Biomedical subjects

David J Inwards

Publications and source records attributed to David J Inwards.

At least 19 recordsLinked to original sources

PubMed2006

A pilot study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated, diffuse large B-cell lymphoma.

BACKGROUND: In this pilot study, the authors assessed the feasibility of combination epratuzumab and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (ER-CHOP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: Patients received chemotherapy on the following schedule: epratuzumab 360 mg/m2, rituximab 375 mg/m2, and standard-dose CHOP every 3 weeks for 6 to 8 cycles. The primary endpoint was the incidence of grade 4 neutropenia and grade 3 or 4 antibody infusional toxicity. Secondary endpoints were the complete response (CR) rate, the overall response rate (ORR), and progression-free survival (PFS). Weekly blood counts were obtained to monitor hematologic toxicity. Fifteen patients were enrolled and treated. Baseline patient characteristics included a median age of 63 years (range, 42-78 years), 60% of patients had stage III or IV disease, 7 patients had a low-risk International Prognostic Index (IPI) score (0 or 1), 7 patients had an intermediate-risk IPI score (2 or 3), and 1 patient was high risk. RESULTS: Grade 3 or 4 neutropenia was observed in 14 patients (93%) or in 28 of 92 treatment cycles (30%). Three patients developed grade > or =3 infection or fever. Eleven patients (73%) required dose reductions. No grade 3 antibody infusion-related toxicity was reported. Thirteen of 15 patients responded (ORR, 87%,), including 10 CRs (67%), 3 partial responses (20%), 1 patient with stable disease, and 1 patient with disease progression. At a median follow-up of 30 months, 13 of 15 patients remained alive. The 1-year PFS and OS rates were 93% and 100%, respectively; and the 2-year PFS and OS rates were 86% and 86%, respectively. CONCLUSIONS: ER-CHOP every 21 days was feasible as treatment for newly diagnosed patients with DLBCL. A Phase II multicenter study is underway.

Adult↗

PubMed2006

Absolute lymphocyte count predicts overall survival in follicular lymphomas.

The peripheral blood absolute lymphocyte count (ALC) recovery after autologous stem cell transplantation has been shown to be an independent prognostic factor for survival for different haematologic malignancies. The role of ALC at diagnosis for follicular (grades 1 and 2) lymphomas (FL) on survival is not well described. The primary objective of this study was to assess the role of ALC on overall survival (OS) in FL patients. Of 1104 FL patients, 228 patients were originally diagnosed, followed, and had all treatment at the Mayo Clinic from 1984 and 1999, were evaluated. The median follow-up was 89 months (range: 8.35-248). ALC as a continuous variable was identified as a predictor for OS [Hazard ratio (HR) = 0.74, P < 0.04]. ALC >/= 1.0 x 10(9)/l (n = 164) predicted a longer OS versus ALC < 1.0 x 10(9)/l (n = 64; 175 vs. 73 months respectively, P < 0.0001). When compared with the Follicular Lymphoma International Prognostic Index (FLIPI), ALC was an independent prognostic factor for OS by multivariate analysis (HR = 0.677, P < 0.0001). These data suggest a critical role of FL patients' immune status at diagnosis on survival.

Follow-Up Studies↗

PubMed2006

Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation.

The immunoglobulin free light chain (FLC) is the precursor protein of amyloid in primary systemic amyloidosis (AL). Historically, the ability to monitor the amyloid protein precursor protein has been crude. We evaluated the utility of the FLC assay in a retrospective analysis of patients with AL undergoing peripheral blood stem cell transplantation (PBSCT). Ninety-three such patients had serial FLC measurements performed. The prognostic effects of the initial concentration and the extent of reduction of monoclonal FLC on survival were studied. There was a significantly higher risk of death in patients with higher baseline FLC (hazard ratio 2.6, P < .04). Baseline FLC correlated with serum cardiac troponin levels, and higher FLC levels were associated with more organs involved by amyloid, suggesting that high FLC levels may be associated with more advanced disease. The percent FLC reduction did not predict for survival, but the absolute level of FLC achieved after therapy did. Normalization of FLC level after PBSCT predicted for both organ response and complete hematologic response. Achievement of FLC response was a better predictor of survival than achievement of complete hematologic response or normalization of the FLC ratio. FLC measurements both before and after PBSCT are important predictors of patient outcome.

Adult↗

PubMed2006

Radioimmunotherapeutic strategies in autologous hematopoietic stem-cell transplantation for malignant lymphoma.

High-dose therapy followed by autologous hematopoietic stem-cell transplantation is the preferred therapy for relapsed chemotherapy-sensitive aggressive non-Hodgkin lymphoma, and may play a role in the treatment of high-risk first-remission aggressive lymphomas, mantle-cell lymphomas and relapsed follicular lymphomas. The primary cause of failure of this approach is disease recurrence despite initial responses. Traditional high-dose regimens have relied upon myeloablative combinations of chemotherapy with or without total body irradiation. In the Western world, over 90% of lymphomas are of B-cell origin, and the vast majority of those that come to transplant remain CD20-positive. The development of radioimmunotherapeutic approaches targeting this antigen allows for either dose escalation with stem-cell support, or the addition of targeted therapy to conditioning regimens either as a replacement for total body irradiation or in addition to myeloablative chemotherapy regimens. Results to date with yttrium-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar) suggest that the addition of radioimmunoconjugate therapy to conventional conditioning regimens results in a toxicity profile similar to that seen with chemotherapy conditioning alone. Demonstration of improved disease control will ultimately require phase-III studies, though preliminary results are promising.

Dose-Response Relationship, Radiation↗

PubMed2006

The International Prognostic Index predicts outcome after histological transformation of low-grade non-Hodgkin lymphoma.

Histological transformation of low-grade non-Hodgkin lymphoma (NHL) to diffuse large cell NHL is well recognized and is associated with a poor prognosis. We sought to determine the overall outcome and the factors that affect survival in patients with histological transformation of low-grade NHL. Between November 1979 and September 2000, 93 patients who developed transformed lymphoma were identified. The median time to transformation was 4.2 years from the original diagnosis. The median age at transformation was 63 years. Seventy-eight percent had stage III or IV disease. Fifty-seven percent had extranodal involvement, including bone marrow; 33% had an elevated lactate dehydrogenase. The International Prognostic Index (IPI) at transformation was termed the transformation IPI (tIPI); 29% had a tIPI of 0-1, 59% had a tIPI of 2-3 and 8% had a tIPI of 4-5. At a median follow-up of 15 months from histological transformation, 20 of 93 patients (22%) were alive. The median survival from transformation was 15 months (4 months to 19.7 years). On univariate analysis, the following factors at the time of histological transformation were associated with an improved survival: low tIPI (P = 0.009), time to transformation > 4 years (P = 0.02), age < or = 60 years (P = 0.02) and stage I or II disease (P = 0.04). On multivariate analysis, factors that remained significant included a low tIPI (P = 0.0001) and a time to transformation > 4 years (P = 0.004). tIPI correlated with overall survival (OS); IPI 0-1, median OS 38 months; IPI 2-3, median OS 12 months; IPI 4-5, median OS 4 months. In conclusion, tIPI at the time of histological transformation is an important predictor of OS. A time to transformation > 4 years from diagnosis is associated with better OS.

Adult↗

PubMed2006

Timing of autologous stem cell transplantation from last chemotherapy affects lymphocyte collection and survival in non-Hodgkin lymphoma.

Autograft absolute lymphocyte count (A-ALC) is a prognostic factor for survival in non-Hodgkin lymphoma (NHL) after autologous stem cell transplantation (ASCT). An A-ALC is dependent upon the preaphaeresis absolute lymphocyte count (PA-ALC) at the time of aphaeresis. It was hypothesised that the time interval from last chemotherapy (TILC) to aphaeresis affects PA-ALC. One hundred and sixty consecutive NHL patients who underwent ASCT at the Mayo Clinic between 1996 and 2001 were evaluated. A strong correlation between TILC and PA-ALC (r = 0.67, P < 0.0001) was identified. Higher PA-ALC was observed in TILC > or =55 d compared with TILC <55 d [median: 7.0 vs. 3.8 x 10(9)/l], P < 0.0001). TILC as a continuous variable was identified as a prognostic factor for overall survival (OS) [hazard ratio (HR) = 0.989, P < 0.01] and progression-free survival (PFS) (HR = 0.992, P < 0.0492). Median OS and PFS were longer in the TILC > or =55 d vs. TILC <55 d group (not reached vs. 21 months, P < 0.0008; 76 vs. 9 months, P < 0.0025, respectively). Multivariate analysis demonstrated TILC to be an independent prognostic indicator for OS and PFS. These findings suggest that the immune status of the host at the time of aphaeresis may predict survival after ASCT.

Adult↗

PubMed2006

Combined positron emission tomography/computed tomography for evaluation of presumed choroidal metastases.

BACKGROUND: Choroidal metastases are the most common intraocular malignancy and are the first sign of systemic malignancy in approximately one-third of patients. Of patients with no previous diagnosis of cancer, oncological evaluation fails to find the primary lesion in approximately 50% of cases. Newer imaging modalities such as combined positron emission tomography/computed tomography (PET/CT) may improve the yield of the systemic work-up. METHODS: Consecutive patients presenting with presumed choroidal metastases were evaluated with whole body combined PET/CT scanning. RESULTS: Four patients presenting to a tertiary referral hospital with choroidal metastases as the first sign of systemic malignancy were evaluated. In all four cases, PET/CT demonstrated the ocular lesion, and the primary malignancy which was confirmed by tissue biopsy. False-negative results were seen in two cases of cerebral metastases. PET/CT demonstrated lesions not visible on CT or magnetic resonance imaging in two cases. CONCLUSIONS: Combined PET/CT is a useful addition to the work-up of patients with choroidal metastases. It provides the opportunity to detect lesions not visible with other imaging modalities and the ability to image patients with contraindications to magnetic resonance imaging. It is essential to correlate PET images with clinical information and the results of other imaging modalities and tissue biopsy remains the gold standard in the diagnosis of malignancy. False positives and negatives can occur with PET/CT, and further research is needed before this promising technology becomes a routine part of the evaluation of patients with choroidal metastases.

Adult↗

PubMed2006

Response to rituximab in patients with type II cryoglobulinemia.

Type II cryoglobulinemia (CG) is a heterogeneous, generally indolent disorder caused by a monoclonal antibody with activity against polyclonal antibodies and is commonly associated with hepatitis C, lymphoproliferative disorders (LPDs), or autoimmune diseases. It can lead to substantial morbidity, including renal failure, cutaneous ulcers, or neuropathy. Medical records were reviewed for 8 patients with previously treated symptomatic CG who were part of a prospectively held dysproteinemia database. Patients subsequently received 14 total courses of rituximab treatment (standard infusion, 375 mg/m2 for 4 or 8 doses) between February 1999 and March 2005. One patient had essential CG, and 1 had Gaucher disease with hypersplenism. Six patients had an LPD, and 4 of them had concomitant disorders (2 with hepatitis C and 2 with Sjogren syndrome). Treatment indications included purpura, LPD, cutaneous ulcers, and renal failure. Clinical improvement was evaluated by improved cryocrit, total complement, C4, and rheumatoid factor. Six patients had some clinical improvement. Cutaneous manifestations were the most responsive; renal disease and lymphoma were more refractory. Laboratory values showed improvement after 7 of 12 available treatment courses. No adverse reactions were noted. Overall, rituximab appears to be a safe and effective therapy.

Antibodies, Monoclonal↗

PubMed2005

Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma.

PURPOSE: Mantle cell lymphoma (MCL) is characterized by a t(11;14) resulting in overexpression of cyclin D1 messenger RNA. This study tested whether temsirolimus (previously known as CCI-779), an inhibitor of the mammalian target of rapamycin kinase that regulates cyclin D1 translation, could produce tumor responses in patients with MCL. PATIENTS AND METHODS: Patients with relapsed or refractory MCL were eligible to receive temsirolimus 250 mg intravenously every week as a single agent. Patients with a tumor response after six cycles were eligible to continue drug for a total of 12 cycles or two cycles after complete remission, and were then observed without maintenance. RESULTS: Thirty-five patients were enrolled and were assessable for toxicity; one patient had MCL by histology but was cyclin D1 negative and was ineligible for efficacy. The median age was 70 years (range, 38 to 89 years), 91% were stage 4, and 69% had two or more extranodal sites. Patients had received a median of three prior therapies (range, one to 11), and 54% were refractory to the last treatment. The overall response rate was 38% (13 of 34 patients; 90% CI, 24% to 54%) with one complete response (3%) and 12 partial responses (35%). The median time-to-progression in all patients was 6.5 months (95% CI, 2.9 to 8.3 months), and the duration of response for the 13 responders was 6.9 months (95% CI, 5.2 to 12.4 months). Hematologic toxicities were the most common, with 71% (25 of 35 patients) having grade 3 and 11% (four of 35 patients) having grade 4 toxicities observed. Thrombocytopenia was the most frequent cause of dose reductions but was of short duration, typically resolving within 1 week. CONCLUSIONS: Single-agent temsirolimus has substantial antitumor activity in relapsed MCL. This study demonstrates that agents that selectively target cellular pathways dysregulated in MCL cells can produce therapeutic benefit. Further studies of this agent in MCL and other lymphoid malignancies are warranted.

Adult↗

PubMed2005

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis.

PURPOSE: Absolute lymphocyte count recovery at day 15 (ALC-15) post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival for multiple hematologic malignancies and metastatic breast cancer. The relationship of ALC-15 with clinical outcomes in primary systemic amyloidosis is unknown. EXPERIMENTAL DESIGN: We evaluated 145 consecutive patients with primary systemic amyloidosis who underwent ASCT at the Mayo Clinic from 1996 to 2003. The ALC-15 threshold was set at 500 cells/microL based on our previous observations. RESULTS: The median patient follow-up was 22 months (range, 3-87 months). Higher hematologic complete response was observed in patients with an ALC-15 > or = 500 cells/microL compared with patients with an ALC-15 < 500 cells/microL (41% versus 21%, P < 0.0008, respectively). The median overall survival and progression-free survival times were significantly better for the 59 patients that achieved an ALC-15 > or = 500 cells/microL compared with 86 patients with ALC-15 < 500 cells/microL (not reached versus 53 months, P < 0.0003 and not reached versus 27 months, P < 0.0001, respectively). Multivariate analysis showed ALC-15 to be an independent prognostic factor for overall survival and progression-free survival. CONCLUSIONS: ALC-15 > or = 500 cells/microL is associated with significantly improved clinical outcomes following ASCT in patients with primary systemic amyloidosis.

Adult↗

PubMed2005

Oprelvekin-associated bilateral optic disk edema.

PURPOSE: To report a case of bilateral optic disk edema in a patient taking oprelvekin for radioimmunotherapy-induced thrombocytopenia. DESIGN: Observational case report. METHODS: A 38-year-old man with a history of relapsed non-Hodgkins follicular lymphoma complained of bilateral loss of vision following oprelvekin therapy for thrombocytopenia. RESULTS: Funduscopic examination demonstrated bilateral optic disk edema with exudates inferotemporal to the right nerve. The results of magnetic resonance imaging of the brain and orbits and lumbar puncture were normal. The disk edema resolved with discontinuation of oprelvekin therapy. CONCLUSIONS: Oprelvekin therapy may be associated with bilateral optic disk edema. This has been shown to be reversible in a primate model.

Adult↗

PubMed2005

The effect of absolute lymphocyte count recovery kinetics on survival after autologous stem cell transplantation for non-Hodgkin's lymphoma.

Absolute lymphocyte count (ALC) >or=500 cells/microl at day 15 after autologous stem cell transplantation (ASCT) is a powerful independent, prognostic indicator for survival in multiple hematological malignancies. A limitation in these studies was the selection of a single time point (day 15 post-ASCT) as the only discriminator of clinical outcome in relation to ALC recovery. We hypothesized there is a continuous and not discrete relationship between ALC recovery and clinical outcome post-ASCT in NHL. Therefore, we analyzed 274 consecutive patients who underwent ASCT for NHL between 1987 and 2001. The primary end point was to assess the impact of the kinetics of post-ASCT lymphocyte recovery>or=500 cells/microl (K-ALC) on overall survival (OS) and progression-free survival (PFS). K-ALC was a predictor of OS and PFS when the Cox proportional hazards model was used with K-ALC entered as a continuous variable (p<0.0001). Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that the K-ALC post-ASCT is associated with clinical outcome in NHL.

Adolescent↗

PubMed2005

Primary lymphomas of bone.

Primary bone lymphoma is rare. The majority of cases are diffuse large B-cell non-Hodgkin's lymphomas. Classification, staging, and treatment are controversial. The relatively small number of cases has led to many case reports and series describing institutional experiences but precludes the use of randomized clinical trials to address the question of optimal management. This article will review clinical and radiologic presentations, diagnostic techniques, and histologic characteristics. Most important, it will present what limited information we do have regarding effective treatment options for this unusual type of lymphoma.

Femoral Neoplasms↗

PubMed2005

How to interpret and pursue an abnormal complete blood cell count in adults.

A complete blood cell count (CBC) is one of the most common laboratory tests in medicine. For example, at our institution alone, approximately 1800 CBCs are ordered every day, and 10% to 20% of results are reported as abnormal. Therefore, it is in every clinician's interest to have some understanding of the specific test basics as well as a structured action plan when confronted with abnormal CBC results. In this article, we provide practical diagnostic algorithms that address frequently encountered conditions associated with CBC abnormalities including anemia, thrombocytopenia, leukopenia, polycythemia, thrombocytosis, and leukocytosis. The objective is to help the nonhematologist recognize when a subspecialty consultation is reasonable and when it may be circumvented, thus allowing a cost-effective and intellectually rewarding practice.

Adult↗

PubMed2004

Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation.

Primary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot data suggest survival is better in patients undergoing peripheral blood stem cell transplantation (PBSCT), but the selection process makes the apparent benefit suspect. We have reported that circulating cardiac biomarkers are the best predictors of survival outside of the transplantation setting. We now test whether cardiac troponins (cTnT and cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are prognostic in transplant recipients. In 98 patients with AL undergoing PBSCT, serum cardiac biomarkers were measured (cTnT, 98 patients; cTnI, 65 patients; and NT-proBNP, 63 patients). Elevated levels of cTnT, cTnI, and NT-proBNP were present in 14%, 43%, and 48% of patients, respectively. At 20 months median follow-up, median survival has not been reached for patients with values below the thresholds; in patients with values above the thresholds, median survival is 26.1 months, 66.1 months, and 66.1 months, respectively. Our previously reported risk systems incorporating these markers were also prognostic, notably the cTnT/NT-proBNP staging. Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT.

Adult↗

PubMed2004

Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study.

Primary systemic amyloidosis (AL) is a plasma cell dyscrasia resulting in multisystem failure and death. High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has been associated with higher response rates and seemingly higher overall survival than standard chemotherapy. Selection bias, however, confounds interpretation of these results. We performed a case-match-control study comparing overall survival of 63 AL patients undergoing transplantation with 63 patients not undergoing transplantation. Matching criteria included age, sex, time to presentation, left ventricular ejection fraction, serum creatinine, septal thickness, nerve involvement, 24-hour urine protein, and serum alkaline phosphatase. According to design, there was no difference between the groups with respect to sex (57% males), age (median, 53 years), left ventricular ejection fraction (65%), number of patients with peripheral nerve involvement (17%), cardiac interventricular septal wall thickness (12 mm), serum creatinine (1.1 mg/dL [97.24 micromol/L]), and bone marrow plasmacytosis (8%). Sixty-six patients have died (16 cases and 50 controls). For PBSCT and control groups, respectively, the 1-, 2-, and 4-year overall survival rates are 89% and 71%; 81% and 55%; and 71% and 41%. Outside a randomized clinical trial, these results present the strongest data supporting the role of PBSCT in selected patients with AL.

Adult↗

PubMed2004

Therapeutic options in patients with lymphoma and severe liver dysfunction.

OBJECTIVES: To determine the long-term outcome of patients presenting with synchronous lymphoma and severe liver dysfunction and to describe the outcome of patients treated with initial mechlorethamine-based therapy used as a bridge to more conventional chemotherapy. PATIENTS AND METHODS: We reviewed the clinical course of all patients diagnosed as having lymphoma who presented with severe liver dysfunction and received intravenous mechlorethamine between September 1988 and February 2003 at the Mayo Clinic in Rochester, Minn. RESULTS: Forty-one patients were identified, 33 (80%) of whom had newly diagnosed, previously untreated lymphoma. Thirty-seven (90%) had non-Hodgkin lymphoma, and 4 (10%) had Hodgkin disease. Thirty-four patients (83%) had stage IV disease, and 31 (84%) of 37 had an intermediate-high International Prognostic Index. The median total bilirubin level before therapy was 10.7 mg/dL (range, 2.5-30.2 mg/dL), and the median alkaline phosphatase level was 982 U/L (range, 233-3415 U/L). In addition to mechlorethamine, 34 patients (83%) received concomitant corticosteroids, and 12 (29%) received concomitant rituximab. Twenty-two patients (54%) had sufficient improvement in liver function to receive subsequent standard chemotherapy. Nine patients (22%) are alive and disease-free at a median of 31 months (range, 4 to > or = 87 months) after mechlorethamine treatment. Factors associated with improved overall survival included improvement in bilirubin levels (P < .001) and receiving subsequent standard chemotherapy (P = .001). CONCLUSION: Mechlorethamine, high-dose corticosteroids, and rituximab are useful therapeutic interventions for this unique group of patients with lymphoma and severe liver dysfunction. Substantial clinical improvement and long-term survival are possible.

Adrenal Cortex Hormones↗

PubMed2003

Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma.

In this article, we report on 904 patients undergoing transplantation for follicular lymphoma. A total of 176 (19%) received allogeneic, 131 (14%) received purged autologous, and 597 (67%) received unpurged autologous transplants. Five-year treatment-related mortality (TRM) rates were 30%, 14%, and 8% and 5-year recurrence rates were 21%, 43%, and 58% after allotransplantation, purged autotransplantation, and unpurged autotransplantation, respectively. In multivariate analyses, allotransplantation had higher TRM and lower disease recurrence. Purged autotransplantation had a 26% lower recurrence risk than unpurged autotransplantation. Five-year probabilities of survival were 51%, 62%, and 55% after allogeneic, purged autotransplantation, and unpurged autotransplantation, respectively. Advanced age, prolonged interval from diagnosis to transplantation, high lactate dehydrogenase (LDH), refractory disease, bone marrow involvement, low performance scores, and transplantation between 1990 and 1993 were associated with adverse outcomes. Total body irradiation was associated with higher TRM but lower recurrence. There was no association between acute or chronic graft-versus-host disease and recurrence after allotransplantation. We conclude that both allogeneic and autologous transplantation can induce durable remissions. There may be a benefit to graft purging in autologous transplantation. The decreased recurrence after allotransplantation is offset by increased TRM. We did not detect a correlation between graft-versus-host disease (GVHD) and recurrence. Finally, outcomes of transplantation for follicular lymphoma show improvement over the past decade.

Adult↗