UTE-SENCEFUL: first results for 3D high-resolution lung ventilation imaging.

PURPOSE: This study aimed to develop a 3D MRI technique to assess lung ventilation in free-breathing and without the administration of contrast agent. METHODS: A 3D-UTE sequence with a koosh ball trajectory was developed for a 3 Tesla scanner. An oversampled k-space was acquired, and the direct current signal from the k-space center was used as a navigator to sort the acquired data into 8 individual breathing phases. Gradient delays were corrected, and iterative SENSE was used to reconstruct the individual timeframes. Subsequently, the signal changes caused by motion were eliminated using a 3D image registration technique, and ventilation-weighted maps were created by analyzing the signal changes in the lung tissue. Six healthy volunteers and 1 patient with lung cancer were scanned with the new 3D-UTE and the standard 2D technique. Image quality and quantitative ventilation values were compared between both methods. RESULTS: UTE-based self-gated noncontrast-enhanced functional lung (SENCEFUL) MRI provided a time-resolved reconstruction of the breathing motion, with a 49% increase of the SNR. Ventilation quantification for healthy subjects was in statistical agreement with 2D-SENCEFUL and the literature, with a mean value of 0.11 ± 0.08 mL/mL for the whole lung. UTE-SENCEFUL was able to visualize and quantify ventilation deficits in a patient with lung tumor that were not properly depicted by 2D-SENCEFUL. CONCLUSION: UTE-SENCEFUL represents a robust MRI method to assess both morphological and functional information of the lungs in 3D. When compared to the 2D approach, 3D-UTE offered ventilation maps with higher resolution, improved SNR, and reduced ventilation artifacts.

Grade of retraction and tendon thickness correlates with MR-spectroscopically measured amount of fatty degeneration in full thickness supraspinatus tears.

BACKGROUND: The amount of fatty degeneration (FD) has major impact on the clinical result and cuff integrity after rotator cuff repair. A quantitative analysis with magnet resonance imaging (MRI) spectroscopy was employed to analyze possible correlation of FD with tendon retraction, tendon thickness and patients' characteristics in full thickness supraspinatus tears. METHODS: Forty-two patients with full-thickness supraspinatus tears underwent shoulder MRI including an experimental spectroscopic sequence allowing quantification of the fat fraction in the supraspinatus muscle belly. The amount of fatty degeneration was correlated with tendon retraction, tendon thickness, patients' age, gender, smoker status, symptom duration and body mass index (BMI). Patients were divided in to three groups of retraction (A) 0-10 mm (n=), (B) 11-20 mm (n=) and (C) < 21 mm (n=) and the means of FD for each group were calculated. RESULTS: Tendon retraction (R = 0.6) and symptom duration (R = 0.6) correlated positively, whereas tendon thickness correlated negatively (R = - 0.6) with the amount of FD. The fat fraction increased significantly with tendon retraction: Group (A) showed a mean fat mount of 3.7% (±4%), group (B) of 16.7% (±8.2%) and group (C) of 37.5% (±19%). BMI, age and smoker-status only showed weak to moderate correlation with the amount of FD in this cohort. CONCLUSION: MRI spectroscopy revealed significantly higher amount of fat with increasing grade of retraction, symptom duration and decreased tendon thickness. Thus, these parameters may indirectly be associated with the severity of tendon disease.

Quantitative MRI comparison of multifidus muscle degeneration in thoracolumbar fractures treated with open and minimally invasive approach.

BACKGROUND: Minimally invasive pedicle screw fixation has less approach-related morbidity than open screw placement and is allegedly less traumatizing on paravertebral muscles, as there is no requirement to mobilize and retract the adjacent muscle portion. The approach-related long-term effects to the morphology of the paravertebral muscles are unknown. The purpose of this study was to compare the long-term amount of fatty degeneration of the multifidus muscle in patients treated with a classical open or a minimally invasive approach. METHODS: Fourteen Patients meeting inclusion criteria were selected. In all patients a singular fracture of the thoracolumbar spine with a two-level posterior instrumentation was treated, either using an open approach or a minimally invasive approach. All patients underwent quantitative MRI spectroscopy for quantification of the fatty degeneration in the multifidus muscle as a long-term proof for muscle loss after minimum 4-year follow-up. Clinical outcome was assessed using Oswestry Low Back Pain Disability Questionnaire, SF-36 and VA-scale for pain. RESULTS: The minimally invasive approach group failed to show less muscle degeneration in comparison to the open group. Total amount of fatty degeneration was 14.22% in the MIS group and 12.60% in the open group (p = 0.64). In accordance to MRI quantitative results there was no difference in the clinical outcome after a mean follow up of 5.9 years (±1.8). CONCLUSION: As short-term advantages of minimal invasive screw placement have been widely demonstrated, no advantage of the MIS, displaying a significant difference in the amount of fatty degeneration and resulting in a better clinical outcome could be found. Besides the well-known short-term advantage of minimally invasive pedicle screw placement, a long-term advantage, such as less muscle degeneration and thus superior clinical results, compared to the open approach could not be shown.

Myocardial lipid content in Fabry disease: a combined 1H-MR spectroscopy and MR imaging study at 3 Tesla.

BACKGROUND: Fabry disease is characterized by a progressive deposition of sphingolipids in different organ systems, whereby cardiac involvement leads to death. We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by 1H magnetic resonance spectroscopy (MRS) at 3 Tesla. METHODS: Myocardial lipid content was quantified in vivo by 1H-MRS in 30 patients (12 male, 18 female; 18 patients treated with enzyme replacement therapy) with genetically proven Fabry disease and in 30 healthy controls. The study protocol combined 1H-MRS with cardiac cine imaging and LGE MRI in a single examination. RESULTS: Myocardial lipid content was not significantly elevated in Fabry disease (p = 0.225). Left ventricular (LV) mass was significantly higher in patients suffering from Fabry disease compared to controls (p = 0.019). Comparison of patients without signs of myocardial fibrosis in MRI (LGE negative; n = 12) to patients with signs of fibrosis (LGE positive; n = 18) revealed similar myocardial lipid content in both groups (p > 0.05), while the latter showed a trend towards elevated LV mass (p = 0.076). CONCLUSIONS: This study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by 1H-MRS. Finally, the authors share the opinion that a comprehensive cardiac examination including three subsections (LGE; 1H-MRS; T1 mapping), could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.

Targeting leukemia stem cells: which pathways drive self-renewal activity in T-cell acute lymphoblastic leukemia?

T-Cell acute lymphoblastic leukemia (t-all) is a malignancy of white blood cells, characterized by an uncontrolled accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and crowd into the bone marrow, preventing it from making normal blood cells and spilling out into the bloodstream. Recent studies suggest that only discrete cell populations that possess the ability to recreate the entire tumour might be responsible for the initiation and propagation of t-all. Those unique cells are commonly called "cancer stem cells" or, in the case of hematopoietic malignancies, "leukemia stem cells" (lscs). Like normal hematopoietic stem cells, lscs are thought to be capable of self-renewal, during which, by asymmetrical division, they give rise to an identical copy of themselves as well as to a daughter cell that is no longer capable of self-renewal activity and represents a more "differentiated" progeny. Here, we review the main pathways of self-renewal activity in lscs, focusing on their involvement in the maintenance and development of t-all. New stem cell-directed therapies and lsc-targeted agents are also discussed.

Comprehensive microRNA expression profiling of the hematopoietic hierarchy.

The hematopoietic system produces a large number of highly specialized cell types that are derived through a hierarchical differentiation process from a common stem cell population. miRNAs are critical players in orchestrating this differentiation. Here, we report the development and application of a high-throughput microfluidic real-time quantitative PCR (RT-qPCR) approach for generating global miRNA profiles for 27 phenotypically distinct cell populations isolated from normal adult mouse hematopoietic tissues. A total of 80,000 RT-qPCR assays were used to map the landscape of miRNA expression across the hematopoietic hierarchy, including rare progenitor and stem cell populations. We show that miRNA profiles allow for the direct inference of cell lineage relations and functional similarity. Our analysis reveals a close relatedness of the miRNA expression patterns in multipotent progenitors and stem cells, followed by a major reprogramming upon restriction of differentiation potential to a single lineage. The analysis of miRNA expression in single hematopoietic cells further demonstrates that miRNA expression is very tightly regulated within highly purified populations, underscoring the potential of single-cell miRNA profiling for assessing compartment heterogeneity.

Reproducibility of non-contrast enhanced multi breath-hold ultrashort echo time functional lung MRI.

PURPOSE: To evaluate the intraindividual reproducibility of functional lung imaging using non-contrast enhanced multi breath-hold 3D-UTE MRI. METHODS: Ten healthy volunteers underwent non-contrast enhanced 3D-UTE MRI at three time points for same-day and different-day measurements employing a stack-of-spirals trajectory at 3 T. At each time point, inspiratory and expiratory breathing states were acquired for tidal and deep breathing, each within a single breath-hold. For functional image analysis, fractional ventilation (FV) was calculated pixelwise after image registration from the MR signal change. To decouple FV from breathing depth, the individual lung volume was used for volume adjustment (rFV). Reproducibility evaluation was performed in eight lung segments. Statistical analyses included two way mixed intraclass correlation (ICC), sign-test, Friedman-test and modified Bland-Altman analyses. RESULTS: FV from tidal breathing showed an ICC of 0.81, a bias of 1.3% and an interval of confidence (CI) ranging from -67.1 to 69.6%. FV from deep breathing was higher reproducible with an ICC of 0.92 (bias, -0.2%; CI, -34.2 to 33.7%). Following volume adjustment, reproducibility of rFV for tidal breathing improved (ICC, 0,86; bias, 2.0%; CI, -34.3 to 38.3%), whereas it did not bear significant benefits for deep breathing (ICC, 0.89; bias, 2.8%; CI, -24.9 to 30.5%). Reproducibility was independent from the examination day. CONCLUSION: Non-contrast-enhanced multi breath-hold 3D-UTE MRI allows for highly reproducible ventilation imaging.

Quantitative myocardial perfusion imaging with a MR cold pressor test.

The response of myocardial blood flow to sympathetic stimulation with cold is modulated by endothelium-related factors. As endothelial dysfunction is an early step in patients with coronary artery disease, the aim of this study was to establish a cold pressor test (CPT) setting for quantitative analysis of myocardial perfusion in a MR scanner. First pass perfusion studies were performed in 10 healthy volunteers using a 1.5 T MR scanner with a multislice steady state free precession perfusion trueFISP sequence in prebolus technique (1 cc/4 cc gadobenate dimeglumine). MR-CPT was established using an over head ice-water bath of the left hand. First pass perfusion imaging was started after 1 min to assure an adequate stimulus followed by a second series after 15 min to evaluate the rest perfusion. After motion correction images were segmented with an adapted, automated tool, myocardial contours were determined. Perfusion was quantitatively evaluated after contamination and baseline correction by deconvolution with the arterial input function using an exponential function model as residuum. All data could be evaluated. Mean myocardial perfusion rose from 0.61 ± 0.22 cc/g/min at rest to 1.15 ± 0.34 cc/g/min under CPT. MR myocardial perfusion values show a comparable increase under CPT as published positron emission tomography data. Consequently, CPT for the presence of endothelial dysfunction is feasible in the MR environment.

Liquid-chromatographic profiling of Saponinum album (Merck).

Saponinum album (Merck) is a complex composite of triterpene saponins. It was shown that Saponinum album (Merck) dramatically enhances the toxicity of the N-glycosylase saporin from the seeds of Saponaria officinalis L. as well as the toxicity of a saporin based anti-tumor toxin. This study was intended to chromatographically profile the saponins present in Saponinum album (Merck) in order to identify saponins that determine the cytotoxicity enhancing properties of Saponinum album (Merck) on saporin. For this purpose a liquid-chromatographic profiling (HPLC) followed by ESI-TOF-MS analysis and evaluation of cytotoxicity enhancer effects of saponins from Saponinum album (Merck) was performed. This is the first study describing a liquid-chromatographic profiling of saponins from Saponinum album (Merck). Ten different saponins were isolated. There was a lot of variation observed in the cytotoxicity enhancing properties of different isolated saponins, 8 out of 10 isolated saponins showed an enhancer effect on the toxicity of saporin. Based on these results it was concluded that the cytotoxicity enhancer effect of Saponinum album (Merck) is not attributable to a single, activity determining saponin.

Non-contrast pulmonary perfusion MRI in patients with cystic fibrosis.

PURPOSE: This study aimed to assess the feasibility of Self-gated Non-Contrast-Enhanced Functional Lung (SENCEFUL) MRI for detection of pulmonary perfusion deficits in patients with cystic fibrosis. METHODS: Twenty patients with cystic fibrosis and 20 matched healthy controls underwent SENCEFUL-MRI at 1.5 T with reconstruction of perfusion and perfusion phase maps (i.e. comparable to pulse wave delays). Four blinded readers rated both types of maps separately followed by simultaneous assessment thereof. Perfusion phase data was plotted in histograms and a Peak-to-Offset ratio was calculated for comparison to subjective scoring and correlation (Spearman) to lung function parameters. Sensitivity, specificity and positive and negative predictive values were calculated for subjective scoring and Peak-to-Offset ratios. Intraclass correlation (ICC) was used to assess the interrater agreement. RESULTS: Readers attributed pathological ratings 2.2-3.5 times more frequently to the CF-group. The sensitivity with regard to a correct assignment to CF was similar between ratings (perfusion only vs. perfusions phase only vs. simultaneous assessment: 0.54-0.56), while specificity increased from 0.75 to 0.85 for simultaneous assessment. ICC was 0.77-0.84 for subjective scoring. ROC-analysis of Peak-to-Offset ratios on a mean per-subject basis revealed a sensitivity of 0.75 and specificity of 0.85 (PPV 0.83, NPV 0.77). Functional pulmonary parameters indicative of bronchial obstruction and Peak-to-Offset ratios showed positive correlation (FEV1: 0.77; FEF75: 0.76). CONCLUSIONS: SENCEFUL-MRI bears the potential for monitoring CF including disease-associated patterns of altered pulmonary perfusion. The proposed Peak-to-Offset ratio derived from pulmonary perfusion phase measurements could represent an objective future marker for perfusion impairment.

Enhancement of cytotoxicity of ribosome-inactivating-protein type I by saponinum album is not based on stimulation of phagocytosis.

Saponinum album, a mixture of triterpenoic saponins derived from Gypsophila species, led to an increased internalization of agrostin, a ribosome-inactivating-protein (RIP) type I in U-937 cells differentiated with interferon-gamma or phorbol myristate acetate. Treatment with agrostin only showed no cytotoxicity. It was hypothesized that saponinum album stimulated phagocytosis and by that the uptake of agrostin. For this purpose phagocytosis experiments with Alexa-Fluor-488-labelled 1-microm amino-latex beads and FITC-labelled Escherichia coli (K-12 strain) were performed. The results indicated no stimulation of phagocytosis by treatment with saponinum album.

The bulk chromatin structure of a murine transgene does not vary with its transcriptional or DNA methylation status.

The DNA methylation status of HRD, a murine transgene, can be controlled by the genetic background upon which it is carried. We found the transgene to be transcribed in competent tissues only when undermethylated. Chromatin structure over the transgene was assayed by nuclear accessibility with DNase I, MspI, and PstI. While the transgene was up to fivefold more resistant to MspI when methylated than when not methylated, we observed no such difference with DNase I or PstI. We suggest that methyl-CpG-binding proteins are responsible for the difference observed with MspI, but that the chromatin structures are otherwise similarly compacted. Methylation could, therefore, play a regulatory role in gene expression beyond that which can be accomplished by bulk chromatin structure alone.

Influence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrate.

We have previously described a line of transgenic mice with multiple head-to-tail copies of an artificial V-J recombination substrate and have shown that the methylation of this transgene is under the control of a dominant strain-specific modifier gene, Ssm-1. When the transgene array is highly methylated, no recombination is detectable, but when it is unmethylated, V-J joining is seen in the spleen, bone marrow, lymph nodes, and Peyer's patches but not in the thymus or nonlymphoid tissues, including brain tissue. Strikingly, in mice with partially methylated transgene arrays, rearrangement preferentially occurs in hypomethylated copies. Therefore, V-J recombination is negatively correlated with methylated DNA sequences. In addition, it appears that recombination occurs randomly between any two recombination signal sequences within the transgene array. This lack of target preference in an unselectable array of identical targets rules out simple mechanisms of one-dimensional tracking of a V(D)J recombinase complex.

Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas.

Ahi-1 (Abelson helper integration site 1) is a novel gene frequently activated by provirus insertional mutagenesis in murine leukemias and lymphomas. Its involvement in human leukemogenesis is demonstrated by gross perturbations in its expression in human leukemia cells, particularly in cutaneous T-cell lymphoma cell lines where increases in AHI-1 transcripts of 40-fold are seen. To test directly whether deregulated expression of AHI-1 contributes to their transformed properties, knockdown of AHI-1 expression in Hut78 cells, a cell line derived from a patient with Sezary syndrome (SS), was performed using retroviral-mediated RNA interference. Retroviral-mediated suppression specifically inhibited expression of AHI-1 and its isoforms in transduced cells by 80% and also reduced autocrine production of interleukin (IL)-2, IL-4 and tumor necrosis factor-alpha (TNFalpha) by up to 85%. It further significantly reduced their growth factor independence in vitro and the ability to produce tumors in immunodeficient mice. Interestingly, aberrant expression of AHI-1, particularly truncated isoforms, was present in CD4+CD7- Sezary cells from some patients with SS. Elevated expression of IL-2 and TNFalpha was also found in these cells. These findings provide strong evidence of the oncogenic activity of AHI-1 in human leukemogenesis and demonstrate that its deregulation may contribute to the development of SS.

Regulation of PI3K signaling in T-cell acute lymphoblastic leukemia: a novel PTEN/Ikaros/miR-26b mechanism reveals a critical targetable role for PIK3CD.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, and T-ALL patients are prone to early disease relapse and suffer from poor outcomes. The PTEN, PI3K/AKT and Notch pathways are frequently altered in T-ALL. PTEN is a tumor suppressor that inactivates the PI3K pathway. We profiled miRNAs in Pten-deficient mouse T-ALL and identified miR-26b as a potentially dysregulated gene. We validated decreased expression levels of miR-26b in mouse and human T-ALL cells. In addition, expression of exogenous miR-26b reduced proliferation and promoted apoptosis of T-ALL cells in vitro, and hindered progression of T-ALL in vivo. Furthermore, miR-26b inhibited the PI3K/AKT pathway by directly targeting PIK3CD, the gene encoding PI3Kδ, in human T-ALL cell lines. ShRNA for PIK3CD and CAL-101, a PIK3CD inhibitor, reduced the growth and increased apoptosis of T-ALL cells. Finally, we showed that PTEN induced miR-26b expression by regulating the differential expression of Ikaros isoforms that are transcriptional regulators of miR-26b. These results suggest that miR-26b functions as a tumor suppressor in the development of T-ALL. Further characterization of targets and regulators of miR-26b may be promising for the development of novel therapies.

Enhancement of cytotoxicity of lectins by Saponinum album.

Saponinum album, a mixture of saponins with an aldehyde function bound at C4 from Gypsophila species, increased the cytotoxicity of lectins like agrostin and saporin by enhancing its penetration through the cell membrane. The effect was attenuated by latrunculin, an inhibitor of endocytosis, and by bafilomycin, an inhibitor of transport from early to late endosomes and lysosomes. In contrast, the effect was not influenced by brefeldin A that causes dissolution of the Golgi stacks and by the addition of different monosaccharides. The toxicity of other peptidic toxins was only slightly enhanced by the saponins indicating a specific interaction between lectins and saponins present in Caryophyllaceae.

Rearrangement and expression of immunoglobulin genes in transgenic mice.

Transgenic mice are discussed which carry a rearrangement test transgene. The methylation status of the transgene varies, depending on the background mouse strain. When the transgene is bred into the C57BL/6 strain, it is completely methylated and not rearranged in lymphoid organs. After several generations of crossing into DBA/2 or SJL the transgene becomes unmethylated and rearranges at high frequency. A strain specific modifier of DNA methylation (Ssm-1) was mapped close to the Friend virus susceptibility locus (Fv-1) on mouse chromosome 4. Rearranged transgenes from spleen, bone marrow and thymus of adult mice or fetal liver were cloned and sequenced. A great variety of joints was found, with about 1/3 being in the correct reading frame. Small deletions into the V- and J-coding ends as well as N region additions contributed to the variability. The fetal joints showed no N regions. Since no functional immunoglobulin (Ig) gene can be created from this artificial test gene, the data indicate that the rearrangement mechanism of the fetus differs from that of the adult.

Biologic and immunohistochemical analysis of macrophage interleukin- 1 alpha, - 1 beta, and tumor necrosis factor production during the peritoneal exudative response.

The present study examined changes in lipopolysaccharide (LPS)-induced interleukin 1 (IL-1) and tumor necrosis factor (TNF) production by murine peritoneal macrophages during the chronic exudative response to Freund's complete adjuvant (CFA). Macrophages were isolated by peritoneal lavage and adherence at intervals over a 32 day period following i.p. injection of CFA. Optimal culture conditions for IL-1 and TNF production were predetermined, and it was found that IL-1 production was profoundly impaired at densities of above 150 cells/mm2, whereas TNF synthesis was more resistant to density effects. Using optimal conditions, we observed a sequential appearance of monokines. On day 0 there was minimal IL-1 production and no detectable TNF production. By days 4-7, IL-1 production reached maximum levels with a steady decline to baseline by day 32. TNF production steadily increased after day 2, reached maximal levels by days 16-20, and then partly declined by day 32. These findings were supported by kinetic analyses at specified days. When related to exudative events, it appeared that maximal IL-1 was associated with the recruitment stage of the reaction, whereas TNF production was associated with the established exudate. Immunohistochemical analysis revealed that TNF production could be related to the proportion of macrophages with cytoplasmic TNF expression. In contrast, IL-1 alpha and -1 beta expression was comparable among populations with 85-100% of cells showing cytoplasmic expression 6 hr after LPS stimulus. Whereas cytoplasmic IL-1 alpha persisted for the 18 hr study period, IL-1 beta disappeared from many adjuvant recruited cells. Our findings suggest that monokine production is orchestrated during macrophage recruitment and activation at sites of chronic inflammation.

Diagnosis and treatment of Helicobacter pylori infection among California Medicare patients.

BACKGROUND: Antibiotic treatment of Helicobacter pylori infection in active peptic ulcer disease has been demonstrated to speed ulcer healing, reduce the risk of rebleeding, and prevent long-term recurrence. The objective of this study was to determine whether Medicare patients with peptic ulcer disease who are admitted to acute care hospitals are being tested or treated for H pylori infection as recommended by a National Institutes of Health consensus panel. METHODS: The study was designed as a retrospective medical records survey. From the Medicare National Claims History File, all persons 65 years and older admitted to California fee-for-service hospitals for peptic ulcer disease in 1994 were identified. A random sample of 600 claims was selected for review. After exclusions, 524 patients were eligible for study. The main outcome measures were (1) the proportion of patients who were tested for H pylori infection by 1 of the 5 available methods (histopathologic study, urease assay, microbiologic culture, serum antibody testing, or urea breath test) and (2) the proportion who were treated with antibiotics (amoxicillin, tetracycline, clarithromycin, or metronidazole) for H pylori infection. RESULTS: Thirty-nine percent of patients with peptic ulcer disease were tested for H pylori infection and 3% were treated empirically. Only 47% of the patients who had a positive diagnostic test result for H pylori were treated with antibiotics. CONCLUSION: Because diagnosis and treatment of H pylori infection has been demonstrated to improve outcomes and decrease expenses, the data indicate a substantial opportunity to improve the care of elderly Medicare patients with peptic ulcer disease.

Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity.

Burkitt and Burkitt-like lymphomas are rapidly growing tumors which require specialized therapy. Although intensive, multi-agent regimens have been effective in children, results are more variable in adults. Magrath et al. previously described a regimen that was highly effective in children and young adults. This phase II study of a modified Magrath regimen was designed to assess its efficacy in older adults and reduce treatment-related toxicity. Fourteen patients with Burkitt/Burkitt-like lymphoma and median age of 47 years were stratified into two categories: low-risk (normal LDH and a single focus of disease measuring less than 10 cm, 3 patients) and high risk (all other, 11 patients). Low-risk patients received three cycles of modified CODOX-M (cyclophosphamide, doxorubicin, adriamycin, vincristine with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate, regimen A). High-risk patients received four alternating cycles of regimens A and B (A-B-A-B). Regimen B consisted of ifosfamide, cytarabine, etoposide and intrathecal methotrexate (IVAC). The modified treatment regimen was associated with no grade 3/4 neuropathy and only one episode of grade 3/4 mucositis. All patients completed protocol therapy and there were no treatment-related deaths. Twelve patients (86%, 90% CI: 61 97%) achieved a complete response; 1 patient achieved a PR and 1 patient died of progressive disease. Nine patients (64%) are alive and disease free at a median follow-up of 29 months. This modified Magrath regimen is effective and well-tolerated in a representative group of older adult patients.