, the complete cytogenetic response rate (16.5% vs. 59.8%; P < .001), progression-free survival (PFS) at 10 years (76% vs. 95%; P = .009), and failure-free survival (FFS) at 10 years (16% vs. 73%; P < .001) were significantly inferior in the ACA group. Multivariate analysis confirmed that ACA emergence was a deleterious independent prognostic factor for PFS (hazard ratio [HR] 8.9; 95% confidence interval [CI] 1.35-58.4; P = .023) and FFS (HR 3.7; 95% CI 1.54-8.58; P = .003). CONCLUSIONS: This study confirms previously reported data regarding the adverse impact of ACA over clinical outcomes in a Latin American population.

A pilot study of an accelerometer-equipped smartphone to monitor older adults with cancer receiving chemotherapy in Mexico.

OBJECTIVES: Older adults with cancer in developing countries face challenges accessing healthcare due to a lack of personnel and infrastructure. A decline in physical activity (defined as a decrease in the number of daily steps) may be a novel method for the timely detection of toxicity in older adults receiving chemotherapy in resource-constrained settings. MATERIALS AND METHODS: In this feasibility study, patients aged ≥65years starting first-line chemotherapy for solid tumors were given a smartphone with a pedometer application. Daily steps were monitored daily for one cycle. If a ≥15% decrease from baseline was identified, the patient was called and the presence of toxicity assessed. The intervention would be feasible if ≥75% of the subjects recorded steps for ≥75% of the planned chemotherapy days. RESULTS: Forty patients (median age 73; 57% [N=23] female) were included. Seventy percent (N=28) had stage III-IV disease with 45% (N=18) gastrointestinal, 23% (N=9) breast, and 32% (N=13) other malignancies. Mean pre-treatment daily steps was 3111 (Standard Deviation [SD] 1731), and median follow-up was 21days (range 2-28). Despite having limited exposure to mobile technology, most (93%) patients used the smartphone appropriately, and 85% found it easy to use. Sixty percent of patients (N=24) had toxicities managed over the phone, 27.5% (N=10) were sent for urgent medical attention and 15% (N=6) were hospitalized. CONCLUSION: Using smartphones to monitor older adults with cancer receiving chemotherapy in a resource-constrained setting is feasible and acceptable. A decrease in the number of daily steps was common and helped to identify chemotherapy toxicity.

Importance of CD117 in the Assignation of a Myeloid Lineage in Acute Leukemias.

The correct classification of acute leukemias (AL) is an essential part in the evaluation of any patient with this disease. Historically, CD117 has been an important asset in the diagnosis of patients with mixed-phenotype acute leukemia (MPAL). In an attempt to simplify the diagnosis of MPAL with fewer and more lineage specific markers, the World Health Organization (WHO) proposed in 2008 a new criteria for the diagnosis of this type of AL, which excluded CD117 from the myeloid markers that are utilized to diagnose MPAL. In order to assess whether CD117 is necessary in the diagnosis of MPAL, we evaluated the sensitivity and specificity of CD117 for acute myeloid leukemia (AML) in 331 patients with AL. The calculated sensitivity of CD117 for AML was 85.88% (103/120), while the specificity was 83.9% (177/211). Besides myeloperoxidase (MPO), which was used as the gold standard in differentiating AML from other type of ALs, the most specific markers for AML in our study were CD14 and CD64 (99.5 and 95.6%). Although the specificity of CD117 in this study is not as high as CD14 and CD64, markers concomitantly used in this this study and in the WHO classification, based on the results of other researches (i.e. the specificity of CD117 for AML was 100% in one study) and due to the fact that its specificity for AML in this study is relatively high, we recommend the use CD117 in assigning a myeloid lineage in MPAL.

Survival and treatment response in adults with acute promyelocytic leukemia treated with a modified International Consortium on Acute Promyelocytic Leukemia protocol

ABSTRACT Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries. Herein are presented the results from the first patient cohort treated in a single developing country hospital employing a slightly modified version of the International Consortium protocol in a real life setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8% had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission rate was 94.4% after a median of 42 days. Both relapse rates and death rates were one patient (5.5%) each. No deaths were observed during consolidation. After a median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and safety of the International Consortium on Acute Promyelocytic Leukemia protocol has been reproduced in acute promyelocytic leukemia patients from a developing country.

Survival and treatment response in adults with acute promyelocytic leukemia treated with a modified International Consortium on Acute Promyelocytic Leukemia protocol.

Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries. Herein are presented the results from the first patient cohort treated in a single developing country hospital employing a slightly modified version of the International Consortium protocol in a real life setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8% had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission rate was 94.4% after a median of 42 days. Both relapse rates and death rates were one patient (5.5%) each. No deaths were observed during consolidation. After a median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and safety of the International Consortium on Acute Promyelocytic Leukemia protocol has been reproduced in acute promyelocytic leukemia patients from a developing country.

Fluorescent In Situ Hybridization Monitoring and Effect of Detected Early Responses in the Outcome of Patients With Chronic Phase Chronic Myeloid Leukemia: A Report From a Latin American Country.

INTRODUCTION: The cytogenetic hallmark of chronic myeloid leukemia (CML) is the Philadelphia chromosome. Monitoring the response in patients receiving therapy is a standard of care. The present study was conducted to assess the monitoring adherence and reliableness of fluorescent in situ hybridization (FISH) as a monitoring tool and the effect of a complete cytogenetic response (CCyR) assessed by FISH on the prognosis of patients in a chronic phase (CP)-CML cohort. MATERIALS AND METHODS: We retrospectively analyzed the data from 63 newly diagnosed CP-CML patients treated with imatinib mesylate at a dose of 400 mg/day as frontline therapy. The clinical data and cytogenetic test results at diagnosis and during monitoring were collected. The cytogenetic monitoring adherence assessment rates were measured. A correlation between chromosome banding analysis (CBA) and FISH was performed. The CCyR assessed by FISH was defined as < 1% BCR-ABL1(+) nuclei. The Kaplan-Meier method was used for overall survival analysis and time-to-event estimates. RESULTS: The cytogenetic monitoring assessment adherence was 50.8% at 3 months, 93.5% at 6 months, 96.7% at 12 months, and 88.6% at 18 months. The Pearson correlation coefficient showed a significantly positive association (r = 0.84; P < .001) between CBA and FISH. The median follow-up duration after imatinib mesylate initiation was 60 months. A CCyR was achieved in 90.4% of patients within the first 18 months of therapy. At 3 months, 31 patients underwent a FISH evaluation, and 13 (41.9%) had achieved a CCyR. The patients who did not achieve a CCyR at 3 months had a significantly inferior probability of 5-year failure-free survival (38% vs. 94%; P = .001) and progression-free survival (80% vs. 100%; P = .043) compared with those with a CCyR. CONCLUSION: We found improved monitoring adherence compared with the previous reports of Latin American populations. In countries with a high incidence of failure for CBA and a lack of real-time polymerase chain reaction standardization, FISH is a sensitive monitoring tool. In our cohort, patients not achieving an early CCyR, as tested by FISH, were a poor prognosis subgroup with worse rates of failure-free survival and progression-free survival.

Impact of Aberrant Antigens in the Outcome of Patients with Acute Leukemia at a Referral Institution in Mexico City.

BACKGROUND: Patients with acute leukemia can express aberrant markers, defined as antigens that are normally restricted to a different lineage. The reported significance and frequency of these markers is inconclusive. We assessed the frequency and impact of aberrant markers in patients with acute leukemia in a referral institution in Mexico City. METHODS: We included 433 patients, diagnosed and treated between 2005 and 2015 in our institution. RESULTS: Aberrant markers were expressed in 128 patients (29.6%); CD13 and CD33 were the most frequent aberrant markers in patients with acute lymphoblastic leukemia, while CD7 and CD19 were the most frequent in patients with acute myeloid leukemia. In the univariate analysis, the group with aberrant markers had a lower disease-free survival when compared with the aberrant-free group (8 vs. 13 months) (p = 0.03). Aberrant expression of CD10, CD20, and CD33 correlated with a worse outcome in a statistically significant manner. In the multivariate analysis, male gender, lymphoid lineage, secondary leukemia, high risk at diagnosis, and the presence of aberrant markers had a significantly negative impact on disease-free survival. CONCLUSION: The use of more aggressive treatment strategies could be considered in patients with acute leukemia and an aberrant expression of CD10, CD20, and CD33.

Thalidomide and Dexamethasone Induction Therapy Until Best Response in Recently Diagnosed Patients with Multiple Myeloma: Results From a Pilot Study.

BACKGROUND: Novel therapies for multiple myeloma are not affordable for all healthcare systems. OBJECTIVES: The objectives of this study were to evaluate the response rates, overall survival, event-free survival, and toxicity of thalidomide and dexamethasone administered until best response in recently diagnosed patients with multiple myeloma. METHODS: All recently diagnosed multiple myeloma patients meeting the inclusion criteria received the same treatment with thalidomide and dexamethasone. RESULTS: We studied 28 patients. Overall response rate was 75%. Complete response, partial response, and very good partial response were 25.0, 32.1, and 17.9%, respectively. The most frequent adverse event related to therapy was neuropathy. Median overall survival was 66 months, and median event-free survival was 39 months (range, 27.6-50.4). Variables that negatively affected overall survival on multivariate analysis included the presence of extramedullary disease, t(14;16), and chromosome 13 deletion. CONCLUSIONS: Induction therapy with thalidomide and dexamethasone until obtaining the best response in patients with recently diagnosed multiple myeloma was a useful and safe strategy. It represents an alternative for patients with limited access to costly drugs.

Prognostic Factors, Response to Treatment, and Survival in Patients With Chronic Myeloid Leukemia in Blast Phase: A Single-Institution Survey.

INTRODUCTION: Data from 51 patients (23 women) with chronic myeloid leukemia (CML) in blast phase (BP) were analyzed in order to identify prognostic factors for complete hematologic response (CHR) and survival. PATIENTS AND METHODS: Forty-four patients experienced disease progression from chronic or accelerated phase, and 7 cases presented as CML-BP. Thirteen patients (25.5%) had extramedullary involvement at diagnosis, and 71% were myeloid BP. Clonal evolution was identified in 53% of the cases, and the abnormalities most frequently observed were isochromosome (17q), double Philadelphia chromosome, and trisomy 8. Forty-five patients received treatment: 60% chemotherapy (CT) alone and 40% CT plus tyrosine kinase inhibitors (TKI) or TKI alone; 42% of them experienced CHR. RESULTS: Median overall survival (OS) in patients whose disease responded to treatment was 7 months (95% confidence interval, 1.7-6.2 months), with a median disease-free survival of 5 months (95% confidence interval, 2.8-5.8 months). One out of 3 patients who underwent hematopoietic stem-cell transplantation remains alive. Multivariate analysis revealed that lymphoid BP and TKI therapy had a statistically significant positive impact as prognostic factors for CHR. In the multivariate analysis, age > 60 years, hemoglobin < 10 g/dL, and complex karyotype were statistically significant negative prognostic factors for OS. There was no statistical significant difference in OS between patients who received only CT (1988-2002) with those treated with CT plus TKI (2003-2013). CONCLUSION: This is the first study in Mexico to report prognostic factors associated with CHR and OS in patients with CML-BP.

[Primary adrenal malignacies]. / Tumores suprarrenales malignos primarios.

BACKGROUND: Primary adrenal malignancies are rare and have a dismal prognosis. We report our experience in both adrenocortical carcinomas and malignant pheochromocytomas who received medical care at our Institution between 1994 and 2009. MATERIAL AND METHODS: The data bases of hospital discharges, surgery and pathology were reviewed looking for patients with diagnosis of primary adrenal malignant tumors. Clinical presentation, laboratory and image characteristics, surgical details, histopathology findings and outcome were analyzed. RESULTS: A total of eight patients were identified, two men and six women with a mean age of 48.1 +/- 15.7 years (31-80). Six patients presented with adrenocortical carcinomas and two had malignant pheochromocytomas. Of the six cortical tumors four were functioning. Five were stage II, two were stage III and one was stage IV. All patients underwent surgery as initial treatment. Six patients underwent open and two, laparoscopic adrenalectomy. Three patients received adjuvant chemotherapy. In a mean follow up of 32 +/- 27 months, only three patients with stage II were alive and free of the disease. CONCLUSIONS: As in other series, primary adrenal carcinoma in our population proved to be a rare endocrine neoplasm with poor prognosis despite complete surgical resection. Treatment at initial stages provides better outcome.

[Acute myeloid leukemia in adults: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán from 2003 to 2008]. / Experiencia del INCMNSZ en pacientes adultos con leucemia mieloide aguda. Cohorte 2003-2008.

INTRODUCTION: Acute myeloid leukemia (AML) comprises a group of diseases with different biologic characteristics; despite knowledge improvements, these are not reflected in long term survival. OBJECTIVE: To describe characteristics of adults with AML in a hospital of Mexico City, their treatment response, complications and to evaluate survival related factors. MATERIAL AND METHODS: Cohort study. Between January 2003 and July 2008, patients with AML diagnosis were included (except promyelocitic). Treatment protocols used: 3 + 7, high doses of cytarabine and autologous bone marrow transplant as consolidation therapy. RESULTS: 53 patients were included. Median age: 44 years (15-79). At diagnosis: tumor lysis syndrome in 4/ 53 (7.5%), 3/51 (5.9%) with altered liver function test and hyperleukocytosis in 8/53 (15.1%). 46 patients had available cytogenetic and this was successful in 28/46 (60.8%), 12/28 (42.8%) had adverse cytogenetic; 16/28 (57.1%) intermediate risk and none was favorable. There were 2 losses during follow up, 7 patients did not receive chemotherapy with curative intent and 1 died at diagnosis. 43 patients received 3 + 7, 13.9% died during aplasia, complete remission was achieved in 27/43 (62.7%) and 10/43 (23.2%) were refractory to treatment. A second induction attempt was required in 39.5% (17/43). Median disease free survival (DFS) was 491 days (366-615), with a median follow up of 993 days (105-1744). The median overall survival (OS) was 531 days (312-749). Aplasia related mortality decreased (p = 0.09) between the actual cohort (13.9%) and the historical cohort (37%). CONCLUSIONS: Long term survival in AML patients remains poor despite improvements in diagnosis, classification, and treatment. In our institution, it is required to improve induction protocols and cytogenetic analysis in order to adequately choose the group of patients that could be benefit from stem cell transplant.

State-of-the-art in the management of chronic myelogenous leukemia in the era of the tyrosine kinase inhibitors: evolutionary trends in diagnosis, monitoring and treatment.

The treatment of patients with chronic myeloid leukemia (CML) continues to evolve rapidly as we gain better insights into the best monitoring strategies and as there is experience with the second generation tyrosine kinase inhibitors (TKI). Certain observations about CML and its clinical course remain relevant, such at its triphasic course and the prognostic value of the Sokal and Hasford scores. Other aspects of the disease including the most appropriate clinical monitoring and follow-up strategies and indications for changing therapy are evolving more rapidly. Best practice recommendations for monitoring of response have not only evolved over time but also affected by the availability and reliability of standard cytogenetics, FISH and molecular monitoring. Standard dose imatinib remains the best first-line therapy for most patients with first chronic phase CML. Patient and disease-related factors to evaluate when considering alternatives such as higher doses of imatinib, dasatinib, nilotinib and allogeneic transplant are discussed.

[Acute lymphoblastic leukemia: experience in adult patients treated with hyperCVAD and 0195 Protocol, at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Cohort 2003-2007]. / Experiencia del INCMNSZ en pacientes adultos con leucemia linfoide aguda. Cohorte 2003-2007 con esquemas de tratamiento Hiper-CVAD y Protocolo 0195.

INTRODUCTION: Despite therapeutic advances, acute lymphoblastic leukemia (ALL) in adults remains a disease with poor long term outcome and survival rates. Developing countries lack of information about this disease. On the other hand, infections are frequent complications related to mortality and some research studies do not show accurate rates of septic shock or other related factors. OBJECTIVE: To describe characteristics of adults with acute lymphoblastic leukemia, response to treatment, complications and to evaluate further survival related factors and to compare our experience with other reports of literature. MATERIAL AND METHODS: Between September 2003 to November 2007, the entire cohort of patients with diagnosis of ALL was included. The treatment regimens used were MDACC HyperCVAD (HCVAD) and 0195 (institutional regimen). RESULTS: Of 40 patients included with the diagnosis of ALL, 92% was B phenotype and 8%, T phenotype, with a median age of 27 years. The median follow up was 28.5 months. Initially, 14% showed central nervous system infiltration; of 51% with available cytogenetics, 16.7% was Philadelphia chromosome positive. There were 36 patients who received treatment: 13 received HCVAD and 23 the 0195 protocol; 78% achieved global complete remission, 85% for the patients with HCVAD and 74% with 0195. The induction death rate was 2.8%. The median disease-free survival was 11.6 months (IC 95%, 2.5-20.8 months) and overall survival was 15 months (IC 95%, 10.6-19.4 months). In 95% of patients, no prophylactic antibiotic therapy was used and treatment related death was 8.4% (2.8% during induction and 5.6% during the rest of treatment). Factors associated with worse survival rate were hyperleukocytosis, T phenotype and lack of early complete remission. During induction, grade 3 to 4 non hematopoietic toxicity was 17%. Incidence of neutropenic febrile episodes was 61% and septic shock was 11%. CONCLUSIONS: With HCVAD, we observed worse complete remission, disease-free survival and overall survival rates compared with the original MDACC reports. Chemotherapy related death rates are similar to other early reports, despite prophylactic antibiotic was not used during myelosuppression.

Angiogenesis in the bone marrow of patients with breast cancer.

PURPOSE: Pathologic angiogenesis has been correlated with tumor growth, dissemination, metastasis, and prognosis in solid tumors including breast cancer. Angiogenesis has also been implicated in the pathophysiology of, and shown to be a therapeutic target in tumors arising in the bone marrow. The status of angiogenesis in the bone marrow of breast cancer patients is unknown. The aim of this study was to estimate the extent of bone marrow angiogenesis in this subset of patients. EXPERIMENTAL DESIGN: We studied 42 women with breast cancer in whom a bone marrow biopsy was done. Bone marrow samples were sorted according to their infiltration status by breast cancer cells. In all bone marrow sections, blood vessels were highlighted by staining endothelial cells with an antibody directed against the CD34-related antigen. A hematopathologist blind to the status of infiltration of breast cancer did the bone marrow vessel count. RESULTS: Nineteen patients (45%) had bone marrow metastasis. The bone marrow microvessel density was significantly higher in patients with bone marrow metastases compared with patients without bone marrow metastases (P < 0.0005). Median bone marrow microvessel density was 2 for the negative bone marrow group, and 15 for the positive bone marrow group. An increased microvessel density was correlated with presence of disease at last follow-up. CONCLUSIONS: This is the first study showing that bone marrow microvessel density is significantly higher in breast cancer patients with bone marrow metastases, when compared with breast cancer patients without evidence of bone marrow metastatic disease. Further research is needed to shed light into the prognostic and therapeutic relevance of this finding.

Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma.

BACKGROUND: The goal of the current study was to evaluate the efficacy and toxicity of capecitabine in patients with nonresectable hepatobiliary carcinoma. METHODS: The authors performed a retrospective analysis of all patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), or gallbladder carcinoma (GBC) who were ever treated with oral capecitabine. The medical records of 116 patients with hepatobiliary carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between July 1998 and March 1999 were reviewed. RESULTS: A total of 63 patients were treated with capecitabine (37 with HCC, 18 with CCA, 8 with GBC). Capecitabine 1000 mg/m(2) was administered twice daily for 14 days. Treatment was repeated every 21 days. Each patient received 1-15 treatment cycles. Nine patients (14%)-11% of patients with HCC, 6% of patients with CCA, and 50% of patients with GBC-had either a complete response (CR) or a partial response. A CR was radiologically confirmed in one patient with HCC and in two patients with GBC. The median survival times were 10.1 months (95% confidence interval [CI], 4.5-15.7 months) for patients with HCC, 8.1 months (95% CI, 7.4-8.9 months) for patients with CCA, and 9.9 months (95% CI, 4.4-15.4 months) for patients with GBC. The most common toxicity was hand-foot syndrome (37%). Grade 3 thrombocytopenia occurred in 8% of patients with HCC. No other significant toxicities were observed. For all patients, response to treatment was positively correlated with survival and decline in tumor markers. CONCLUSIONS: Capecitabine was found to be safe for patients with hepatobiliary carcinoma, including those with cirrhosis. The antitumor activity of single-agent capecitabine was most pronounced in patients with GBC, was modest in patients with HCC, and was poor in patients with CCA.

The role of angiogenesis in the biology and therapy of myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by peripheral cytopenias in the setting of a normocellular or hypercellular bone marrow that morphologically shows trilineage dysplasia. Mechanisms of disease include pluripotent stem cell damage, abnormalities in proliferation, differentiation, and apoptosis leading to an ineffective hematopoiesis. A growing body of evidence support angiogenesis as having a key role in the pathophysiology of hematologic malignancies, including MDS. Knowledge and interest in angiogenesis and its interactions with proliferation and apoptosis have provided the rationale for the use of antiangiogenic drugs, such as thalidomide and its analogue CC5013, with hematologic improvement. Although the results are modest, other drugs with somewhat novel antiangiogenic mechanisms of action are under development, such as the vascular endothelial growth factor-receptor blocker SU5416, the antivascular endothelial growth factor antibody bevacizumab, arsenic trioxide, metalloproteinase inhibitors, such as AG3340, and farnesyl transferase inhibitor R115777. This review attempts to provide an overview of the evidence of increased angiogenesis and the status of drug development targeting angiogenesis in patients with MDS.