An Approach to Spatiotemporally Resolve Protein Interaction Networks in Living Cells.

Cells operate through protein interaction networks organized in space and time. Here, we describe an approach to resolve both dimensions simultaneously by using proximity labeling mediated by engineered ascorbic acid peroxidase (APEX). APEX has been used to capture entire organelle proteomes with high temporal resolution, but its breadth of labeling is generally thought to preclude the higher spatial resolution necessary to interrogate specific protein networks. We provide a solution to this problem by combining quantitative proteomics with a system of spatial references. As proof of principle, we apply this approach to interrogate proteins engaged by G-protein-coupled receptors as they dynamically signal and traffic in response to ligand-induced activation. The method resolves known binding partners, as well as previously unidentified network components. Validating its utility as a discovery pipeline, we establish that two of these proteins promote ubiquitin-linked receptor downregulation after prolonged activation.

Incorporation of extracorporeal photopheresis into a reduced intensity conditioning regimen in myelodysplastic syndrome and aggressive lymphoma: results from ECOG 1402 and 1902.

BACKGROUND: Extracorporeal photopheresis (ECP) is an immunomodulatory cellular therapy which has been shown to induce a tolerogenic state in patients with acute and chronic graft-vs-host disease. ECOG-ACRIN explored the activity of ECP as a part of a reduced intensity conditioning regimen in two multicenter trials in patients with MDS (E1902) and lymphomas (E1402). While both studies closed before completing accrual, we report results in 23 patients (17 MDS and 6 lymphoma). STUDY DESIGN AND METHODS: Patients received 2 days of ECP followed by pentostatin 4 mg/m2 /day for two consecutive days, followed by 600 cGy of total body irradiation prior to stem cell infusion. Immunosuppression for aGVHD was infusional cyclosporine A or tacrolimus and methotrexate on day +1, +3, with mycophenolate mofetil starting on day 100 for chronic GVHD prophylaxis. RESULTS: All patients engrafted, with median time to neutrophil and platelet engraftment of 15-18 days and 10-18 days respectively. Grade 3 or 4 aGVHD occurred in 13% and chronic extensive GVHD in 30%. CONCLUSIONS: These studies demonstrate that ECP/pentostatin/TBI is well tolerated and associated with adequate engraftment of neutrophils and platelets in patients with lymphomas and MDS.

Molecular mechanisms for vascular complications of targeted cancer therapies.

Molecularly targeted anti-cancer therapies have revolutionized cancer treatment by improving both quality of life and survival in cancer patients. However, many of these drugs are associated with cardiovascular toxicities that are sometimes dose-limiting. Moreover, the long-term cardiovascular consequences of these drugs, some of which are used chronically, are not yet known. Although the scope and mechanisms of the cardiac toxicities are better defined, the mechanisms for vascular toxicities are only beginning to be elucidated. This review summarizes what is known about the vascular adverse events associated with three classes of novel anti-cancer therapies: vascular endothelial growth factor (VEGF) inhibitors, breakpoint cluster-Abelson (BCR-ABL) kinase inhibitors used to treat chronic myelogenous leukaemia (CML) and immunomodulatory agents (IMiDs) used in myeloma therapeutics. Three of the best described vascular toxicities are reviewed including hypertension, increased risk of acute cardiovascular ischaemic events and arteriovenous thrombosis. The available data regarding the mechanism by which each therapy causes vascular complication are summarized. When data are limited, potential mechanisms are inferred from the known effects of inhibiting each target on vascular cell function and disease. Enhanced understanding of the molecular mechanisms of vascular side effects of targeted cancer therapy is necessary to effectively manage cancer patients and to design safer targeted cancer therapies for the future.

Cost-Effectiveness of Autologous Hematopoietic Stem Cell Transplantation for Elderly Patients with Multiple Myeloma using the Surveillance, Epidemiology, and End Results-Medicare Database.

In the past decade, the number of autologous hematopoietic stem cell transplants (Auto HSCT) for older patients with multiple myeloma (MM) has increased dramatically, as has the cost of transplantation. The cost-effectiveness of this modality in patients over age 65 is unclear. Using the Surveillance, Epidemiology, and End Results-Medicare database to create a propensity-score matched sample of patients over age 65 between 2000 and 2007, we compared the survival and cost for those who received Auto HSCT to those who did not undergo transplantation but survived at least 6 months after diagnosis, and we calculated an incremental cost-effectiveness ratio (ICER). Two hundred seventy patients underwent transplantation. Median overall survival from diagnosis in those who underwent transplantation was significantly longer than in patients who did not (58 months versus 37 months, P < .001). For patients living longer than 2 years, the median monthly cost during the first year was significantly different, but the middle and last year of life costs were similar. The median cost of the first 100 days after transplantation was $60,000 (range, $37,000 to $85,000). The resultant ICER was $72,852 per life-year gained. Survival after transplantation was comparable to that in those who underwent transplantation patients under 65 years and significantly longer than older patients who did not undergo transplantation. With an ICER less than $100,000/life-year gained, Auto HSCT is cost-effective when compared with nontransplantation care in the era of novel agents and should be considered, where clinically indicated, for patients over the age of 65.

Autologous stem cell transplant recipients tolerate haploidentical related-donor natural killer cell-enriched infusions.

BACKGROUND: In the setting of allogeneic stem cell transplantation (SCT), infusing natural killer (NK) cells from a major histocompatibility complex (MHC)-mismatched donor can mediate an antileukemic effect. The graft-versus-tumor effect after autologous stem cell transplantation (ASCT) may result in less disease relapse. STUDY DESIGN AND METHODS: We performed a Phase I clinical trial to assess the safety and feasibility of infusing distantly processed donor NK-enriched mononuclear cell (NK-MNC) infusions from a MHC haplotype-mismatched (haploidentical) donor to patients who recently underwent ASCT for a hematologic malignancy. On Day 1, peripheral blood MNCs were obtained by steady-state leukapheresis and sent from Boston to the Production Assistance for Cellular Therapies (PACT) facility at the University of Minnesota, where immunomagnetic depletion of CD3 cells was performed on Day 2. NK-MNC products were then returned to Boston on Day 2 for infusion on Day 3. Toxicity, cellular product characteristics, and logistic events were monitored. RESULTS: At a median of 90 days (range, 49-191 days) after ASCT, 13 patients were treated with escalating doses of NK-MNCs per kilogram from 10(5) to 2 × 10(7) . Adverse effects included Grade 2 rigors and muscle aches, but no Grade 3 or 4 events and no graft-versus-host disease or marrow suppression. One air courier delay occurred. NK-MNC products were viable with cytotoxic activity after transport. CONCLUSION: CD3-depleted, MHC-mismatched allogeneic NK-MNC infusions can be safely and feasibly administered to patients after ASCT after distant processing and transport, justifying further development of this approach.

Hematopoietic Stem-Cell Transplant Utilization in Relapsed/Refractory Hodgkin Lymphoma: A Population-Level Analysis of Statewide Claims Data.

PURPOSE: Although hematologic malignancies affect adults of all ages, few data exist on the real-world patterns of care for patients younger than 65 years in the United States. Understanding patterns of care from diagnosis through relapsed disease may provide insight about care across community and academic centers. We used a large statewide claims database to describe the path of Hodgkin lymphoma (HL) treatment among adults age < 65 years at diagnosis. METHODS: We defined a cohort of commercially insured patients with HL who underwent hematopoietic stem-cell transplantation (HSCT) from 2009 to 2013 in the Massachusetts All-Payer Claims Database (APCD). The primary goals of our study were to accurately identify patients and their treatment patterns who had relapsed/refractory HL and underwent HSCT. We also characterized time to treatment failure and overall survival. RESULTS: A total of 7,613 patients had International Classification of Diseases, Ninth Revision, diagnostic codes for HL. From our algorithm, we identified 117 patients as part of the final cohort who underwent autologous and/or allogeneic HSCT. Median age was 39.0 years and 50.4% were female. Initial therapy was identified for 68 of the 117 patients (58.1%). Most (> 74.4%) of the identified transplants were autologous, and 19 patients (16.2%) underwent allogeneic transplant, with or without prior autologous transplant. Of the 68 patients with initial therapy data, the median time to HSCT after completion of initial treatment was 223.5 days (Q1 = 151.5, Q3 = 414.5). CONCLUSION: We used the Massachusetts APCD to create a cohort of patients age < 65 years with relapsed/refractory HL. Our findings support the use of APCD for the large-scale analysis of patient characteristics, treatment patterns, and outcomes for young adult patients with hematologic malignancies.

Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996).

This phase 3 prospective randomized trial evaluated the efficacy and long-term safety of erythropoietin (EPO) with or without granulocyte colony-stimulating factor plus supportive care (SC; n = 53) versus SC alone (n = 57) for the treatment of anemic patients with lower-risk myelodysplastic syndromes. The response rates in the EPO versus SC alone arms were 36% versus 9.6%, respectively, at the initial treatment step, 47% in the EPO arm, including subsequent steps. Responding patients had significantly lower serum EPO levels (45% vs 5% responses for levels < 200 mU/mL vs > or = 200 mU/mL) and improvement in multiple quality-of-life domains. With prolonged follow-up (median, 5.8 years), no differences were found in overall survival of patients in the EPO versus SC arms (median, 3.1 vs 2.6 years) or in the incidence of transformation to acute myeloid leukemia (7.5% and 10.5% patients, respectively). Increased survival was demonstrated for erythroid responders versus nonresponders (median, 5.5 vs 2.3 years). Flow cytometric analysis showed that the percentage of P-glycoprotein(+) CD34(+) marrow blasts was positively correlated with longer overall survival. In comparison with SC alone, patients receiving EPO with or without granulocyte colony-stimulating factor plus SC had improved erythroid responses, similar survival, and incidence of acute myeloid leukemia transformation.

Myelodysplastic Syndrome in Patients with Gastro-Pancreatic Malignancies: A Case Series and Review of Literature.

Patients who develop one primary neoplasm are at increased risk for second cancers. Chemotherapeutic agents can result in DNA damage leading to clonal hematopoiesis, thereby causing myelodysplastic syndrome (MDS). Alkylating agents and topoisomerase inhibitors are most frequently implicated in therapy-related MDS. We report four patients with gastropancreatic malignancies (two with pancreatic adenocarcinoma and two with gastric adenocarcinoma) who developed MDS during or after the treatment of their primary gastrointestinal (GI) malignancies. Two of these patients were diagnosed with MDS during maintenance therapy with ramucirumab. To our knowledge, development of MDS in association with ramucirumab has not been previously reported in the literature. Our findings also suggest that with continued improvement in survival of patients with GI and pancreatic malignancies, more cases of treatment-related MDS might be identified.

Chloroma of the Bladder: A Case Report of Leukemia Progression Presenting as Hematuria.

Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute myelogenous leukemia (AML). The mass is composed of primitive myeloid cells that can occur in a variety of organs, most commonly the skin, lymph nodes, GI tract, bone, breast, and CNS. Involvement of the genitourinary tract is rare. Consensus on treatment of MS has not been established, but management typically involves systemic therapy, such as chemotherapy or allogeneic hematopoietic stem cell transplant as well as palliative local therapies such as radiation or surgery. Outcomes of MS using novel AML therapies, such as BCL-2 inhibitors or IDH inhibitors, remain undescribed. We describe a rare case of a 70-year-old man presenting with MS of the urinary bladder complicating known secondary AML (RUNX1 and IDH2 mutated). Prior to development of bladder MS, the patient had received decitabine, enasidenib, and venetoclax. Following diagnosis, he was treated with cytarabine and venetoclax. To our knowledge, this is the first case of bladder MS treated with a BCL-2 inhibitor.

Phase I and pharmacokinetic study of bortezomib in combination with idarubicin and cytarabine in patients with acute myelogenous leukemia.

PURPOSE: Proteasome inhibition results in cytotoxicity to the leukemia stem cell in vitro. We conducted this phase I study to determine if the proteasome inhibitor bortezomib could be safely added to induction chemotherapy in patients with acute myelogenous leukemia (AML). EXPERIMENTAL DESIGN: Bortezomib was given on days 1, 4, 8, and 11 at doses of 0.7, 1.0, 1.3, or 1.5 mg/m(2) with idarubicin 12 mg/m(2) on days 1 to 3 and cytarabine 100 mg/m(2)/day on days 1 to 7. RESULTS: A total of 31 patients were enrolled. The median age was 62 years, and 16 patients were male. Nine patients had relapsed AML (ages, 18-59 years, n = 4 and > or = 60 years, n = 5). There were 22 patients of > or = 60 years with previously untreated AML (eight with prior myelodysplasia/myeloproliferative disorder or cytotoxic therapy). All doses of bortezomib, up to and including 1.5 mg/m(2), were tolerable. Nonhematologic grade 3 or greater toxicities included 12 hypoxia (38%; 11 were grade 3), 4 hyperbilirubinemia (13%), and 6 elevated aspartate aminotransferase (19%). Overall, 19 patients (61%) achieved complete remission (CR) and three had CR with incomplete platelet recovery. Pharmacokinetic studies revealed that the total body clearance of bortezomib decreased significantly (P < 0.01, N = 26) between the first (mean +/- SD, 41.9 +/- 17.1 L/h/m(2)) and third (18.4 +/- 7.0 L/h/m(2)) doses. Increased bone marrow expression of CD74 was associated with CR. CONCLUSIONS: The combination of bortezomib, idarubicin, and cytarabine showed a good safety profile. The recommended dose of bortezomib for phase II studies with idarubicin and cytarabine is 1.5 mg/m(2).

Ethnic Differences in Hematologic Toxicity from Imatinib in Patients with Gastrointestinal Stromal Cell Tumor (GIST): Coincidence or a Real Phenomenon.

OBJECTIVES: There is a wide variability in the pharmacokinetics, pharmacodynamics and tolerance of anticancer drugs based on ethnicity. GIST is a rare cancer, (~1% of GI cancers). Imatinib is used in the neo-adjuvant, adjuvant and metastatic setting. The purpose of this study was to report the difference in hematologic toxicities to imatinib among different ethnicities when treated for GIST either in the adjuvant or metastatic setting. METHODS: We performed a retrospective study to collect data on patients with GIST (in any stage), who were on imatinib and presenting with grade 2 or more anemia, neutropenia and/or thrombocytopenia from July 1, 2005 to January 31, 2018. The degree of cytopenia was graded as per National Cancer Institute Common Toxicity criteria; version 4.0. We collected included age, gender, ethnicity, pathology, adverse effects-hematologic and non-hematologic, management of toxicities including dose modifications and administration of pegfilgrastim. RESULTS: Among 57 patients (median age 61 years, M: F=41:16 (F); ethnicities: White 65%, African-American (AA 19%, Asian 12% and Hispanic 4%), neutropenia (Grade 3 & 4) was seen in 6 patients (10%): 5 AA and 1 Asian. 45% of all AA patients developed neutropenia. Median absolute neutrophil count (ANC) nadir was 700/µL, median duration on drug prior to onset of neutropenia was 4.5 weeks and median duration of neutropenia was 4 weeks. One patient developed febrile neutropenia. Dose interruptions were needed in 3, dose-reductions in all patients, and 3 patients required pegfilgrastim. One patient had to discontinue imatinib, while one patient was escalated back to 400mg daily dose. CONCLUSION: This is the first study to examine ethnic variations in myelosuppression following imatinib in patients with GIST.

Clinicopathologic characteristics of secondary squamous cell carcinoma of head and neck in survivors of allogeneic hematopoietic stem cell transplantation for hematologic malignancies.

The risk of late complications including secondary malignancies is increased in long-term survivors of allogeneic hematopoietic stem cell transplants (HSCT). There is limited literature on the biological behavior and clinical features of squamous cell carcinoma (SCC) of head and neck post-HSCT. We present the clinical and pathologic characteristics on six patients who were diagnosed with SCC while in remission following an allogeneic HSCT. Median follow-up was 8 years. Five patients (83%) developed SCC of tongue and one developed esophageal SCC. Five patients had oral chronic graft-versus-host disease (cGvHD). The conventional risk factors of alcohol, tobacco, and human papillomavirus were absent. The most common presenting finding was the new-onset focal oral pain and ulcerated plaques clinically indistinguishable from a flare of their oral cGvHD lesions. We demonstrated that the SCC in three patients was of donor origin.

Daratumumab binds to mobilized CD34+ cells of myeloma patients in vitro without cytotoxicity or impaired progenitor cell growth.

BACKGROUND: The monoclonal antibody daratumumab, approved for treating myeloma, targets CD38, a protein on myeloma and also on CD34+ hematopoietic progenitor cells. Because mobilized CD34+ cells are critical for stem cell transplant, we investigated the in vitro activity of daratumumab on mobilized CD34+ cells from myeloma patients with no prior exposure to daratumumab. METHODS: We determined the number of CD38 molecules per CD34+ cell, and whether daratumumab bound to CD34+ cells, whether C1q bound to daratumumab-coated CD34+ cells and whether daratumumab-related complement-dependent cytotoxicity (CDC) occurred. We also examined CD34+ cell progenitor cell colony capacity in assays with pre-plating incubation of CD34+ cells with daratumumab alone or with daratumumab and the CD59 inhibitory antibody BRIC229, and also assessed CD34+ cell responses to increasing doses of daratumumab in caspase 3/7 activity assays. RESULTS: Although 75% of mobilized CD34+ cells co-express CD38, CD38 was minimally present on CD34+ cells compared to Daudi and KG-1 controls, C1q did not bind to daratumumab-coated CD34+ cells, and CDC did not occur. CD34+ cells incubated in complement-rich human serum with daratumumab alone or with daratumumab and BRIC229, and then plated in progenitor cell assays, produced similar numbers of colonies as controls. In progenitor cell assays with cryopreserved or fresh unselected or CD34-selected cells, daratumumab did not affect progenitor cell capacity, and in caspase 3/7 activity assays CD34+ cells were not affected by increasing doses of daratumumab. CONCLUSION: In vitro, daratumumab is not toxic to mobilized CD34+ progenitor cells from myeloma patients.

Antioxidant activity and polyphenol and procyanidin contents of selected commercially available cocoa-containing and chocolate products in the United States.

In the United States, commercially available foods, including cocoa and chocolate, are being marketed with statements referring to the level of antioxidant activity and polyphenols. For cocoa-containing foods, there has been no comprehensive survey of the content of these and other chemistries. A survey of cocoa and chocolate-containing products marketed in the United States was conducted to determine antioxidant activity and polyphenol and procyanidin contents. Commercially available samples consisted of the top market share products in each of the following six categories: natural cocoa, unsweetened baking chocolate, dark chocolate, semisweet baking chips, milk chocolate, and chocolate syrup. Composite samples were characterized using four different methods: oxygen radical absorbance capacity (ORAC), vitamin C equivalence antioxidant capacity (VCEAC), total polyphenols, and procyanidins. All composite lots were further characterized for percent nonfat cocoa solids (NFCS) and percent fat. Natural cocoas had the highest levels of antioxidant activities, total polyphenols, and procyanidins followed by baking chocolates, dark chocolates and baking chips, and finally milk chocolate and syrups. The results showed a strong linear correlation between NFCS and ORAC (R (2) = 0.9849), total polyphenols (R (2) = 0.9793), and procyanidins (R (2) = 0.946), respectively. On the basis of principal component analysis, 81.4% of the sample set was associated with NFCS, antioxidant activity, total polyphenols, and procyanidins. The results indicated that, regardless of the product category, NFCS were the primary factor contributing to the level of cocoa antioxidants in the products tested. Results further suggested that differences in cocoa bean blends and processing, with the possible exception of Dutching, are minor factors in determining the level of antioxidants in commercially available cocoa-containing products in the United States.

Cost Implications of Comorbidity for Autologous Stem Cell Transplantation in Elderly Patients with Multiple Myeloma Using SEER-Medicare.

Comorbidity is more common in older patients and can increase the cost of care by increasing toxicity. Using the SEER-Medicare database from 2000 to 2007, we examined the costs and life-year benefit of Auto-HSCT for MM patients over the age of 65 by evaluating the difference over time relative to comorbidity burden. One hundred ten patients had an Auto-HSCT in the early time period (2000-2003) and 160 in the late time period (2004-2007). Patients were divided by a Charlson Comorbidity Index (CCI) of 0 or greater than 1 (CCI1+). Median overall survival was 53.5 months for the late time period patients compared to 40.3 months for the early time period patients (p = 0.031). Median costs for CCI0 versus CCI1+ in the early period were, respectively, $70,900 versus $72,000 (100 d); $86,100 versus $98,300 (1 yr); and $139,200 versus $195,300 (3 yrs). Median costs for late period were, respectively, $58,400 versus $60,400 (100 d); $86,300 versus $77,700 (1 yr); and $124,400 versus $110,900 (3 yrs). Comorbidity had a significant impact on survival and cost among early time period patients but not among late time period patients. Therefore, older patients with some comorbidities can be considered for Auto-HSCT depending on clinical circumstances.

Impaired respiratory and skeletal muscle strength in patients prior to hematopoietic stem-cell transplantation.

STUDY OBJECTIVES: The primary aim was to determine if respiratory and skeletal muscle strength and submaximal exercise capacity were reduced in subjects prior to sibling- or unrelated-donor hematopoietic stem-cell transplantation (HSCT). DESIGN: Prospective observational study. SETTING: Tufts-New England Medical Center, a tertiary referral center in Boston, MA. PATIENTS: All patients (n = 56) undergoing either sibling- or unrelated-donor HSCT from January 1, 2002, to December 31, 2002. MEASUREMENTS: Demographic data, chemotherapy burden, pulmonary function tests (PFTs), maximal inspiratory muscle strength (PImax), maximal expiratory muscle strength (PEmax), dominant hand grip strength (GS), 6-min walk test (6MWT), and survival as of May 21, 2004. RESULTS: PImax was reduced to < 80% predicted in 42% of subjects and to < 60% predicted in 18% of subjects. PEmax was reduced to < 80% predicted in 89% of subjects and to < 60% of predicted in 80% of subjects. A significant correlation was observed between PImax and PEmax (r = 0.65, p < 0.0001). GS was reduced to < 80% predicted in 39% of subjects and < 60% predicted in 15% of subjects. The 6MWT was reduced to < 80% predicted in 58% of subjects and to < 60% predicted in 9.6% of subjects. Diffusing capacity of the lung for carbon monoxide (Dlco) was the only PFT that was significantly correlated with 6MWT distance (r = 0.44, p = 0.015). The mean calculated load of chemotherapy was 14.8 +/- 16.5 U (+/- SD). The mean time elapsed from date of hematologic diagnosis to date of HSCT was 874 +/- 1,109 days. The median survival of the cohort was 374 days (95% confidence interval, 177 to 665 days). Respiratory or skeletal muscle strength, 6MWT distance, or calculated burden of chemotherapy did not predict survival. CONCLUSIONS: Respiratory and skeletal muscle strength and submaximal exercise capacity are reduced in a significant percentage of patients prior to undergoing HSCT. These observations may help explain musculoskeletal weakness that has been reported in the posttransplant period.

Intensified induction chemotherapy in adult acute myeloid leukemia followed by high-dose chemotherapy and autologous peripheral blood stem cell transplantation: an Eastern Cooperative Oncology Group trial (E4995).

The feasibility of intensified therapy in adults < 61-years-old with de novo acute myeloid leukemia (AML) was evaluated by adding high-dose cytarabine (HDAC) to conventional induction therapy and in post-remission therapy prior to peripheral blood stem cell transplantation (PBSCT). Patients were treated with conventional induction therapy (daunorubicin days 1-3 and cytarabine days 1-7), followed by HDAC (2 gm/M2) every 12 h ( x 6) on days 8-10. Patients in complete remission (CR) with HLA-matched siblings were assigned to allogeneic PBSCT; the others received two courses of HDAC (3 gm/M2 every 12 h on days 1, 3, and 5) given 1 month apart. Peripheral blood stem cells were then harvested and infused after high-dose chemotherapy. Of 62 eligible, evaluable patients, 47 (76%) achieved CR. The mortality rate was 10% (6 patients); no deaths occurred during the two post-remission courses of HDAC. Fifteen patients were assigned to allogeneic PBSCT and 32 to autologous PBSCT. All surviving patients have been followed for more than 4 years. Including all patients scheduled to receive autoPBSCT in an intent-to-treat analysis, after a median 5-year follow-up the current, non-actuarial, four-year event-free and overall survival was 47% and 47%, respectively. Intensified induction therapy was associated with more toxicity than conventional induction therapy, and the CR rate did not improve. Nevertheless, intensive post-remission therapy was well tolerated, no treatment-related mortality occurred with autologous PBSCT, and disease-free survival and overall survival were lengthy.

GM-CSF and low-dose cytosine arabinoside in high-risk, elderly patients with AML or MDS.

Priming of leukemic cells with cytokines may enhance the efficacy of cell-cycle chemotherapy. In this study, we utilized these synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]), hydroxyurea, and low-dose cytosine arabinoside to treat elderly patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In a single-institution, retrospective study, we evaluated 94 treatments with concomitant hydroxyurea, cytosine arabinoside, and GM-CSF between the years of 1997 and 2003 in high-risk elderly patients with AML or MDS. A total of 80% of patients received all of the GM-CSF doses; 78% of patients received all of the cytosine arabinoside doses. Adverse events were minimal. No patient developed mucositis or alopecia. The most common adverse event was neutropenic fever, which was noted in 57% of patients. Twenty-one percent of patients remained neutropenic after treatment until death or relapse. Sixty-eight percent of patients reached an absolute neutrophil count of greater than 1000 microL in a median of 33.5 days. Our data show an overall response rate of 52%, with a complete response rate of 39% and a partial response rate of 13%. Overall, our study showed that low-dose cytosine arabinoside given by continuous infusion together with continuous infusion GM-CSF and hydroxyurea was well-tolerated and effective in treating elderly AML and MDS patients who were not eligible for standard induction therapy.

A unique case of relapsed B-acute lymphoblastic leukemia/lymphoma as an isolated omental mass.

B-acute lymphoblastic leukemia/lymphoma (B-ALL) is a neoplasm of precursor cells committed to the B-cell lineage. Extramedullary involvement is frequent, with particular predilection for the central nervous system, lymph nodes, spleen, liver, and testis. We report an unusual case of B-ALL relapsing as an isolated omental mass along with bone marrow involvement.