Biomedical subjects

D Neuberg

Publications and source records attributed to D Neuberg.

At least 37 records · Page 2Linked to original sources

PubMed2001

Comparison of the QTDT analysis for IgE in the CSGA data set.

Over the past few years at least 13 transmission/disequilibrium test (TDT)-based tests have been developed for quantitative (Q) traits for the assessment of association or linkage in the presence of the other. A total of six of these QTDT methods were used to analyze log10IgE in the Collaborative Study on the Genetics of Asthma data set. Only moderate agreement was found between the tests. The results of the QTDT analyses were only slightly affected by the use of gender and age as covariates. Results from analysis of IgE and log10IgE were inconsistent. Our conclusion is that there is only modest agreement among the QTDT methods examined, covariates should be used even if they have a small effect, and that data should be normalized before analysis.

Adult↗

PubMed2001

Global expression changes of constitutive and hormonally regulated genes during endometrial neoplastic transformation.

OBJECTIVE: Endometrioid endometrial carcinoma is caused by a combination of mutational events and hormonal factors. We used large-scale messenger RNA expression analysis to discover genes that distinguish neoplastic transformation and examine the patterns of tumor expression of those genes which are normally regulated during the menstrual cycle. METHODS: Expression of approximately 6000 unique genes was quantified in 4 normal (2 proliferative, 2 secretory) and 10 malignant endometria using Affymetrix Hu6800 GeneChip probe arrays. Expression differences between normal and malignant tissue groups were measured by a test of statistical significance comparing the individual t statistic for each gene to the distribution of maximum t statistics among all genes following 1001 permutations of the tissue group assignments (Permax test). Hormonally responsive genes, selected by comparison of proliferative and secretory subsets of normal endometria using a combination of filters applied to the group means and t test rankings, were then examined in the tumors. RESULTS: Fifty genes with a Permax <0.50 provided excellent discrimination between normal and malignant groups and were predominantly characterized by diminished expression levels in the cancers. We found that 100 genes which are hormonally regulated in normal tissues are expressed in a disordered and heterogeneous fashion in cancers, with tumors resembling proliferative more than secretory endometrium. CONCLUSION: Neoplastic transformation is accompanied by predominant loss of activity of many genes constitutively expressed in normal source tissues and absence of expression profiles which characterize the antitumorigenic progestin response.

Adult↗

PubMed2001

The impact of external beam radiation therapy prior to autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma.

External beam radiation therapy (XRT) is frequently used to treat refractory disease sites or consolidate remission in patients with relapsed non-Hodgkin's lymphoma (NHL) prior to autologous bone marrow transplantation (ABMT). We report the long-term outcome and toxicities associated with this therapy. We uniformly treated 552 patients with NHL with total body irradiation, high-dose chemotherapy, and anti-B-cell monoclonal antibody-purged ABMT. Of these patients, 152 received XRT to the mediastinum, abdomen, or pelvis (n = 102) or other sites (n = 50) prior to ABMT. In this nonrandomized series, there was no difference in progression-free survival between patients treated with XRT and those not treated with XRT. For patients with indolent histology, there was no difference in overall survival between patients treated with XRT and those not treated with XRT. For patients with aggressive histology, the median overall survival time was 64 months in the XRT patients and 79 months in the patients not treated with XRT (P= .09). The risk of acute transplantation-related deaths was not influenced by prior XRT (P = .68). Of patients who received XRT, 12.5% developed secondary myelodysplasia compared with 5.8% of patients not receiving XRT (P = .01). Patients receiving XRT to the mediastinum or axilla had a significantly higher risk of late respiratory death (P = .002). In conclusion, XRT allows refractory patients to become eligible for transplantation and experience a disease-free survival interval equivalent to that of patients who do not receive XRT. However, a higher incidence of non-relapse-associated deaths was observed in patients who received XRT. Future work should explore alternative conditioning strategies and altered timing of XRT, in an attempt to limit these late toxicities.

Adult↗

PubMed2001

MCP-1 modulates chemotaxis by follicular lymphoma cells.

The localization and establishment of follicular lymphoma (FL) cells in distinct anatomic sites probably involves chemokine and adhesion receptors on the neoplastic cells and appropriate chemokines and adhesion receptor ligands in the microenvironment. Several chemokines play an important role in normal B-cell trafficking and differentiation. Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine that induces chemotaxis of a variety of lymphoid cells through its receptor CCR2. CCR2 is also expressed on B cells, and MCP-1 induces chemotaxis of normal B cells. In this report, we investigated expression and function of CCR2 on FL cells. We found FL cells as well as the t(14; 18)+ B-cell lymphoma line H2 expressed CCR2. MCP-1 potentiated SDF-1-induced chemotaxis of FL cells and H2 cells, but MCP-1 alone did not induce chemotaxis. The specificity of the effects of MCP-1 and SDF-1 was demonstrated by antibody blocking studies. Because FL cells are generally associated with follicular dendritic cells (FDCs), FDCs may be an important source of chemokines. We found that cultured FDCs produced MCP-1, and this production was enhanced by tumour necrosis factor. These data implicate MCP-1 in the migration and localization of FL cells.

Antibodies, Monoclonal↗

PubMed2000

Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience.

Acute megakaryocytic leukemia (AMegL) is a rare subtype of acute myeloid leukemia (AML) evolving from primitive megakaryoblasts. Because of its rarity and the lack of precise diagnostic criteria in the past, few series of adults treated with contemporary therapy have been reported. Twenty among 1649 (1.2%) patients with newly diagnosed AML entered on Eastern Cooperative Oncology Group (ECOG) trials between 1984 and 1997 were found to have AMegL. The median age was 42.5 years (range 18-70). Marrow fibrosis, usually extensive, was present in the bone marrow. Of the 8 patients who had cytogenetic studies performed, abnormalities of chromosome 3 were the most frequent. The most consistent immunophenotypic finding was absence of myeloperoxidase in blast cells from 5 patients. In the most typical 3 cases, the leukemic cells were positive for one to 2 platelet-specific antigens in addition to lacking myeloperoxidase or an antigen consistent with a lymphoid leukemia. Myeloid antigens other than myeloperoxidase and selected T-cell antigens (CD7 and/or CD2) were frequently expressed. Induction therapy included an anthracycline and cytarabine in all cases. Complete remission (CR) was achieved in 10 of 20 patients (50%). Two patients remain alive, one in CR at 160+ months. Resistant disease was the cause of induction failure in all but 3 patients. The median CR duration was 10.6 months (range 1-160+ months). The median survival for all patients was 10.4 months (range 1-160+ months). Although half of the patients achieved CR, the long-term outcome is extremely poor, primarily attributable to resistant disease. New therapeutic strategies are needed.

Adolescent↗

PubMed2000

Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen.

BACKGROUND: Although chemotherapy can achieve a high rate of disease remission induction in patients with newly diagnosed acute myelogenous leukemia (AML), patients with recurrent or refractory AML generally have a poorer rate of response. This study assessed the utility of mitoxantrone and intermediate-dose cytarabine (Ara-C) in the treatment of patients with recurrent or refractory AML. METHODS: Forty-seven patients with recurrent or refractory AML were treated with Ara-C, 0.5 gm/m2, intravenously (i.v.) every 12 hours x 12 doses on Days 1-6 and mitoxantrone, 5 mg/m2, i.v. on Days 1-5. RESULTS: Twenty-nine of the 47 patients (62%) achieved a complete response. The median duration of disease remission was 112 days (range, 29 days- 8 years). Of the 25 patients age > or = 60 years, 19 (76%) had a complete disease remission and the median duration of disease remission in this group was 114 days (range, 33-370 days), although all patients subsequently developed a disease recurrence. The chemotherapy generally was well tolerated, with a mean duration of neutropenia of 31 days and a mean duration of thrombocytopenia of 33 days. Three patients died of infectious complications between 23-26 days after the initiation of chemotherapy, 1 patient died of sudden cardiac arrest 13 days after the initiation of chemotherapy, and 1 patient developed cutaneous desquamation. Three patients developed acute cerebellar dysfunction. CONCLUSIONS: The use of mitoxantrone and Ara-C is effective in the treatment of patients with recurrent and refractory AML. The subgroup of patients age > or = 60 years also had a high rate of disease remission induction with this regimen, and the regimen generally was well tolerated.

Adult↗

PubMed2000

Immunoglobulin heavy-chain consensus probes for real-time PCR quantification of residual disease in acute lymphoblastic leukemia.

Tumor-related immunoglobulin heavy-chain (IgH) rearrangements are markers for polymerase chain reaction (PCR) detection of minimal residual disease (MRD) in B-cell malignancies. Nested PCR with patient IgH allele-specific oligonucleotide primers can detect 1 tumor cell in 10(4) to 10(6) normal cells. In childhood acute lymphoblastic leukemia (ALL), persistence of PCR-detectable disease is associated with increased risk of relapse. The clinical significance of qualitative PCR data can be limited, however, because patients can harbor detectable MRD for prolonged periods without relapse. Recent studies indicate that a quantitative rise in tumor burden identifies patients who are at high risk for relapse. Therefore, an efficient and reliable PCR method for MRD quantification is needed for ALL patients. We have developed a real-time PCR method to quantify MRD with IgH V(H) gene family consensus fluorogenically labeled probes. With this method, a small number of probes can be used to quantify MRD in a large number of different patients. The assay was found to be both accurate and reproducible over a wide range and capable of detecting approximately 1 tumor cell in 5 x 10(4) normal cells. We demonstrate that this methodology can discriminate between patients with persistence of MRD who relapse and those who do not. This technique is generally applicable to B-cell malignancies and is currently being used to quantify MRD in a number of prospective clinical studies at our institution. (Blood. 2000;95:2651-2658)

Base Sequence↗

PubMed2000

Reconstitution of T-cell receptor repertoire diversity following T-cell depleted allogeneic bone marrow transplantation is related to hematopoietic chimerism.

CDR3 spectratyping was used to analyze the complexity of the T-cell repertoire and to define the mechanisms and kinetics of the reconstitution of T-cell immunity after allogeneic bone marrow transplantation (BMT). This method, which is based on polymerase chain reaction amplification of all CDR3 regions using the T-cell receptor (TCR) Vbeta genes, was used to examine serial samples of peripheral blood lymphocytes from 11 adult patients with chronic myelogenous leukemia (CML) who underwent T-cell-depleted allogeneic BMT. In contrast to 10 normal donors who display highly diverse and polyclonal spectratypes, patient samples before and early after BMT revealed markedly skewed repertoires, consisting of absent, monoclonal, or oligoclonal profiles for the majority of Vbeta subfamilies. To quantify changes in TCR repertoire over time, we established an 8-point scoring system for each Vbeta subfamily. The mean complexity score for patient samples before transplant (130.8) was significantly lower than that for normal donors (183; P = 0. 0007). TCR repertoire complexity was abnormal in all patients at 3 months after BMT (mean score = 87). Normalization of repertoire began in 4 patients at 6 months after BMT, but the majority of patients continued to display abnormal repertoires for up to 3 years after BMT. To determine whether the reconstituted T-cell repertoire was derived from the donor or recipient, unique microsatellite loci were examined to establish chimeric status. At 3 months after BMT, 7 patients demonstrated mixed chimerism; 4 had complete donor hematopoiesis (CDH). CDH strongly correlated with likelihood of restoration of T-cell repertoire complexity (P = 0.003). In contrast, patients who demonstrated persistence of recipient hematopoiesis failed to reconstitute a diverse TCR repertoire. These findings suggest that the reconstitution of a normal T-cell repertoire from T-cell progenitors in adults is influenced by interactions between recipient and donor hematopoietic cells. (Blood. 2000;95: 352-359)

Adult↗

PubMed2000

Acute respiratory symptoms in workers exposed to vanadium-rich fuel-oil ash.

BACKGROUND: Occupational exposure to fuel-oil ash, with its high vanadium content, may cause respiratory illness. It is unclear, however, what early acute health effects may occur on the pathway from normal to compromised respiratory function. METHODS: Using a repeated measures design, we studied prospectively 18 boilermakers overhauling an oil-fired boiler and 11 utility worker controls. Subjects completed a respiratory symptom diary five times per day by using a 0-3 scale where 0=symptom not present, 1=mild symptom, 2=moderate symptom, and 3=severe symptom. Daily symptom severity was calculated by using the highest reported score each day for upper and lower respiratory symptoms. Daily symptom frequency was calculated by summing all upper or lower airway symptom reports, then dividing by number of reporting times. Respiratory symptom frequency and severity were analyzed for dose-response relationships with estimated vanadium and PM(10) doses to the lung and upper airway by using robust regression. RESULTS: During the overhaul, 72% of boilermakers reported lower airway symptoms, and 67% reported upper airway symptoms. These percentages were 27 and 36 for controls. Boilermakers had more frequent and more severe upper and lower respiratory symptoms compared to utility workers, and this difference was greatest during interior boiler work. A statistically significant dose-response pattern for frequency and severity of both upper and lower respiratory symptoms was seen with vanadium and PM(10) in the three lower exposure quartiles. However, there was a reversal in the dose-response trend in the highest exposure quartile, reflecting a possible healthy worker effect. CONCLUSIONS: Boilermakers experience more frequent and more severe respiratory symptoms than utility workers. This is most statistically significant during boiler work and is associated with increasing dose estimates of lung and nasal vanadium and PM(10).

Adult↗

PubMed2000

Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple myeloma after donor lymphocyte infusion.

Recent reports of clinical responses following donor lymphocyte infusions (DLI) in patients with relapsed multiple myeloma (MM) after allogeneic BMT have demonstrated the ability of allogeneic cells to mediate a graft-versus-myeloma (GVM) effect, but the mechanisms involved have not been determined. To identify changes in the T cell compartment associated with DLI, we performed a molecular analysis of the T cell receptor (TCR) repertoire in four patients with relapsed MM who received infusions of CD4+ lymphocytes from HLA-identical sibling donors. Three of the four patients demonstrated a clinical anti-myeloma response following DLI but also developed graft-versus-host disease (GVHD). The TCR repertoire was examined after PCR amplification of 24 Vbeta gene subfamilies. This method determines the relative utilization of each Vbeta gene subfamily and also allows the identification of clonal and oligoclonal T cell populations through analysis of CDR3 regions for each TCR Vbeta gene subfamily. Serial blood samples were obtained over at least a 1 year period before and after DLI and results compared to 10 normal donors. Serial analysis of CDR3 size profiles demonstrated the appearance of clonal T cell populations after DLI in each of the three responding patients. The appearance of some clones was noted within the first 3 months after DLI and coincided with decreasing levels of monoclonal paraprotein indicating an ongoing GVM response. Other T cell clones appeared at later time points and coincided with the development of GVHD. These findings demonstrate that T cell clones with different patterns of onset can be identified in the peripheral blood of MM patients following DLI. Further functional characterization of these distinct clonal expansions will be required to determine whether these T cell clones are mediators of either anti-myeloma or anti-host activity.

Adult↗

PubMed2000

Oral magnesium pidolate: effects of long-term administration in patients with sickle cell disease.

Prevention of erythrocyte dehydration by specific blockade of the transport pathways promoting loss of potassium (K) is a potential therapeutic strategy for sickle cell (SS) disease. Dietary magnesium (Mg) pidolate supplementation over a 4-week period has been shown to inhibit K-Cl co-transport and reduce dehydration. We report here the results in 17 of 20 patients with SS disease treated in an open-label unblinded study of the effects of long-term (6 months) oral Mg pidolate administration (540 mg Mg/d). A significant decrease (P < 0.0025) was observed with Mg therapy in the distribution widths for red cell mean cell haemoglobin concentration (MCHC) (haemoglobin distribution width; HDW), reticulocyte mean cell volume (red cell distribution width of reticulocytes; RDWr) and MCHC (reticulocyte HDW; HDWr), activity of red cell K-Cl co-transport, Na/Mg exchanger and Ca2+-activated (Gardos) K+ channel, whereas red cell K and Mg contents were significantly increased. Hb levels and absolute reticulocyte counts did not change with Mg therapy. Two patients did not complete the trial because of diarrhoea and one did not complete the trial for unrelated reasons. Although the median number of painful days in a 6-month period decreased from 15 (range 0-60) in the year before the trial to 1 (range 0-18; P < 0.0005) during the period of Mg therapy, no firm conclusion on therapeutic efficacy could be drawn from this unblinded open-label trial.

Administration, Oral↗

PubMed2000

Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia.

The effectiveness of donor-lymphocyte infusion (DLI) for treatment of relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation is a clear demonstration of the graft-versus-leukemia (GVL) effect. T cells are critical mediators of GVL, but the antigenic targets of this response are unknown. To determine whether patients who respond to DLI also develop B-cell immunity to CML-associated antigens, we analyzed sera from three patients with relapsed CML who achieved a complete molecular remission after infusion of donor T cells. Sera from these individuals recognized 13 distinct gene products represented in a CML-derived cDNA library. Two proteins, Jkappa-recombination signal-binding protein (RBP-Jkappa) and related adhesion focal tyrosine kinase (RAFTK), were recognized by sera from three of 19 DLI responders. None of these antigens were recognized by sera from healthy donors or patients with chronic graft-versus-host disease. Four gene products were recognized by sera from CML patients treated with hydroxyurea and nine were detected by sera from CML patients who responded to IFN-alpha. Antibody titers specific for RAFTK, but not for RBP-Jkappa, were found to be temporally associated with the response to DLI. These results demonstrate that patients who respond to DLI generate potent antibody responses to CML-associated antigens, suggesting the development of coordinated T- and B-cell immunity. The characterization of B cell-defined antigens may help identify clinically relevant targets of the GVL response in vivo.

Antibodies, Neoplasm↗

PubMed2000

Characteristics and outcome of children with Beckwith-Wiedemann syndrome and Wilms' tumor: a report from the National Wilms Tumor Study Group.

PURPOSE: Children with Beckwith-Wiedemann syndrome (BWS) are at increased risk for developing Wilms' tumor (WT). We reviewed the National Wilms Tumor Study Group (NWTSG) records to assess clinical characteristics and outcome of patients with WT and BWS. METHODS: In the NWTSG, treating clinicians were asked to report, for each enrolled patient, whether the patient had BWS. Between 1980 and 1995, 4,669 patients were treated on two consecutive NWTSG protocols (NWTS 3 and NWTS 4). We retrospectively reviewed the clinical characteristics and treatment outcomes of BWS patients compared with patients with WT without BWS. RESULTS: Fifty-three children enrolled onto NWTS 3 and 4 were reported to have BWS. BWS patients were more likely to present with lower-stage tumors (P =.0001), with more than half (27 of 53) presenting with stage I disease. The overall treatment outcomes for the BWS patients were nearly identical to those without BWS, with overall survival at 4 years from diagnosis at 89% and 90%, respectively. Overall, 21% of the patients with BWS had bilateral disease, either at diagnosis (nine of 53) or as metachronous contralateral recurrence (two of 53). BWS patients enrolled onto NWTS 4 had smaller tumors than those enrolled onto NWTS 3 (P =.02), a trend not seen in the non-BWS patients. CONCLUSION: Like children without BWS, children with BWS and WT have an excellent prognosis with modern treatment regimens. There is a high risk of bilateral disease, and increasingly smaller tumors are being detected. This suggests that a national trial assessing the role of ultrasound screening followed by nephron-sparing surgery for some patients may be appropriate.

Beckwith-Wiedemann Syndrome↗

PubMed2000

Tandem high-dose therapy in rapid sequence for children with high-risk neuroblastoma.

PURPOSE: Advances in chemotherapy and supportive care have slowly improved survival rates for patients with high-risk neuroblastoma. The focus of many of these chemotherapeutic advances has been dose intensification. In this phase II trial involving children with advanced neuroblastoma, we used a program of induction chemotherapy followed by tandem high-dose, myeloablative treatments (high-dose therapy) with stem-cell rescue (HDT/SCR) in rapid sequence. PATIENTS AND METHODS: Patients underwent induction chemotherapy during which peripheral-blood stem and progenitor cells were collected and local control measures undertaken. Patients then received tandem courses of HDT/SCR, 4 to 6 weeks apart. Thirty-nine patients (age 1 to 12 years) were assessable, and 70 cycles of HDT/SCR were completed. RESULTS: Pheresis was possible in the case of all patients, despite their young ages, with an average of 7.2 x 10(6) CD34(+) cells/kg available to support each cycle. Engraftment was rapid; median time to neutrophil engraftment was 11 days. Four patients who completed the first HDT course did not complete the second, and there were three deaths due to toxicity. With a median follow-up of 22 months (from diagnosis), 26 of 39 patients remained event-free. The 3-year event-free survival rate for these patients was 58%. CONCLUSION: A tandem HDT/SCR regimen for high-risk neuroblastoma is a feasible treatment strategy for children and may improve disease-free survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Assessment of the stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin's disease: Eastern Cooperative Oncology Group pilot study E1492.

PURPOSE: This study was performed, in a multi-institutional setting, to evaluate the efficacy and feasibility of the Stanford V chemotherapy regimen plus radiotherapy to bulky Hodgkin's disease sites. PATIENTS AND METHODS: A two-stage design was implemented in a phase II study involving 47 patients with bulky mediastinal stage I/II or stage III/IV Hodgkin's disease. Twelve weeks of the Stanford V chemotherapy regimen were given with consolidative radiotherapy (36 Gy) to lymph nodes >/= 5 cm and/or macroscopic splenic disease. Treatment was administered in one of five institutions participating in the Eastern Cooperative Oncology Group. RESULTS: With a median follow-up of 4.8 years, 45 patients are alive and 40 have been continuously disease-free. The estimated freedom from progression was 87% at 2 years and 85% at 5 years. Overall survival was 96% at 2 and 5 years. There was one death from Hodgkin's disease and one death from an M5 acute leukemia. Six of seven relapsed patients received high-dose therapy and autologous stem-cell transplantation. The freedom from second progression for the seven relapsed patients was estimated at 98% at 3 years. CONCLUSION: Stanford V chemotherapy and consolidative radiotherapy to bulky disease is effective in bulky and advanced Hodgkin's disease in a multi-institutional setting. On this basis, an Intergroup study comparing doxorubicin, bleomycin, vinblastine, and dacarbazine with the Stanford V regimen has been initiated.

Adolescent↗

PubMed2000

CHOP chemotherapy with preemptive granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma: a dose-intensity analysis.

This prospective trial was designed to determine the safety and efficacy of full-dose, on-time chemotherapy in elderly patients with aggressive non-Hodgkin's lymphoma. Twenty patients (median age, 71 years; range, 66 to 80 years) were enrolled in a phase II, multicenter trial to receive cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) supported by granulocyte colony-stimulating factor (G-CSF). CHOP was given in standard doses. Six cycles were planned every 21 days, with G-CSF starting on day 3 and continuing until the absolute neutrophil count was greater than 10,000/microL. Consolidation radiation therapy was permitted. Restaging was performed following cycles 4 and 6. By the age-adjusted International Prognostic Index, four patients were low, 10 were low-intermediate, four were high-intermediate, and two were high risk. Eighteen cases completed all 6 cycles. The average cycle length for all 112 cycles was 21.7 days. The dose intensities (corrected for delay) for each agent were cyclophosphamide 97.3%, doxorubicin 97.3%, vincristine 91.5%, and prednisone 97.3%. Treatment-related complications included grade 4 leukopenia and grade 4 thrombocytopenia in 11.6% and 3.6% of cycles, respectively. Hospitalization for neutropenia and fever was needed for 7.1% of cycles. There was no grade 3/4 cardiac toxicity. No treatment-related mortality occurred. All toxicities were reversible. There were 12 (60%) complete responses, four (20%) gallium-negative partial responses, and four patients (20%) with progressive disease. With a median follow-up of 2.29 years, progression-free and overall survival rates at 2 years are 42% (90% confidence interval: 23%-61%) and 66% (90% confidence interval: 47%-85%), respectively. Using preemptive G-CSF, full-dose CHOP can be administered safely to elderly patients.

Aged↗

PubMed2000

When is hilar uptake of 67Ga-citrate indicative of residual disease after CHOP chemotherapy?

UNLABELLED: The purpose of this study was to evaluate the prevalence and characterize the patterns of hilar uptake (HU) on 67Ga-citrate imaging after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimens for non-Hodgkin's lymphoma (NHL), to differentiate hilar lymphoma (HL) from HU of benign etiology. METHODS: A total of 930 studies (698 planar, 232 thoracic SPECT) was reviewed retrospectively in 100 NHL patients (29 low-grade, 60 intermediate-grade, and 11 high-grade) treated with CHOP and followed up longitudinally with serial gallium studies (planar: median, 7; range, 3-16 studies in 100 patients; SPECT: median, 1; range, 0-11 studies in 72 patients) over a median duration of 36 mo (range, 6-112 mo) from diagnosis. Clinical outcome and size changes over time on correlative CT and/or radiographs were used to evaluate benign versus malignant changes within the hila. RESULTS: HU after CHOP was present in 79% of patients (90% confidence interval [CI], 71%-85%), with 33% showing HU on SPECT alone. Once present, HU persisted for a median of 27 mo (range, 2-84 mo) from onset. The prevalence of HU and HL at various time points was as follows: baseline HU, 52% with HL 60%; mid-CHOP HU, 59% with HL2%; post-CHOP HU, 52% with HL6%; follow-up HU, 76% with HL 9%. HU of benign etiology was not significantly correlated with CHOP dosage. HU was symmetric in 90% of patients (90% CI, 82%-95%) and less intense than the original disease in 89% of patients (90% CI, 80%-95%), and these features were highly predictive of benign etiology (negative predictive value [NPV], 98.6% if symmetric; NPV, 96.5% if less than original disease; NPV, 100% if both present). Asymmetric HU equal in intensity to the original disease, however, was highly predictive of HL (positive predictive value [PPV], 87.5% if asymmetric; PPV, 85.7% if equal to original disease; PPV, 100% if both present). CONCLUSION: HU after CHOP is common (overall incidence, 79%), often seen only on SPECT, and most likely of benign etiology when symmetric and less intense than the original disease. Asymmetric HU that equals the intensity of the original disease, however, is a possible indicator for HL.

Adult↗

PubMed1999

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↗