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D J Inwards

Publications and source records attributed to D J Inwards.

At least 37 records · Page 2Linked to original sources

Testicular lymphoma is associated with a high incidence of extranodal recurrence.

BACKGROUND: Testicular lymphoma is a rare extranodal presentation of non-Hodgkin lymphoma. The authors report long term follow-up information regarding a group of patients with testicular lymphoma evaluated at the Mayo Clinic and describe the outcome with special attention to patterns of recurrence. METHODS: The medical records of patients with testicular lymphoma seen at the Mayo Clinic between January 1970 and March 1993 were reviewed. Patients were included if they had evidence of testicular involvement at the time of diagnosis of lymphoma. Pathology specimens were reviewed for confirmation of diagnosis. RESULTS: Sixty-two patients with a diagnosis of testicular lymphoma were identified. Their median age was 68 years, and 60 patients underwent orchiectomy as the initial therapeutic and diagnostic procedure. Most of patients (79%) had localized or regional disease at the time of presentation. Other treatment modalities after diagnosis included radiotherapy (37%), combination chemotherapy (37%), and combination chemotherapy and radiotherapy (16%). Although 88% of patients had no residual disease after primary treatment, 80% subsequently experienced disease recurrence. There was no significant difference in the rate of recurrence, including Ann Arbor Stage I disease. Treatment did not appear to affect the recurrence rate. At a median follow-up of 2.7 years, 60% of patients had died of disease. Late recurrences were observed, and there appeared to be no plateau in the disease free survival curve. In half (51%) of the patients with disease recurrence, only extranodal locations were involved. Thirteen patients experienced recurrence in the central nervous system, 11 of whom had parenchymal lesions. In 8 of these 13 patients, the central nervous system was an isolated site of disease recurrence. CONCLUSIONS: Testicular lymphoma is a unique and aggressive extranodal non-Hodgkin lymphoma. Better treatment strategies are needed to prevent recurrences. The risk of extranodal recurrence is high, especially in the central nervous system.

Adult↗

Delayed stem cell transplantation for the management of relapsed or refractory multiple myeloma.

The optimal timing of stem cell transplantation for multiple myeloma is controversial. Late stem cell collection is undesirable because of the inability to mobilize stem cells. We report on 64 recipients of stem cells collected within 1 year after diagnosis, none of whom had transplantation in plateau phase of their disease. Patients seen within 12 months after diagnosis received four cycles of standard vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy and then had stem cells mobilized. Patients were then placed on maintenance vincristine, BCNU, melphalan, cyclophosphamide, and prednisone or melphalan and prednisone chemotherapy for 12 cycles. At the sign of first progression, transplantation occurred. Fourteen patients were refractory to VAD chemotherapy, 20 relapsed on maintenance chemotherapy, and 30 relapsed off chemotherapy. The time to platelet engraftment was not affected by the duration of stem cell cryopreservation or extent of chemotherapy exposure after mobilization. The complete response rate was 34%. The actuarial median survival from initial diagnosis, from transplant day 0, and post-transplant progression-free survival was 51, 20 and 11.4 months, respectively. The patient status at transplantation and percentage of plasma cells circulating in the blood at apheresis influenced post-transplant survival; circulating plasma cells, status at transplantation and plasma cell labeling index influenced progression-free survival. Response duration was shorter in patients relapsing on chemotherapy.

Adult↗

Blood stem cell transplantation as therapy for primary systemic amyloidosis (AL).

This study investigated the response rate and toxicity of blood cell transplantation as treatment for primary amyloidosis (AL). Twenty-three patients had stem cells collected between November 1995 and September 1998. Conditioning included melphalan and total body irradiation in 16 and melphalan alone in 4. Three patients did not undergo stem cell infusion because of poor performance status. Two died of progressive amyloid at 1 and 3 months. One patient is alive on hemodialysis. Fourteen males and six females (median age, 57 years) underwent transplantation. Renal, cardiac (by echocardiography), peripheral neuropathy or liver amyloidosis occurred in 14, 12, 3, and 1, respectively. Echocardiography demonstrated an interventricular septal thickness > or = 15 mm in six patients, five of whom died post transplantation. Three patients died of progressive amyloidosis at 7, 7, and 21 months. Thirteen patients are alive with a follow-up of 3 to 26 months. Twelve (60%) fulfilled the criteria of a hematologic or organ response. Severe gastrointestinal tract toxicity was seen in five (25%). We conclude that blood cell transplantation for amyloidosis had a much higher morbidity and mortality compared with transplantation for myeloma. The best results appear to occur in patients with nephrotic syndrome as the only manifestation of their disease.

Adult↗

A randomized, placebo-controlled study of outpatient premedication for bone marrow biopsy in adults with lymphoma.

The outpatient bone marrow biopsy and aspiration (BMBA) procedure performed with local anesthetic is often poorly tolerated in adults. This prospective, randomized, placebo-controlled, double-blind trial was designed to determine whether oral (p.o.) lorazepam and hydromorphone reduces pain and anxiety during BMBA. Eligible patients had lymphoma, had no prior BMBA, and were > or = 18 years old. Since patients had bilateral BMBA, each served as their own control. Patients were stratified by anxiety level using the Spielberger Trait Anxiety Scale and randomized to: A) placebo for the first BMBA and 2 mg lorazepam and 2 mg hydromorphone p.o. for the contralateral BMBA, or B) placebo for both BMBAS. Changes in pain and anxiety experienced between the first and second BMBA were measured by the Visual Analogue Scale (VAS) and the Spielberger State Anxiety Scale at the time of the BMBA and 24 hours later. Twenty-seven patients were enrolled and 25 were evaluable; there were 17 males and eight females. The median age was 57 years (range, 28-79 years). Overall, BMBA was reported as painful in both arms, with a median VAS pain score after the second BMBA of 3.9 (scale, 0-10) for arm A and 5.8 for arm B (P = 0.21). There was no difference in the change in pain, anxiety, or recalled anxiety between treatment arms (all P values > 0.05). The difference in the change in recalled pain was of borderline significance (P = 0.07) and consistent with benzodiazepine-induced anterograde amnesia.

Administration, Oral↗

Early harvest and late transplantation as an effective therapeutic strategy in multiple myeloma.

Transplantation after high-dose chemotherapy prolongs survival in patients with multiple myeloma compared with standard therapy. It is unclear whether the optimal timing of transplantation is immediately after induction chemotherapy or whether stem cells may be cryopreserved for transplantation at subsequent progression or relapse. In this study, stem cells were collected within 6 months of diagnosis, followed by transplantation only at progression of myeloma. One hundred and eighteen patients with multiple myeloma had stem cells collected and cryopreserved. Eleven had transplants early in the disease after they demonstrated failure to respond to primary therapy. The remaining 107 were eligible for transplants when there was evidence of progressive disease. Of the 118 patients, 67 had transplants, nine died of progressive disease before transplantation, and 42 remain alive in plateau phase. The median survival of the group is 58.5 months; 67 are alive. Serum beta2-microglobulin, bone marrow labeling index (S phase), and hemoglobin level predicted overall survival (P < 0.006, P < 0.001, and P < 0.01, respectively). We conclude that early cryopreservation of blood stem cells followed by transplantation at progression is a feasible approach to therapy in patients with myeloma. The underlying biology of the disease has a greater impact on survival than the timing of transplantation. A prospective randomized trial is required to answer definitively the question of the optimal timing of blood cell transplantation.

Adult↗

Detection of t(2;5) in anaplastic large cell lymphoma: comparison of immunohistochemical studies, FISH, and RT-PCR in paraffin-embedded tissue.

Anaplastic large cell lymphoma (ALCL) is associated with the t(2;5)(p23;q35) translocation involving the anaplastic lymphoma kinase gene (ALK) and the nucleophosmin gene (NPM), which result in expression of a novel fusion protein, NPM-ALK (p80). Clinicopathologic studies have shown that ALK expression in ALCL is associated with improved 5-year survival rates when compared with ALCL lacking ALK expression. This study used paraffin-embedded tissue to compare interphase fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of t(2;5) with immunohistochemical analysis for the detection of ALK protein expression in 27 patients with CD30-positive ALCLs. ALK protein expression was detected with ALK1 antibody in 14 of the 27 patients. The neoplastic cells in 13 of these 14 lymphomas reacted with the p80NPM/ALK antibody. FISH, using a two-color ALK DNA probe, correlated 100% with the immunohistochemical results: a translocation involving the ALK gene was detected in all 14 lymphomas that reacted with anti-ALK1. RT-PCR, performed on 21 lymphomas, detected NPM-ALK mRNA in five of the lymphomas, all of which reacted with anti-ALK1 and showed ALK gene rearrangement by FISH. Lymphomas showing ALK1 reactivity occurred in a younger patient population (median age, 19.5 years) and were associated with improved 5-year survival rates (84%), as compared with lymphomas lacking ALK1 reactivity (median age, 68.0 years; 5-year survival rate, 35%; p = 0.008). We conclude that immunohistochemical studies, using antibody ALK1. and FISH for ALK gene rearrangement are equally effective for identifying patients with ALCL who have a favorable clinical outcome.

Adolescent↗

Spontaneous remission of anemia associated with a myelodysplastic syndrome with disease evolution into a myeloproliferative state.

A red cell transfusion-dependent patient with a myelodysplastic syndrome had progression into a myeloproliferative state with thrombocytosis. At the same time, the patient became transfusion independent, and a subsequent bone marrow examination revealed a previously undetected loss of chromosome 7. The patient remains well with control of thrombocytosis by anagrelide therapy.

Anemia↗

Primary pulmonary lymphoma.

Lymphoproliferative diseases affecting the lung occur over a broad clinical and pathologic spectrum. The clinical presentations and radiologic findings are nonspecific, entailing broad differential diagnoses. Accurate diagnosis requires adequate tissue sampling with appropriate ancillary pathologic studies. The recent delineation of new pathologic entities such as low-grade malignant lymphoma of mucosa-associated lymphoid tissue (MALT type) has aided in the understanding of the pathophysiology, clinical course, and management of patients with pulmonary lymphoma. Significant observations have been made in the clinical management and treatment of these disorders.

Antineoplastic Combined Chemotherapy Protocols↗

Late-onset noninfectious pulmonary complications after allogeneic bone marrow transplantation.

We examined the incidence and clinical outcome of late-onset noninfectious pulmonary complications (LONIPC) in a series of 234 patients who underwent allogeneic bone marrow transplantation at our institution between April 1982 and October 1996. The 179 patients who survived 3 months or more were evaluated. Clinical, radiologic, pulmonary function, and pathologic tests were reviewed to identify 18 patients (10%) who fulfilled the diagnostic criteria of LONIPC. Accordingly, the pulmonary processes included bronchiolitis obliterans (BO, five patients), bronchiolitis obliterans with organizing pneumonia (BOOP, three patients), diffuse alveolar damage (DAD, one patient), lymphocytic interstitial pneumonia (LIP, one patient), and nonclassifiable interstitial pneumonia (NCIP, eight patients). Various methods of enhanced immunosuppressive therapy resulted in marked durable remission in nine patients (50%) (3/3 with BOOP, 3/8 with NCIP, 1/1 with DAD, 1/1 with LIP, 1/5 with BO). The presence of chronic graft-versus-host disease (cGVHD) and prophylaxis for GVHD with cyclosporine and prednisone were the only variables significantly associated with the development of LONIPC (P = 0.0001 and 0.008, respectively). Regardless of histology, a reduction in the forced expiratory volume to < 45% of the predicted range was associated with poor response to treatment. These findings suggest a strong association between cGVHD and LONIPC and that the risk of LONIPC development may be influenced by the particular method of GVHD prophylaxis. Most patients with BOOP or mild airflow limitation at diagnosis achieved durable remissions.

Adolescent↗

Multiple myeloma associated with diffuse osteosclerotic bone lesions: a clinical entity distinct from osteosclerotic myeloma (POEMS syndrome).

Multiple myeloma usually is characterized by the development of lytic bone lesions. Osteosclerotic myeloma is a rare entity characterized by a single or multiple osteosclerotic bone lesions and often accompanied by a demyelinating polyneuropathy. Multiple myeloma associated with widespread osteosclerotic lesions seen on radiographic studies is exceedingly rare. We describe 3 such cases and review 12 other cases described in the literature. Overall, the patients described herein had a clinical course that resembled multiple myeloma more than osteosclerotic myeloma. However, some patients had features of both diseases. Although rare, multiple myeloma should be included in the differential diagnosis of widespread osteosclerotic bone lesions.

Bone and Bones↗

Factors influencing platelet recovery after blood cell transplantation in multiple myeloma.

We sought to determine factors that impact on the recovery of platelets after blood cell transplantation in patients with multiple myeloma. We performed retrospective analyses in 51 patients undergoing blood cell transplantation for multiple myeloma. The proportional-hazards model was applied to determine significant risk factors. Of 51 transplants, 14 patients failed to achieve a platelet count of 50 x 10(9)/l. Median time to a neutrophil count of 0.5 x 10(9)/l was 10.5 days. Median time to achieve a platelet count of 50 x 10(9)/l was 32 days. Multivariate analysis revealed that cyclophosphamide and G-CSF priming before collection of hematopoietic precursors (P < 0.001) was a positive predictor of rapid engraftment and prior exposure to melphalan given orally (P = 0.02) was a negative predictor of subsequent platelet engraftment. The number of mononuclear cells collected, the patient's disease status at the time of transplant and the presence of circulating plasma cells in the harvested product did not have a significant impact on time to platelet engraftment. We conclude that cyclophosphamide and G-CSF priming shortened the time to achieve platelet engraftment compared with G-CSF alone. Prior exposure to melphalan delayed platelet engraftment and can lead to complete failure of platelet recovery. Stem cells should be collected before melphalan administration in patients with multiple myeloma who are candidates for possible blood cell transplantation.

Adult↗

Malignant lymphoma of the bladder: evidence from 36 cases that low-grade lymphoma of the MALT-type is the most common primary bladder lymphoma.

Patients with malignant lymphoma of the bladder were studied, and three clinical groups were defined: those with primary lymphoma localized in the bladder, lymphoma presenting in the bladder as the first sign of disseminated disease (nonlocalized lymphoma), and recurrent bladder involvement by lymphoma in patients with a history of malignant lymphoma (secondary lymphoma). The differences in these groups regarding lymphoma type, clinical presentation, and clinical outcome were studied. Mayo Clinic Tissue Registry records from 1940 to 1996 were searched to identify patients with lymphomas involving the bladder. The lymphomas were classified based on review of the histology and immunophenotype performed by immunoperoxidase methods. Clinical records were reviewed. Presenting symptoms included urinary frequency, dysuria, hematuria, and lower abdominal and back pain. Primary lymphoma was present in six patients. All were B-cell lineage low-grade lymphomas of the mucosa-associated lymphoid tissue (MALT) type. No patient had recurrent lymphoma or died of lymphoma. Nonlocalized bladder lymphoma occurred in 17 patients; one with low-grade lymphoma of the MALT type, four with follicle center lymphomas, and 12 with large cell lymphomas. Excluding two patients who died postoperatively, median survival was 9 years. Six patients died of lymphoma in the follow-up period. Secondary bladder lymphoma occurred in 13 patients: two with low-grade lymphoma of the MALT type, one with follicle center lymphoma, one with mantle cell lymphoma, and nine with diffuse large cell lymphomas. Median survival in this group was 0.6 years. Low-grade lymphoma of the MALT type was the most frequent type of primary bladder lymphoma and was associated with an excellent prognosis. The bladder can be the presenting site of lymphomatous involvement in patients with more widespread disease. Survival in this group is quite favorable and is presumably dependent on lymphoma histologic type, stage of disease, and other prognostic factors. Bladder involvement by recurrent lymphoma is a sign of widely disseminated disease and is associated with a very poor prognosis.

Adult↗

Predictive capacity of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma.

PURPOSE: The International Prognostic Factor Index has been shown to predict the outcome of patients with predominantly B-cell lymphomas classified using traditional classifications, including the Working Formulation, but its prognostic importance has not been tested in a cohort of patients with exclusively T-cell lymphomas. This study was conducted to evaluate the prognostic significance of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Seventy-eight patients (48 men and 30 women) with PTCL seen at a single institution between 1985 and 1995 were included in the analysis. The morphology and immunocytochemistry of all the original biopsy specimens were reviewed by a single pathologist and classified using the Revised European-American Lymphoma (REAL) classification. The International Prognostic Factor Index, as well as clinical and biochemical parameters, were evaluated by univariate and multivariate analyses to determine their association with patient outcome. RESULTS: The International Prognostic Factor Index strongly predicted survival when all patients were included in the analysis (P < .001). For patients < or = 60 years, the age-adjusted International Index significantly predicted long-term survival (P = .0218). For patients older than 60 years, the age-adjusted International Index also significantly predicted survival (P = .002). Liver involvement (P = .006) and bone marrow involvement (P = .014) were also significant prognostic factors in the univariate analysis, but only the International Index remained significant in the multivariate analysis (P = .001). CONCLUSION: The International Prognostic Factor Index, which significantly predicts outcome in patients with aggressive/intermediate-grade B-cell lymphomas, has similar prognostic importance in patients with PTCL.

Adolescent↗

Refractory and relapsing multiple myeloma treated by blood stem cell transplantation.

Between June 1989 and June 1992, 12 patients with advanced multiple myeloma underwent peripheral blood stem cell autotransplantation after high-dose chemotherapy and radiotherapy. The conditioning regimen included melphalan (140 mg/m2), high-dose cyclophosphamide (120 mg/kg), methylprednisolone (2 g daily x 7), and total body irradiation (9-12 Gy). Transplant morbidity included severe mucositis (n = 7) and acute renal failure (n = 2) related to infusion of the stem cells. Engraftment was delayed (n = 4) in this heavily pretreated population, and two patients had complete graft failure. Despite the advanced nature and chemotherapy-refractory state of their disease, 11 of 11 evaluable patients achieved an objective response. Six patients survived to leave the hospital, and four remain alive--one died of acute leukemia induced by prior melphalan exposure. Three of the four are relapse-free at a median of 24.9 months (range, 18-28 months). Some patients with advanced refractory multiple myeloma can achieve objective responses from highdose chemoradiotherapy with peripheral blood stem cell rescue. Harvesting peripheral blood stem cells from high-risk patients early in their disease for later use may decrease the risk of graft failure. Peripheral blood stem cell transplantation after high-dose chemotherapy and total body irradiation can produce durable responses in patients with advanced refractory myeloma.

Acute Kidney Injury↗

Successful treatment of simultaneous pulmonary Pseudallescheria boydii and Aspergillus terreus infection with oral itraconazole.

Pseudallescheria boydii and Aspergillus terreus are unusual opportunistic fungal pathogens that are often resistant to chemotherapy with amphotericin B. We report a case of simultaneous invasive pulmonary infection with these organisms occurring in a bone marrow transplant recipient who was successfully treated with the oral azole itraconazole.

Administration, Oral↗