Unusual presentations of malignancy. Case 3. Mantle-cell lymphoma of soft tissue.
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Aged↗
Biomedical subjects
D C Fisher
Publications and source records attributed to D C Fisher.
CD6+ donor marrow T-cell depletion as the sole form of graft-versus-host disease prophylaxis in patients undergoing allogeneic bone marrow transplant from unrelated donors.
PURPOSE: The role of donor marrow T-cell depletion (TCD) in preventing graft-versus-host disease (GVHD) after transplantation of unrelated allogeneic marrow remains undefined. Because different TCD methodologies differ in the degree and specificity with which T cells are removed, it is likely that transplant outcomes would depend on which technique is used. Herein, we report results in the first 48 recipients of unrelated marrow using CD6+ TCD as the sole form of GVHD prophylaxis. PATIENTS AND METHODS: Median age of patients was 46 years (20 to 58 years). Donors were matched at A/B HLA loci. Ablation consisted of cyclophosphamide and fractionated total-body irradiation (TBI; 14 Gy). To facilitate engraftment, patients also received 7.5 Gy (22 patients) [corrected] or 4.5 Gy (26 patients) [corrected] of total lymphoid irradiation (TLI) before admission. No additional immune suppressive prophylaxis was administered. Granulocyte colony-stimulating factor was administered daily from day +1 to engraftment. RESULTS: All 48 patients demonstrated neutrophil engraftment. An absolute neutrophil count of 500 x 10(6)/L was achieved at a median of 12 days (range, 9 to 23 days). There were no cases of late graft failure. The number of CD34+ cells infused/kg was associated with speed of platelet and neutrophil recovery. The dose of TLI did not influence engraftment. Grades 2-4 acute GVHD occurred in 42% of patients (95% confidence interval [CI], 0.28 to 0.57). Mortality at day 100 was 19%. There have been only five relapses. Estimated 2-year survival was 44% (95% CI, 0.28 to 0.59) for the entire group, 58% for patients less than 50 years of age. In multivariable analysis, age less than 50 years (P =.002), cytomegalovirus seronegative status (P =.04), and early disease status at bone marrow transplant (P =.05) were associated with superior survival. CONCLUSION: CD6+ TCD does not impede engraftment of unrelated bone marrow after low-dose TLI, cyclophosphamide, and TBI. CD6+ TCD as the sole form of GVHD prophylaxis results in an incidence of GVHD that compares favorably with many adult studies of unrelated transplantation using unmanipulated marrow and immune-suppressive medications, especially in light of the median age of our patients (46 years). Although event-free survival in patients less than 50 years of age is very encouraging, older patients experience frequent transplantation-related complications despite TCD.
Adult↗
Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin's disease.
PURPOSE: To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin's disease. PATIENTS AND METHODS: Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin's disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had > or = 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. RESULTS: The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin's disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P =.04). Significant differences in FFTF were not seen by histology (P =.26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P =.25). CONCLUSION: Mantle irradiation alone in selected patients with early-stage Hodgkin's disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.
Adolescent↗
Recovery after stem-cell transplantation for hematologic diseases.
PURPOSE: Although the number of autologous and allogeneic stem-cell transplantations (SCT) is increasing, relatively little information about recovery after transplantation is available. Quantitative information appropriate for patient counseling is difficult to discern from the literature. We sought to suggest reasonable expectations for recovery and symptoms after SCT for hematologic malignancies and other disorders using the following measures: (1) objective measures of health status, such as frequency of clinic visits, need for rehospitalization, medication usage, work status, and overall and event-free survival; (2) qualitative assessment of quality of life, such as returning to a normal life, resumption of normal activities, satisfaction with appearance, and whether recovery has occurred; and (3) quantification of specific bothersome symptoms. PATIENTS AND METHODS: Autologous and allogeneic SCT recipients at a tertiary-care transplant center participated in the prospective, longitudinal questionnaire study. RESULTS: Three hundred twenty patients were studied. Questionnaire response rates at 6, 12, and 24 months range from 85% to 88% among survivors. Although autologous patients had better event-free and overall survival, fewer symptoms, and more complete recovery at 6 months, these advantages had largely equalized by 12 months. Specific bothersome symptoms were reported by less than 24% of patients after transplantation, except for fatigue and financial and sexual difficulties, which were more prevalent. CONCLUSION: These findings may help counsel patients considering transplantation and educate them about reasonable expectations for recovery. Overall, the low level of bothersome symptoms and continued recovery through the first year after transplantation are encouraging.
Activities of Daily Living↗
WAIS-III and WMS-III profiles of mildly to severely brain-injured patients.
Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-III (WMS-III; The Psychological Corporation, 1997) scores of patients with mild traumatic brain injury (MTBI, n = 23) to moderate-severe traumatic brain injury (M-S TBI, n = 22) were compared to those of 45 matched normal control patients. WAIS-III results revealed that IQ and index scores of MTBI patients did not significantly differ from those of controls, whereas M-S TBI patients received significantly lower mean scores on all measures. All M-S TBI patients' WMS-III index scores also revealed significantly lower scores in comparison to those of control participants, with the exception of Delayed Auditory Recognition. MTBI patients showed significantly lower mean index scores compared to normal controls on measures of immediate and delayed auditory memory, immediate memory, visual delayed memory, and general memory. Eta-squared analyses revealed that WMS-III visual indexes and WAIS-III processing speed showed particularly large effect sizes. These results suggest that symptomatic MTBI patients obtain some low WMS-III test scores comparable to those of more severely injured patients.
Adolescent↗
Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma.
We report the results of high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) in patients with relapsed indolent follicular lymphoma. Between March 1985 and May 1995, 153 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total body irradiation and bone marrow (BM) purging. All patients received multiple chemotherapy regimens before ABMT. At BM harvest, only 30% of patients were in complete remission, and overt BM infiltration was present in 47%. The disease-free survival (DFS) and overall survival (OS) are estimated to be 42% and 66% at 8 years, respectively. Patients whose BM was negative by polymerase chain reaction (PCR) for bcl2/IgH rearrangement after purging experienced longer freedom from recurrence than those whose BM remained PCR positive (P <.0001). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued complete remission (CR). The 12-year survival from diagnosis for these 153 patients is 69%. Considering that the median survival from diagnosis and first recurrence of patients with advanced follicular lymphoma are 8 and 5 years, respectively, our results provide evidence that myeloablative therapy and ABMT may prolong overall survival.
Adult↗
Reconstructing phylogeny with and without temporal data.
Conventional cladistic methods of inferring evolutionary relationships exclude temporal data from the initial search for optimal hypotheses, but stratocladistics includes such data. A comparison of the ability of these methods to recover known, simulated evolutionary histories given the same, evolved character data shows that stratocladistics recovers the true phylogeny in over twice as many cases as cladistics (42 versus 18 percent). The comparison involved 550 unique taxon-by-character matrices, representing 15 evolutionary models and fossil records ranging from 100 to 10 percent complete.
Biological Evolution↗
Autologous bone marrow transplantation after histologic transformation of indolent B cell malignancies.
The role of high-dose therapy and autologous stem cell transplantation in diffuse large B cell lymphoma (DLBCL) after transformation is controversial. We have retrospectively analyzed patients with chemosensitive disease and a history of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma who underwent high-dose chemoradiotherapy and bone marrow transplantation (BMT) with anti-B cell monoclonal antibody-purged autologous marrow for DLBCL. Between December 1982 and August 1997, 27 patients underwent autologous BMT using a uniform ablative regimen with cyclophosphamide, total-body irradiation, and bone marrow purging. All patients received multiple chemotherapy regimens before autologous BMT. At bone marrow (BM) harvest, only 44% of patients were in complete remission, and overt BM infiltration was present in 37%. After cyclophosphamide and total-body irradiation, no treatment-related deaths were seen. Eleven of the 27 patients relapsed, and four patients developed myelodysplasia/acute myelogenous leukemia. In seven patients in whom pathologic studies were available after relapse, the histology remained DLBCL. Twelve patients remained alive and in complete remission with a median follow-up of 36 months (range 10-132). The disease-free survival and overall survival are estimated to be 46% (90% confidence interval 28-64) and 58% (40-76) at 5 years, respectively. Patients whose disease underwent histologic transformation within 18 months of their initial diagnosis of indolent lymphoma had significantly better overall survival. Selected patients with histologic transformation, particularly those whose transformation occurs early in the course of their disease and who remain chemosensitive, may experience prolonged survival after autoBMT.
Adult↗
Large gradient across a partially ligated left atrial appendage.
The left atrial appendage is frequently ligated during mitral valve surgery to decrease the future risk of embolic events. The postoperative detection of a partially occluded left atrial appendage has previously been reported with the use of transesophageal echocardiography. We describe an unusual case in which Doppler echocardiography demonstrated a remarkably high-velocity jet emanating from a partially ligated left atrial appendage.
Echocardiography, Transesophageal↗
Reduced mortality following bone marrow transplantation for breast cancer with the addition of peripheral blood progenitor cells is due to a marked reduction in veno-occlusive disease of the liver.
Clinical trials involving breast cancer in the Duke University Bone Marrow Transplant Program were evaluated to assess the association between type of hematopoietic support and treatment-related morbidity/mortality. Case histories of patients treated with high-dose chemotherapy and hematopoietic rescue on three separate protocols between 1986 and 1994 were reviewed. This included 307 patients with stage IV disease and 85 patients with high-risk (10 or more positive axillary lymph nodes) stage II or III disease. One hundred and twenty-eight of these patients were rescued with autologous bone marrow (BM) alone and 264 additionally received autologous peripheral blood progenitor cells (PBPC). The 100 day transplant-related mortality rate in those patients who received BM alone was 20.3%, with an overall mortality rate due to the high-dose chemotherapy procedure of 24.2%. The PBPC-treated group experienced a 100 day transplant-related mortality of only 6.1% and an overall trans-plant- related mortality of 10.2%. Sixteen of 31 deaths were attributed to veno-occlusive disease (VOD) in the group that received BM alone compared to only one VOD-related death in the PBPC group. These data demonstrate a marked improvement in transplant-related mortality which is related to the use of PBPC. This effect has been almost entirely due to a reduction in mortality from hepatic veno-occlusive disease.
Adult↗
CD6+ T cell-depleted allogeneic bone marrow transplantation for non-Hodgkin's lymphoma.
For patients with non-Hodgkin's lymphoma (NHL) undergoing blood or bone marrow transplantation (BMT), the use of autologous grafts has often been preferred to that of allogeneic stem cells because of a significantly lower incidence of non-relapse mortality. If complications associated with allo-BMT could be minimized without compromising efficacy, then it might become a preferred strategy for certain subsets of patients. In this report, we describe the toxicity and long-term efficacy of T cell-depleted allogeneic BMT using anti-CD6 monoclonal antibody and complement alone to reduce the risk of GVHD and its sequelae. Twenty-two patients, aged 18-60 years, with high (n = 10), intermediate (n = 9), or low (n = 3) grade NHL underwent HLA-identical allogeneic BMT from siblings. Patients had either relapsed after at least one remission or never achieved a full remission with chemotherapy. Twenty patients had a history of marrow involvement. Bone marrow was depleted of CD6+ T cells with T12 monoclonal antibody and complement as the sole form of GVHD prophylaxis. Stable hematopoietic engraftment occurred in all 22 patients. Four patients developed grade 2 and 1 patient grade 3 GVHD (23% grades 2-4 GVHD). Chronic GVHD has occurred in three patients. Treatment-related mortality was very low. Only one patient died while in remission. Thirteen patients are alive and free of disease with a median follow-up of 30 months. Estimated event-free and overall survivals are 54 and 59%, respectively. CD6 allogeneic marrow transplantation is associated with a low risk of transplant-related complications and may offer advantages for certain patients with recurrent NHL felt to be at high risk for relapse after autologous transplantation.
Adolescent↗
Identification of bacterial isolates obtained from intestinal contents associated with 12,000-year-old mastodon remains.
Mastodon (Mammut americanum) remains unearthed during excavation of ancient sediments usually consist only of skeletal material, due to postmortem decomposition of soft tissues by microorganisms. Two recent excavations of skeletal remains in anoxic sediments in Ohio and Michigan, however, have uncovered organic masses which appear to be remnants of the small and large intestines, respectively. Macrobotanical examinations of the composition of these masses revealed assemblages of plant material radiocarbon dated to approximately 11,500 years before the present and thought to be incompletely digested food remains from this extinct mammal. We attempted to cultivate and identify bacteria from the intestinal contents, bone-associated sediments, and sediments not in proximity to the remains using a variety of general and selective media. In all, 295 isolates were cultivated, and 38 individual taxa were identified by fatty acid-methyl ester (FAME) profiles and biochemical characteristics (API-20E). The taxonomic positions of selected enteric and obligately anaerobic bacteria were confirmed by 16S ribosomal DNA (rDNA) sequencing. Results indicate that the intestinal and bone-associated samples contained the greatest diversity of bacterial taxa and that members of the family Enterobacteriaceae represented 41% of all isolates and were predominant in the intestinal masses and sediments in proximity to the skeleton but were uncommon in the background sediments. Enterobacter cloacae was the most commonly identified isolate, and partial rDNA sequencing revealed that Rahnella aquatilis was the correct identity of strains suggested by FAME profiles to be Yersinia enterocolitica. No Bacteroides spp. or expected intestinal anaerobes were recovered. The only obligate anaerobes recovered were clostridia, and these were not recovered from the small intestinal masses. Microbiological evidence from this study supports other, macrobotanical data indicating the intestinal origin of these masses. Whether these organisms are direct descendants of the original intestinal microbiota, however, cannot be established.
Animals↗
High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission.
PURPOSE: The role for high-dose therapy and autologous stem-cell transplantation in mantle-cell lymphoma (MCL) is unknown. We retrospectively analyzed patients with chemosensitive disease who underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) for MCL in first remission, as well as following relapse from conventional therapy. PATIENTS AND METHODS: Between August 1985 and April 1996, 28 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total-body irradiation (TBI) and a bone marrow-purging regimen. Re-review of original tissue demonstrated that all patients had morphologic, phenotypic, and genotypic characteristics of MCL. MCL was the original diagnosis in 21 patients, whereas seven patients had a prior diagnosis of diffuse small cleaved-cell lymphoma. RESULTS: Twenty patients received multiple regimens before ABMT, while eight underwent ABMT in first complete remission (CR)/partial remission (PR) following CHOP induction. At bone marrow harvest, only 18% of patients were in CR and overt BM infiltration was present in 57%. Following cyclophosphamide/TBI, no treatment-related deaths were seen. Nineteen of 28 patients have relapsed at a median time of 21 months (range, 3 to 70). Of eight patients transplanted in first CR/PR, five have relapsed. Nine patients are in continuous CR with a median follow-up time of 24 months (range, 10 to 135). Disease-free survival (DFS) and overall survival (OS) are estimated to be 31% and 62% at 4 years, respectively. CONCLUSION: ABMT using cyclophosphamide/TBI conditioning may at best be effective in only a small fraction of patients with relapsed MCL. The lack of plateau with a median follow-up time of 24 months suggests cure may not be achievable. The role of this therapy in patients in first remission requires more study using better induction therapy to enhance the CR rate before ABMT.
Adult↗
Cladistic analysis and anthropoid origins.
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Animals↗
Cyclophosphamide, doxorubicin, vincristine, prednisone dose intensification with granulocyte colony-stimulating factor markedly depletes stem cell reserve for autologous bone marrow transplantation.
Hematopoietic growth factors allow dose escalation of chemotherapy. This approach may potentially reduce the quality and quantity of hematopoietic stem cells. The capacity of stem cells recovered after dose intensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hematopoietic engraftment was compared in two sequential trials of induction therapy (standard dose cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] without growth factors or dose intensification CHOP supported by granulocyte colony-stimulating factor [G-CSF ]) followed by identical myeloablative therapy and autologous stem cell support. Neutrophil, platelet, and red blood cell (RBC) engraftment were compared on days 100, 180, and 360 after stem cell reinfusion. Despite similar patient characteristics including reinfusion of comparable numbers of marrow mononuclear cells, after stem cell transplantation, a highly significant prolongation of neutrophil and platelet engraftment was seen in patients who received high dose CHOP and G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemotherapy and G-CSF recruited stem cells into a proliferative phase and that G-CSF allowed retreatment at a time when stem cells were susceptible to damage by cytotoxic therapy. Such inadequate hematologic engraftment after myeloablative therapy might be avoided by either shortening the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additional stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be used with caution if stem cells are to be used to support myeloablative therapy.
Adult↗
Thrombotic microangiopathy as a complication of high-dose chemotherapy for breast cancer.
Five hundred and eighty-one patients with stage II-IV breast cancer were treated at Duke University Medical Center with high-dose chemotherapy, followed by hematopoietic support. All patients received a conditioning regimen of cyclophosphamide, cisplatin and carmustine. Of these patients, 15 (2.6%) developed symptoms similar to the hemolytic-uremic syndrome with evidence of thrombotic microangiopathy (TMA). The time of onset ranged from 75 days to 281 days post-transplant, with a median of 143 days. Hemolytic anemia and thrombocytopenia, without alternative cause, were required for diagnosis. All patients were treated with steroid therapy. In addition, 12 patients were treated primarily with plasmapheresis, and received a median of 46 treatments. Additional therapy included staphylococcal protein A column apheresis (eight patients), vincristine (three patients) and danazol (one patient). The mortality rate was 11 of 15 patients (73%). These patients had a median survival of 41 days from diagnosis of TMA (range 2-76 days). The four survivors are alive at 76, 186, 1837 and 2387 days from diagnosis of TMA. Three of these patients received twice daily plasmapheresis and protein A column apheresis therapy. One patient recovered without specific therapy. TMA is an infrequent complication of high-dose chemotherapy, but is associated with a high mortality. It frequently follows significant pulmonary drug toxicity. Survival may be improved with early diagnosis and aggressive plasmapheresis therapy.
Anemia, Hemolytic↗
Central nervous system lymphoma not detectable on single-photon emission CT with thallium 201.
A 33-year-old man with acquired immunodeficiency syndrome had an erosive supraglottic mass visible on CT scans of the neck; biopsy was postponed because of the patient's debilitated condition. Two weeks later, he was admitted with altered mental status; an MR image of the brain obtained at that time showed multiple bilateral mass lesions, the largest of which was 5 cm. Findings on a thallium-201 single-photon emission CT (SPECT) scan of the brain were normal. Ten days later, the patient died and autopsy showed both the neck and the brain lesions to be large-cell lymphoma. This case is counterevidence to the reported 100% sensitivity of thallium-201 brain SPECT for demonstrating lymphoma of the central nervous system.
Adult↗
The incidence of patent foramen ovale in 1,000 consecutive patients. A contrast transesophageal echocardiography study.
STUDY OBJECTIVE: Patent foramen ovale (PFO) is present in 10 to 35% of people and has been reported to be an important risk factor for cardioembolic cerebrovascular accidents (CVAs) and transient ischemic attacks (TIAs), especially in younger patients. While contrast transthoracic echocardiography has been used to detect PFO, contrast transesophageal echocardiography (TEE) has a greater sensitivity. Prior studies reported the incidence of PFO in patients presenting with a CVA or TIA. DESIGN: To determine the incidence of PFO in a more general population, we reviewed 1,000 consecutive TEEs performed with contrast and color Doppler for the presence of PFO and other cardioembolic risk factors, including atrial septal aneurysm (ASA), aortic plaque, atrial fibrillation (AFib), and atrial thrombi. While imaging with monoplane or biplane TEE, multiple injections of agitated saline solution were injected during cough or Valsalva maneuver to detect flow through a PFO. PATIENTS: There were 482 male and 518 female patients with mean age of 60 +/- 17 years (range 11 to 93 years). RESULTS: Patent foramen ovale was found in 9.2% of all patients and, though seen in all age groups divided by decade, the incidence in patients aged 40 to 49 years was greater than those aged 70 to 79 years (12.96% vs 6.15%, p = 0.03). Contrast TEE had a much higher detection rate than color Doppler alone. Importantly, there was no greater incidence of PFO in patients with CVA vs those without CVA, or in male vs female patients. Also, there was a very strong correlation between the presence of ASA and PFO (p < .001). CONCLUSION: Thus, PFO detected by TEE, frequently seen with ASA, is seen in all age groups and does not in itself present a risk factor for CVA. The association of PFO with peripheral thrombosis and CVA needs further study.
Adolescent↗