Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer.

PURPOSE: To evaluate the feasibility of allogeneic peripheral-blood progenitor-cell (PBPC) transplantation and to assess graft-versus-tumor effects in patients with metastatic breast cancer. PATIENTS AND METHODS: Ten patients with metastatic breast cancer that involved the liver or bone marrow were treated with high-dose chemotherapy and allogeneic PBPC transplantation. The median age was 42 years (range, 29 to 55). The median number of metastatic sites was three (range, one to five). The conditioning regimen was cyclophosphamide (6,000 mg/m2), carmustine (BCNU; 450 mg/m2), and thiotepa (720 mg/m2) (CBT regimen). Patients received graft-versus-host disease (GVHD) prophylaxis using cyclosporine- or tacrolimus-based regimens. RESULTS: All patients had engraftment and hematologic recovery. Three patients developed grade > or = 2 acute GVHD and four patients had chronic GVHD. After transplantation, one patient was in complete remission (CR), five achieved a partial remission (PR), and four had stable disease (SD). In two patients, metastatic liver lesions regressed in association with skin GVHD after withdrawal of immunosuppressive therapies. The median follow-up time was 408 days (range, 53 to 605). The median progression-free survival duration was 238 days (range, 53 to 510). CONCLUSION: We conclude that allogeneic PBPC transplantation is a feasible procedure for patients with poor-risk metastatic breast cancer. The regression of tumor associated with GVHD provides suggestive clinical evidence that graft-versus-tumor effects may occur against breast cancer. Compared with autologous transplantation, allogeneic PBPC transplantation is associated with the additional risks of GVHD and related infections. Allogeneic transplantation should only be performed in the context of clinical trials and its ultimate role requires demonstration of improved progression-free survival.

Functional and scintigraphic evaluation of the silent adrenal mass.

Seven patients with unilateral and one patient with bilateral and asymmetric (R greater than L) incidentally discovered adrenal mass abnormalities depicted by computed tomography (CT) were studied by 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy. There was marked lateralization of NP-59 uptake to the side of the mass lesion in the seven patients with unilateral masses and prominent asymmetric, (R greater than L) bilateral uptake in the patient with bilateral masses despite the fact that there were no obvious abnormalities of adrenocortical or adrenomedullary function as determined from peripheral blood and 24-hr urinary hormone measurements. Simultaneous bilateral adrenal vein catheterization (AVC) was employed to measure the levels of hormone effluent from the adrenal cortex and medulla and in all instances the cortisol concentrations were greatest from the side of the mass lesion in those patients with unilateral masses and from the larger of the two adrenals in the patient with bilateral adrenal masses. Thus, there was congruence between the anatomic (CT) and functional (NP-59 scintigraphy and AVC) investigations that depicted asymmetry of the adrenal glands which were not associated with abnormalities of overall adrenal function or hypothalamic-pituitary-adrenal axis integrity.

Hepatosplenic candidiasis. A manifestation of chronic disseminated candidiasis.

Much progress has been made over the last decade in diagnosing and treating CDC, a chronic and debilitating infection that interferes with the delivery of intensive cytotoxic chemotherapy in patients with leukemia. The use of fluconazole prophylaxis in these patients has decreased the incidence of CDC dramatically. The greatest future challenges are gaining a better understanding of its pathophysiology, and the continued development of effective diagnostic and therapeutic strategies to treat this unusual manifestation of systemic candidiasis.

Median and spatial low-pass filtering in ultrasonic computed tomography.

To reduce noise- and reconstruction-related artifacts in ultrasound computed tomography, the use of combined median and Hamming-weighted spatial low-pass filtering is evaluated. The evaluation of the reconstruction filters uses both computer-generated projections of a known object with the least mean-square error criterion as well as a more subjective evaluation of conventional ultrasonic attenuation and speed of sound images.

Diagnostic ultrasound in the evaluation of patients with gynecologic cancer.

In the early 1960's, obstetricians realized the usefulness of diagnostic ultrasonography and were largely responsible for much of the early development and advancement of the ultrasonic technique. Recently gray scale ultrasonography has resulted in the ability to conclusively differentiate solid from cystic masses. Research is currently underway regarding tissue identification based on ultrasonic patterns. The combined use of ultrasonic instrumentation and computers may some day enable the ultrasonographer to identify specific tissues within the body. Fine needle aspiration biopsy in combination with cross-sectional ultrasonic scanning in some cases circumvents the need for repeat laparotomy to obtain tissue for histologic diagnosis.

The detection and diagnosis of early, occult and minimal breast cancer.

Radical mastectomy as originally conceived at the turn of the century consisted of complete removal of the breast tissue, the overlying skin, the pectoral muscles, the intervening lymphatics and the axillary lymph nodes. The aim was logical but initially the results were poor. Only 41% of the 76 patients in Halsted's original series were without disease at the end of 3 years. The principal reason for this was the advanced stage of disease in the patients selected for treatment. By contrast, Gilbertsen, using clinical examination alone, surveyed women 45 years of age or older and found that of 32 patients with breast cancers detected by the screening procedure, 24 had no axillary lymph node involvement. The absolute 5-year survival rate of this group was 96%, which approaches the anticipated survival of comparable women free of breast cancer. Those with positive lymph nodes had an absolute survival rate of 75% at 5 years. Further, of 13 patients observed for 10 years, the survival rate for those without node involvement was 90% and for patients with node involvement was 33%. Patients treated at the Barnes Hospital in St. Louis between 1912 and 1933 were contrasted with similarly treated patients at the Barnes Hospital and the Ellis Fischel Cancer Hospital from 1940 to 1955. A poorer survival rate in the earlier series was related primarily to the greater frequency of advanced and larger tumors. That a significant reduction in breast cancer mortality can be achieved is becoming increasingly apparent. Among survey-detected breast cancers in the study conducted by the Health Insurance Plan of Greater New York, the 6-year mortality was half of that of controls. This reduction is even more impressive when one considers that among these patients were many with full invasive, mass-forming carcinomas at the time of initial screening. A recent report by Wanebo, Huvos and Urban discusses the treatment of prognostically favorable forms of breast cancer by modified radical mastectomy. It is possible to select from among their patients those who fit the definition of minimal breast cancer. In this group the 5-year survival rate was 97% and the 10-year survival rate was 95%. Only 1 patient died of breast cancer in 10 years. In another reported group of 65 patients with intraductal carcinoma only, there were no deaths due to breast cancer in 10 years. Should the NCI-ACS demonstration projects show, as now seems probable, that community screening programs can be effective in early breast cnacer detection, it is to be anticipated that widespread public demand for screening facilities will follow. This may present insurmountable logistic and economic problems. The total number of radiologists in the United States is not sufficient to screen annually the total population of women over age 40, or even over age 50. There is great need for the development of criteria for the ready identification of that segment of the population in which most of the cancers would be found...

Ultrasonographic features of hepatic adenomas in type I glycogen storage disease.

Focal hepatic masses were delineated by ultrasonography in three of five patients with type I glycogen storage disease (von Gierke's disease). Small hepatic adenomas were visualized as solitary or multiple hyperechoic solid lesions within enlarged, abnormally echogenic livers of increased attenuation. Larger adenomas were heterogeneous, with hypoechoic foci presumed to be secondary to necrosis, hemorrhage, or both. A previously unreported ultrasonographic finding is the markedly enhanced sound transmission identified deep to these solid tumors.

Early detection of chemotherapy-related pancreatic enlargement in children using abdominal sonography: a preliminary report.

At least two chemotherapeutic agents, prednisone and L-asparaginase, have been demonstrated to produce pancreatic injury. Early diagnosis of pancreatitis is frequently not possible, as symptoms are vague, physical findings may be minimal, and laboratory studies are frequently inconclusive until the injury is severe. Abdominal echography, as a monitor of pancreatic size, has proven to be helpful in the diagnosis of subclinical and early pancreatic injury of 14 of 19 selected children receiving prednisone and/or L-asparaginase therapy for acute leukemia or non-Hodgkin's lymphoma at the M.D. Anderson Hospital and Tumor Institute. Employment of this new diagnostic method permits prompt withdrawal of the causative agent(s), thus preventing further insult.

Ultrasound as an aid in the diagnosis and management of ovarian carcinoma: preliminary report.

Ultrasonic scanning was used to assist in the diagnosis and management of ovarian tumors. Tumor response to therapy was evaluated with sequential ultrasound examinations in conjunction with clinical observations. Contact B-mode scanning and physical examination were complementary in demonstrating a change in tumor size, delineating small amounts of ascites, and identifying early omental implants. The information was used to guide the patient's management by chemotherapy.

Squamous cell carcinoma of the renal pelvis: case report emphasizing sonographic and CT appearance.

The sonographic and CT appearance of squamous cell carcinoma of the renal pelvis is described. Clinical presentation, pathology, and radiologic diagnosis of this rare urothelial tumor are discussed. The sonographic or CT appearance may suggest this diagnosis preoperatively.

Dynamic incremental computed tomography in evaluation of the pulmonary hila.

Contrast-enhanced dynamic computed tomography (CT) with table incrementation between scans was used to evaluate the hila in 100 patients without hilar abnormality and 15 patients with hilar pathology. This method of hilar evaluation was found to be superior to conventional CT because hilar vascular structures could be clearly opacified. Opacification of normal hilar vessels permitted accurate detection of hypovascular hilar masses, some of which were very small, nonlobular, and invisible using conventional CT. The technique was also found to be useful in evaluating the hila in patients with pulmonary artery dilatation or pulmonary opacification contiguous with hilar borders. We recommend that contrast-enhanced dynamic incremental CT be used for hilar investigation in patients referred for hilar CT examination unless there is a specific contraindication to contrast medium administration.

MR appearance of the distended iliopsoas bursa.

The purpose of this essay is to illustrate the MR appearance of the distended iliopsoas bursa. The bursa must be recognized on MR scans to avoid confusing it with malignant neoplasms and other lesions.

The lumbosacral plexus: anatomic-radiologic-pathologic correlation using CT.

Before high resolution computed tomography (CT), the lumbosacral plexus was nearly impossible to image. While individual elements of the plexus are not consistently resolved using CT, the regional anatomy is reproducible and allows accurate evaluation. Normal regional anatomy was established by axial cadaver dissection and review of 233 normal computed tomographic examinations. This regional anatomy has been presented in detail. In addition, 17 patients with lumbosacral plexopathy due to benign, neoplastic and idiopathic causes were imaged. Our results show that CT is effective in the evaluation of suspected structural lesions of the lumbosacral plexus.

Stages I-III follicular lymphoma: role of CT of the abdomen and pelvis in follow-up studies.

PURPOSE: To evaluate the efficiency of axial computed tomography (CT) in detecting relapses of stage I, II, or III follicular lymphoma. MATERIALS AND METHODS: A total of 328 patients with previously untreated stage I, II, or III follicular lymphoma were treated between 1978 and 1994. Two hundred fifty-seven patients achieved complete response; 78 who relapsed form the basis of this study. Fifteen patients had stage I; 28, stage II; and 35, stage III disease. Fifteen patients underwent radiation therapy; 12, chemotherapy; and 51, radiation and chemotherapy. Medical records were reviewed to analyze the yield of abdominal and pelvic CT in detecting recurrence relative to the yield of standard clinical, hematologic, and imaging studies. A positive study was defined as one that led to or was abnormal at the diagnosis of recurrence. RESULTS: The median follow-up was 101 months. Eleven relapses were detected only at abdominal, pelvic, or both abdominal and pelvic CT. CONCLUSION: Fourteen percent (11 of 78) of the relapses were detected solely at abdominal and/or pelvic CT. Eleven (4.3%) of the 257 patients who achieved complete response benefited from abdominal and pelvic CT. The yield of the routine use of abdominal and pelvic CT in follow-up studies appears to be low for stages I-III follicular lymphoma.

Percutaneous fine needle aspiration biopsy of pancreatic and other abdominal masses.

Percutaneous fine needle aspiration biopsy of 18 patients with pancreatic masses, and 19 with other intra-abdominal tumors, showed it to be a safe, accurate procedure. A diagnostic biopsy yield was obtained in over 85% of the cases without clinical complications. Indications for fine needle biopsy are: (a) to avoid surgery by obtaining a histologic diagnosis; (b) to determine the staging of a neoplastic disease process; and (c) to facilitate treatment planning. The technique of "skinny needle" biopsy is discussed.

A comparison of radionuclide hepatobiliary imaging and real-time ultrasound for the detection of acute cholecystitis.

The relative value of hepatobiliary scintigraphy vs. real-time ultrasound for the identification of acute cholecystitis was evaluated. No significant difference in sensitivity (97% vs. 97%) existed between the two modalities. Scintigraphy demonstrated better specificity (93% vs. 64%) and predictive value (77% vs. 40%). Although real-time ultrasound provided improved sensitivity over static gray-scale imaging for identification of gallbladder disease, hepatobiliary scintigraphy remains the procedure of choice for acute cholecystitis detection.

Paclitaxel plus topotecan treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.

BACKGROUND: Used as single agents, paclitaxel and topotecan have demonstrated promising activity in treating patients with relapsed aggressive non-Hodgkin's lymphoma (NHL). We conducted a phase II clinical trial to investigate the activity and tolerability of the combination of both drugs. PATIENTS AND METHODS: Patients with refractory or relapsed aggressive NHL who had previously been treated with a maximum of two prior chemotherapeutic regimens were given intravenous infusions of paclitaxel 200 mg/m2 over three hours on day one and topotecan 1 mg/m2 over 30 minutes daily from days one to five. All patients received daily subcutaneous injections of filgrastim (granulocyte colony-stimulating factor) 5 microg/kg starting 24 hours after the last dose of chemotherapy until neutrophil recovery. Treatments were repeated every three weeks for a maximum of six courses. Patients who achieved partial remission or complete remission (CR) after at least two courses were offered stem cell transplantation, if eligible. RESULTS: Of the 71 patients eligible for this trial, 66 (93%) were evaluable for treatment response. The median age was 53 years (range 23 to 74 years). Thirty-six percent of the patients had previously been treated with ara-C/platinum-based regimens, and 48% failed to achieve CR after primary induction therapy. Sixty-seven percent of the patients had elevated lactate dehydrogenase levels at the time of treatment initiation. The overall response rate was 48% (95% confidence interval (95% CI): 36%-61%). Patients who had primary refractory disease had a response rate of 31%, compared with 65% for patients who did not. Similarly, the response rate of patients who failed to achieve CR after their most recent previous therapy was 37%, compared with a 65% response rate in patients who relapsed from a first or second CR. The median duration of response was six months. A total of 199 courses were given, with a median of three courses per patient. Neutropenia at levels < or = 500 leukocytes per microliter was observed after 32% of the courses, and thrombocytopenia at levels < or = 20,000 platelets per microliter was observed after 17% of the courses. Grade 3-4 neutropenic fever occurred after 6% of the courses. Non-hematologic toxic effects were predominantly grade 1-2. CONCLUSION: The combination of paclitaxel and topotecan is an effective first or second line salvage therapy for patients with relapsed or refractory aggressive NHL who had prior anthracycline- or platinum-based chemotherapy.