Biomedical subjects

Peter McLaughlin

Publications and source records attributed to Peter McLaughlin.

At least 37 records · Page 2Linked to original sources

PubMed2004

Follicular lymphoma international prognostic index.

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs < or = 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs > or = 120 g/L), number of nodal areas (> 4 vs < or = 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk (> or = 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.

Adult↗

PubMed2004

Thalidomide for patients with recurrent lymphoma.

BACKGROUND: Thalidomide has significant clinical activity in patients with multiple myeloma. However, its activity against other lymphoid tumors is unknown. The authors reported their experience with thalidomide in patients with recurrent/refractory non-Hodgkin lymphoma and in patients with Hodgkin disease. METHODS: Nineteen patients (median age, 62 years) who had undergone a median of 5 previous treatment regimens were treated with escalating doses of thalidomide (200-800 mg per day) until disease progression or prohibitive toxicity was observed. The authors measured serum levels of angiogenesis factors before and after treatment. RESULTS: One patient (5%) with evidence of recurrent gastric mucosa-associated lymphoid tissue lymphoma achieved a complete response, and 3 patients (16%) achieved stable disease. CONCLUSIONS: The current study suggests that thalidomide has limited single-agent activity in heavily pretreated patients with recurrent or refractory lymphoma.

Adult↗

PubMed2004

Radiolabeled antibody therapy in non-Hodgkins lymphoma: radiation protection, isotope comparisons and quality of life issues.

Anti-CD20 antibodies radiolabeled with I-131 tositumomab (Bexxar) or Y-90-Ibritumomab tiuxetan (Zevalin), are similarly efficacious in treating chemotherapy-refractory non-Hodgkin's lymphoma. The relative merits of both radioimmunoconjugates with respect to practical issues, including radiation exposure risk, the advantages and disadvantages of the respective isotopes and other parameters that could affect a patient's quality of life are also important. I-131-labeled antibody treatment often requires inpatient hospitalization due to the inherent risk of exposure from gamma emissions, and patients and families should follow detailed instructions to prevent undue exposure. Other issues relevant to patients and medical staff include: (1) the need for dosimetry to calculate effective therapeutic doses of I-131-labeled anti-B1 (Bexxar) compared with the lack of correlation of dosimetry with marrow toxicity for IDEC-Y2B8 (Zevalin), (2) determining the acute and long-term toxic effects of each agent, (3) time commitments for nuclear medicine staff and patients along with the relative ease of administration, and (4) cost considerations. A more challenging future issue will be to determine the optimal use of Bexxar and Zevalin alone and in combination in ways that will significantly affect patient outcome without compromising quality of life. The recent demonstration of significant response rates in patients having chemotherapy-refractory Non-Hodgkin's Lymphoma (NHL) using both on I-131- and Y-90-labeled anti-CD20 antibodies with minimal toxicity has stimulated comparison of I-131 tositumomab (Bexxar) and Ibritumomab tiuxetan (Zevalin) in terms of radiation safety requirements, the advantages and disadvantages of both radionuclides, and quality-of-life (QOL) issues. Therefore, in this review, we attempt to compare the relative merits of (Bexxar and Zevalin) and address important practical considerations that may influence patient and physician choices regarding treatment using these agents.

Antibodies, Monoclonal↗

PubMed2003

Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma.

PURPOSE: Patients with relapsed mantle-cell lymphoma have poor prognosis and short survival. Our aim was to determine the efficacy of nonablative allogeneic stem-cell transplantation in patients with relapsed mantle-cell lymphoma. PATIENTS AND METHODS: Eighteen patients were treated in one of two consecutive trials. Thirteen patients underwent a conditioning regimen of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days), and high-dose rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m2 daily for 4 days), fludarabine (30 mg/m2 daily for 2 days), and cytarabine (1,000 mg/m2 daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. RESULTS: The median age was 56.5 years. Patients underwent a median of three prior chemotherapy regimens. Prior autologous transplantation failed in five (28%) patients and 16 (89%) had chemosensitive disease. Donor cell engraftment occurred in all patients. Eight patients (44%) required no platelet or RBC transfusion, and acute graft-versus-host disease of greater than grade 2 did not develop in any patient. The day-100 mortality was 0%. Complete remission (CR) occurred in 17 patients. Three patients progressed, and one was reinduced into continuous CR with donor lymphocyte infusion. With a median follow-up period of 26 months, the actuarial probability of current-event-free-survival at 3 years was 82% (95% CI, 65% to 99%). CONCLUSION: Our data suggest that nonablative allogeneic transplantation is a safe and potentially effective strategy for patients with relapsed and chemosensitive mantle-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Stage III follicular lymphoma: long-term follow-up and patterns of failure.

PURPOSE: To analyze the long-term outcomes and pattern of failures for Stage III follicular lymphomas. METHODS AND MATERIALS: A retrospective review of all patients with Stage III follicular lymphoma presented to our institution between 1978 and 1993 was performed. One hundred ten patients were eligible and form the basis of this analysis. Fifty-seven patients were male. The median age was 57 years (range: 21-82 years). The treatments were as follows: chemotherapy alone (CTX), 39 patients; combined modality with chemotherapy and radiation therapy (CMT), 69; radiation therapy alone, 2. Radiation therapy fields were as follows: regional, 13 patients; extended, 6; subtotal, 44; and central lymphatic, 8. The median number of chemotherapy cycles was 8, and 98 patients received doxorubicin-containing regimens. Enough information was available to calculate the International Prognostic Index for 107 patients. The following prognostic factors were examined for predictive value in overall survival (OS) and freedom from progression (FFP) by univariate and multivariate analyses: International Prognostic Index, gender, lactate dehydrogenase (LDH) (normal vs. elevated), B symptoms, performance status, beta-2 microglobulin, presence or absence of a bulky disease, age (</= vs. >60 years), number of sites of involvement, treatment (CTX vs. CMT), and pathology. To minimize patient selection biases given the nature of the retrospective analysis, the patterns of relapse were analyzed only for the patients who achieved a complete response. RESULTS: The median follow-up for the alive patients was 9.5 years (range: 1.1-19.5 years). Complete response was achieved in 80 patients: 24 of 39 patients in the CTX group (62%), 54 of 69 patients in the CMT group (78%), and 2 of 2 patients in the radiation therapy alone group. The actuarial 5- and 10-year OS rates were 65% and 42%, respectively. The 5- and 10-year FFP was 42% and 26%, respectively. Significant prognostic factors by multivariate analyses were age and LDH for OS and LDH for FFP. For complete responders, 5-year freedom from recurrence in the original sites of involvement (with or without recurrence in the new sites) was 43% for CTX and 60% for CMT patients (p = 0.03, Wilcoxon). Five-year freedom from isolated recurrence in the original sites of involvement was 60% for CTX and 69% for CMT patients (p = 0.17). The 5-year overall FFP was 43% for CTX patients and 56% for CMT patients (p = 0.06). CONCLUSION: Combined modality treatment seems to give an advantage in terms of disease control in the primary sites compared to chemotherapy alone, though the advantages in OS and FFP were not statistically significant in our patient population. By multivariate analyses, LDH was a significant prognostic indicator for OS and FFP, whereas age was for OS.

Adult↗

PubMed2003

Central lymphatic irradiation for stage I-III follicular lymphoma: report from a single-institutional prospective study.

PURPOSE: This study was undertaken to update our experience with follicular lymphoma treated with central lymphatic irradiation (CLI). METHODS AND MATERIALS: A total of 47 patients were treated with CLI between January 1993 and March 2000 in a prospective manner. CLI consisted of mantle, whole abdomen, and pelvic radiation fields with a 1-month break after each field. Each field was treated to 3000-3060 cGy at 150-180 cGy per fraction followed by a boost dose of 900 cGy to the areas with gross disease. The median age was 52 years (range: 29-73 years). There were 29 males. The diagnoses were as follows: follicular small cleaved-cell lymphoma, 23 patients; follicular mixed-cell lymphoma, 19 patients; follicular large-cell lymphoma, 5 patients. Ann Arbor stages were as follows: I, 5 patients; II, 14 patients; and III, 28 patients. The International Prognostic Index (IPI) categories were as follows: 0, 14 patients; 1, 24 patients; and 2, 9 patients. M. D. Anderson Tumor Score was as follows: 0, 14 patients; 1, 18 patients; 2, 9 patients; 3, 4 patients; 4, 1 patient; and unknown, 1 patient. Two patients had abnormal LDH levels, and 11 patients had beta2M levels >2 mg/dL. Gender, pathology, stage, IPI, Anderson Tumor Score, beta2M, and number of disease sites were examined for significance in freedom from progression (FFP) by univariate analyses. RESULTS: The median follow-up was 54 months (range: 8-93 months) for the 45 surviving patients. Every patient achieved a complete response, except for 1 patient whose lymphoma progressed to diffuse large-cell lymphoma during treatment. The 5-year overall survival and FFP were 94% and 53%, respectively. No failure has yet been observed beyond 55 months of follow-up with 13 patients at risk. Patterns of failure were as follows: within the radiation field, 10; outside the fields, 4; and both, 2. Of the seven variables investigated, beta2M >2 mg/dL and IPI >1 were the only significant adverse prognostic factors for FFP (p = 0.023 and 0.046, respectively). CONCLUSIONS: CLI is well tolerated and seems to achieve durable FFP in about half of the patients with Stage I-III follicular lymphoma. Most of the experiences with CLI come from the treatment of Stage III disease and are very similar to our previous experience with combined modality treatment. Whether a plateau in FFP can be maintained beyond 5 years remains to be seen.

Adult↗

PubMed2003

Primary central nervous system lymphoma: Phase I evaluation of infusional bromodeoxyuridine with whole brain accelerated fractionation radiation therapy after chemotherapy.

BACKGROUND: The current study was performed to determine the maximum tolerated dose (MTD), toxicity, and outcome of infusional 5 bromo-2'-deoxyuridine (bromodeoxyuridine; BUdR) given with accelerated fractionation whole brain radiation therapy (WBRT) after chemotherapy for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: Twelve patients with untreated and histologically confirmed PCNSL were entered on the study between 1994 and 1996. Chemotherapy was comprised of one course of IDHAP plus high-dose methotrexate (HD-MTX). IDHAP is comprised of idarubicin at a dose of 1.5 mg/m(2)/day x 4 days intravenously by continuous infusion (i.v. CI), dexamethasone at a dose of 40 mg i.v. on Days 1-5, cytosine arabinoside at a dose of 2000 mg/ m(2) i.v. on Day 5 after cisplatin, and cisplatin at a dose of 25 mg/m(2)/day x 4 days i.v. CI. HD-MTX was given at a dose of 3.5 g/m(2) i.v. between Day 10 and Day 14 after IDHAP. BUdR was given as an i.v. CI over 48 hours, 2-3 days prior to WBRT and then weekly during WBRT. Dose escalation started at 1.5 g/m(2)/day for Cohort 1 with subsequent increments of 0.3 g/m(2)/day. The WBRT dose was 45 grays (Gy) at a dose of 1.5 Gy twice a day, 5 days per week. Neurocognitive testing was performed before, during, and after treatment. RESULTS: Nine of 12 patients entered on the study received BUdR. One of 3 patients in Cohort 1 developed leukoencephalopathy (LEP), a dose-limiting toxicity (DLT), within 2 months of the completion of therapy. Therefore, the next cohort received the same dose level. Because no toxicity was observed in Cohort 2, the third cohort received a BUdR dose of 1.8 g /m(2)/day. Shortly after completing enrollment in Cohort 3, 3 more patients developed LEP, including 2 from Cohort 1 who had received a dose of 1.5 g/m(2)/day. Thus, DLT occurred at a dose of 1.5 g/m(2)/day, the starting level in the current study. As a result, the trial was stopped. Eight of 12 patients achieved a complete response, 3 achieved a partial response, and 1 patient died before response assessment. CONCLUSIONS: Hyperfractionated WBRT with concurrent BUdR after chemotherapy was found to result in modest disease control but has unacceptable neurotoxicity.

Adult↗

PubMed2003

A pilot study of rituximab in patients with recurrent, classic Hodgkin disease.

BACKGROUND: To explore the potential role of infiltrating benign B cells in classic Hodgkin disease (HD) lesions in supporting the survival of malignant Hodgkin and Reed-Sternberg (H/RS) cells, the authors initiated a pilot study of rituximab. Rituximab is used to primarily deplete normal B cells from HD lesions. METHODS: Patients with recurrent, classic HD who had received a minimum of two prior treatment regimens, regardless of whether H/RS cells expressed CD20, were treated with 6 weekly doses of 375 mg/m2 rituximab to selectively deplete infiltrating benign B cells. Objective tumor response was determined 3 weeks after completion of the last dose of rituximab and every 3 months thereafter. Serum samples were collected from patients before they started rituximab therapy and 3 weeks after the final course of rituximab. Serum cytokine levels of interleukin 6 (IL-6), IL-10, IL-12, IL-13, and interferon gamma were determined using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Twenty-two patients with nodular sclerosis histology were evaluable for treatment response. Five patients (22%) achieved partial or complete remission that lasted for a median of 7.8 months (range, 3.3-14.9 months). Remissions were observed in patients only at lymph node and splenic sites, but not at extranodal sites, and were irrespective of CD20 expression by H/RS cells. Furthermore, systemic (B) symptoms resolved in six of seven patients after therapy. In two patients, partial remissions were associated with a decline in serum IL-6 levels. CONCLUSIONS: The current data suggest that rituximab therapy in patients with recurrent, classic HD can alter serum IL-6 cytokine levels, can improve B symptoms, and may result in clinical remissions.

Adolescent↗

PubMed2003

A zero PSA slope in posttreatment prostate-specific antigen supports cure of patients with long-term follow-up after external beam radiotherapy for localized prostate cancer.

PURPOSE: To determine whether the rate of change in prostate-specific antigen (PSA) in patients treated with external beam radiotherapy for localized prostate cancer improves our ability to define which patients are likely to be cured of their disease. METHODS AND MATERIALS: Patients treated between 1987 and 1995 at the University of California, San Francisco and the University of Michigan for localized prostate cancer with external beam radiotherapy and without hormonal ablation were evaluated for this study. The PSA slope was calculated for 199 patients who were disease free by the American Society for Therapeutic Radiology and Oncology consensus definition for at least 4 years and at last follow-up. Patients were categorized into groups defined by no increase, minimal increase, modest increase, and a definite increase in change in PSA level, corresponding to slopes of 0.0-0.1, >0.1-0.5, and >0.5 ng/mL/y, respectively. RESULTS: Fifty-four percent of the patients displayed a non-increasing PSA (Group 1), 23% had a minimal increase (Group 2), 17% had a modest increase (Group 3), and 6% had a definite increase (Group 4). Patients with a non-increasing PSA slope had a significantly longer time to nadir (median 47.8, 31.6, 29.9, and 23.3 months for Groups 1-4, respectively, p = 0.0001) and a lower median PSA nadir (median 0.30, 0.40, 0.55, and 1.00 ng/mL for Groups 1-4, respectively, p = 0.0006). CONCLUSION: On the basis of PSA kinetics, we believe that a group of patients can be defined who appear to be cured of localized prostate cancer (i.e., have a zero slope). These patients have a lower and later PSA nadir, as well as a more substantial proportional effect of external beam radiotherapy on their PSA level. Patients with a definite increase in PSA slope are erroneously labeled disease free by the American Society for Therapeutic Radiology and Oncology consensus definition.

Aged↗

PubMed2003

Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma.

PURPOSE: Standard therapy for patients with stage I-II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients. PATIENTS AND METHODS: A total of 102 eligible patients with stage I-II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT. RESULTS: The patients' median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (>/= 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P =.02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P <.0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields. CONCLUSION: With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.

Adult↗

PubMed2003

Phase I clinical and pharmacology study of clofarabine in patients with solid and hematologic cancers.

PURPOSE: To define the maximum-tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of clofarabine, given as a 1-hour infusion daily for 5 days, in patients with solid tumors and with acute leukemia. PATIENTS AND METHODS: The initial part of the study defined the MTD and DLT in solid tumors. The second part of the study defined the MTD and DLT in acute leukemia. RESULTS: The starting dose of clofarabine (15 mg/m(2)) was myelosuppressive, requiring several dose de-escalations to 2 mg/m(2), the dose suggested for phase II studies in solid tumors. Dose escalation in acute leukemia started at 7.5 mg/m(2), with several escalations to 55 mg/m(2). The DLT was reversible hepatotoxicity at 55 mg/m(2). The recommended dose for acute leukemia phase II studies was 40 mg/m(2). Among 32 treated patients with acute leukemia, two achieved a complete response and three had a marrow complete response without platelet recovery (hematologic improvement), for an overall response rate of 16%. At 40 mg/m(2), the median plasma clofarabine level was 1.5 micro mol/L (range, 0.42 to 3.2 micro mol/L; n = 7). Cellular and plasma pharmacokinetic studies suggested dose proportionality but showed a wide variation in intracellular concentrations of clofarabine triphosphate. CONCLUSION: This phase I study defined the following two MTDs for clofarabine given as a 1-hour infusion daily for 5 days: 2 mg/m(2) for solid tumors, the DLT being myelosuppression; and 40 mg/m(2) for acute leukemia, the DLT being hepatotoxicity. Encouraging activity was observed in acute leukemia.

Adenine Nucleotides↗

PubMed2003

Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma.

BACKGROUND: The reported frequency of gastrointestinal (GI) tract involvement in patients with mantle cell lymphoma (MCL) is 15-30%. However, this figure most likely is an underestimate because most patients with MCL involving the GI tract previously reported were examined endoscopically only if they had GI tract symptoms. The impact of endoscopic assessment on the management of MCL patients is unknown. METHODS: From March 1998 to May 2001 baseline upper and lower endoscopy of the GI tract was performed in consecutive untreated patients with MCL as part of a prospective therapeutic trial. Biopsies were performed on abnormal as well as macroscopically normal mucosa. Endoscopy was repeated during treatment and as part of follow-up evaluations. RESULTS: Only 26% of patients presented with GI symptoms at the time of diagnosis. MCL was present histologically in the lower GI tract of 53 of 60 patient (88%) and in the upper GI tract of 28 of 58 patients (43%). Microscopic evidence of MCL was found in 84% of patients with normal visual (macroscopic) findings by lower endoscopy and in 45% of patients with macroscopically normal findings by upper endoscopy. Despite this high frequency of GI tract involvement, the use of upper and lower endoscopy with biopsies in this group of patients resulted in changes in clinical management in only three (4%) patients. CONCLUSIONS: Gastrointestinal tract involvement was found to be present in most patients with MCL, usually at a microscopic level involving macroscopically normal mucosa. The use of aggressive staging evaluation of the GI tract was found to have little impact on patient management decisions in the current study.

Adult↗

PubMed2002

Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma.

Treatment for patients with stage IV indolent lymphoma ranges from watchful waiting to intensive chemotherapy and stem cell transplantation. In this trial we compared 2 induction regimens followed by 1 year of interferon maintenance therapy. Fludarabine, mitoxantrone (Novantrone), and dexamethasone (FND) were compared with an alternating triple therapy (ATT) regimen (CHOD-Bleo, ESHAP, and NOPP). Maintenance interferon/dexamethasone was given for 1 year in both treatment arms. Endpoints were comparisons of remission rates, survival, failure-free survival (FFS), molecular response rates, and toxicities. One hundred forty-two patients with previously untreated stage IV indolent lymphoma were evaluable (73 on FND; 69 on ATT). The overall response rates were 97% for FND and 97% for ATT (P =.9). The median follow-up is 5.9 years. The 5-year survival rates were 84% with FND and 82% with ATT (P =.9); the 5-year FFS rates were 41% with FND and 50% with ATT (P =.02). In a multivariate analysis, factors predicting for longer FFS were beta(2)-microglobulin less than 3 mg/L (P =.01) and ATT treatment (P =.03). ATT was associated with a substantially higher rate of grade 3-4 toxicities than FND. In conclusion, both regimens were associated with high rates of response and survival. ATT was associated with substantially longer FFS, but it was more toxic than FND.

Adult↗

PubMed2002

CD20 expression in Hodgkin and Reed-Sternberg cells of classical Hodgkin's disease: associations with presenting features and clinical outcome.

PURPOSE: CD20 can be expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's disease (HD), but its clinical significance remains controversial. Therefore, we correlated CD20 expression with presenting features and clinical outcome of untreated patients with classical HD. PATIENTS AND METHODS: Patients were eligible if they were previously untreated and human immunodeficiency virus-1 negative, had biopsy-proven classical HD, and if pretreatment paraffin-embedded tumor tissue was available. CD20 expression was determined by immunohistochemistry without knowledge of clinical outcome. A tumor was considered positive if any HRS cells expressed CD20, but other cutoffs for number of CD20-positive HRS were also investigated. RESULTS: We identified 598 patients whose median age was 30 years and of whom 55% were male. HRS cells expressed CD20 in 132 (22%) of 598 patients with classical HD. When any percentage of CD20 expression in HRS cells was used as a cutoff, the 5-year failure-free survival (FFS) for positive versus negative tumors was 86% versus 84%, respectively, for 302 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens (P =.7 by log-rank test), 74% versus 77%, respectively, for 181 patients treated with mitoxantrone, vincristine, vinblastine, and prednisone and radiotherapy (P =.7 by log-rank test), 74% versus 84%, respectively, for 54 patients treated with MOPP (P =.4 by log-rank test), and 77% versus 88% for 53 patients treated only with radiotherapy (P =.5 by log-rank test). The 5-year FFS was not statistically different when cutoffs of 5% up to 50% for CD20-positive HRS cells were used. CONCLUSION: CD20 is expressed by HRS cells in 22% of patients with classical HD but is not associated with different FFS after treatment with equivalent regimens.

Adolescent↗

PubMed2002

How congenital heart disease originates in fetal life.

Knowledge of the early development of the heart has increased rapidly in recent years as microscopic techniques, experimental models using animal, avian and insect species, and various genetic techniques have been brought to bear on the mysteries of human fetal cardiac development. The development of the heart occurs rapidly from embryonic day 18 in humans to the twelfth week of fetal life. The stages include gastrulation and formation of the primitive heart tube with rhythmic contractions appearing at day 21, segmentation of the primitive heart tube, looping, realignment of inflow and outflow segments, septation of the atria, ventricles and outflow segments, formation of atrio-ventricular valves, and development of aortic and pulmonary trunks and aortic arches. The genes and factors currently known to be involved in cardiac development are reviewed, but much is still to be determined as the field is evolving with extraordinary rapidity.

Aorta↗

PubMed2002

Naming biology.

Historians of science recite familiar textbook stories about the origin of the term biology. With this note, Peter McLaughlin shows us antecedents that suggest it is worth thinking more about the traditions from which the familiar usage of the term emerged. We invited McLaughlin to submit this addition to our understanding of the foundation of "biology," and we thank him for his willingness to add to our knowledge in this way.

Biology↗

PubMed2002

Quantitative real-time polymerase chain reaction for detection of circulating cells with t(14;18) in volunteer blood donors and patients with follicular lymphoma.

The chromosomal rearrangement t(14;18)(q32;21) involves the major (MBR) or minor (mcr) breakpoint cluster regions and the immunoglobulin heavy chain joining regions (JH) in most follicular lymphomas. As a first step towards determining the clinical significance of circulating cells with t(14;18), we detected and quantitated circulating cells in samples obtained from volunteer blood donors and follicular lymphoma patients. The t(14;18) was co-amplified with beta-actin with real-time quantitative PCR (QRT-PCR) in reactions containing 1 microg of DNA from peripheral blood or bone marrow aspirates. The cell number was quantitated using linear regression and an external standard of serially diluted DNA from cell lines with MBR/JH or mcr/JH rearrangements. At dilutions of 10(5) and 106, sensitivity was 100 and 55% for MBR/JH, and 100 and 10% for mcr/JH rearrangements. Among 102 volunteer blood donors MBR/JH vs. mcr/JH amplicons were detected in 22 vs. 4% with duplicate 1 microg DNA reactions, and in 41 vs. 6% with a total 10 microg DNA analyzed in multiple reactions. Among volunteer blood donors the mean number of circulating cells with MBR/JH vs. mcr/JH rearrangements were 0.8 vs. 0.1/microg DNA, and exceeded the upper normal limit (defined as the mean of all volunteer samples plus two standard deviations) in 3% vs. 2%, respectively. Analysis for MBR/JH rearrangements revealed that follicular lymphoma patients vs. volunteer blood donors were positive in 76% vs. 22% (p = 0.008 by Fisher's exact test); that the mean number of MBR/JH cells per microg of DNA was 91 vs. 0.8 (p = 0.0002 by Mann-Whitney test); and the number of the MBR/JH cells exceeded the upper normal limit in 32% vs. 3% of subjects (p = 0.0001 by Fisher's exact test). Circulating cells with mcr/JH were not detected among any of these 25 lymphoma patients. We conclude that patients with follicular lymphoma are more frequently positive, have higher numbers of circulating cells with t(14;18), which exceed upper normal limit more frequently than in volunteer blood donors.

Blood Cells↗

PubMed2002

Cutaneous and systemic plasmacytosis in a patient of Asian descent living in the United States.

Cutaneous and systemic plasmacytosis is a rare disorder characterized by widely disseminated macular skin eruptions composed of polyclonal lymphoplasmacytic infiltrates associated with variable extracutaneous involvement. Previous reports have been largely restricted to the Japanese literature. We present the first documented case of cutaneous and systemic plasmacytosis in a patient residing in the United States. This 49-year-old man, who had immigrated from Korea 19 years earlier, developed innumerable persistent pink-to-brown macular lesions over his trunk and face. Initial and repeat skin biopsy specimens revealed dense perivascular and periadnexal infiltrates of mature plasma cells, and polyclonal plasmacytosis noted on two different biopsy specimens of mildly enlarged lymph nodes. Multiple tiny pulmonary nodules were found to be of the same histologic appearance. No evidence of clonal immunoglobulin gene rearrangements or human herpesvirus type 8 infection was noted in these biopsy specimens. Treatment with antibiotics, systemic chemotherapy, and anti-CD20 antibody therapy failed to eradicate these lesions, which have persisted for 6 years. This case demonstrates that cutaneous and systemic plasmacytosis can arise in a patient of Asian ancestry, even many years after emigration to the United States.

Humans↗