Anne Kessinger

Non-small cell lung cancer.

Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.

Small Cell Lung Cancer

Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.

High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin's lymphoma.

PURPOSE To evaluate clinical and tumor characteristics in patients receiving high-dose chemotherapy and autologous peripheral stem-cell transplantation (PSCT) or bone marrow transplantation (ABMT) for relapsed or primary refractory non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS One hundred fifty-eight patients with NHL received high-dose chemotherapy and ABMT or PSCT. A multivariate analysis of characteristics was performed for comparison of the long-term failure-free survival (FFS) rate. RESULTS Using a multivariate analysis, a prognostic model was constructed with patients in the good-prognosis group being those without a mass > or = 10 cm at the time of transplant, and no more than one of the following characteristics: three or more prior chemotherapy regimens, lactate dehydrogenase (LDH) level above normal, and chemotherapy resistance. Patients in the poor-prognosis group had a mass > or = 10 cm, or two of the other characteristics noted. The poor-prognosis group had a 3-year FFS rate of 10%, compared with a 45% 3-year FFS in the good-prognosis group (P < .001). Within the prognostic groups, there was no difference in the 3-year FFS rate of the poor-prognosis patients who received ABMT versus PSCT (10% v 12%; not significant). However, in the good-prognosis group, patients who received ABMT had a 3-year FFS rate of 32%, compared with 70% for those who received PSCT (P < .008). CONCLUSION This prognostic model can identify patients with good and poor prognoses following high-dose chemotherapy and ABMT or PSCT for aggressive NHL. In good-prognosis patients, those who received PSCT had a superior FFS rate.

Diffuse alveolar hemorrhage in autologous bone marrow transplant recipients.

PURPOSE The purpose of our work was to evaluate pulmonary complications in autologous bone marrow transplant recipients. PATIENTS AND METHODS A total of 141 consecutive autologous bone marrow transplant recipients were evaluated. In 29 patients, a clinical syndrome characterized by progressive dyspnea, hypoxia, cough, diffuse consolidation on chest roentgenography, and characteristic bronchoalveolar lavage findings developed over one to seven days. RESULTS In 29 patients, bronchoalveolar lavage performed by sequential instillation and aspiration of 20-ml aliquots of normal saline resulted in recovered lavage fluid that became progressively bloodier with each recovered aliquot. Autopsy and bronchoalveolar lavage in these patients revealed no pathogens that accounted for the clinical findings. Since the later aliquots sample predominantly alveolar material, this syndrome was termed diffuse alveolar hemorrhage (DAH). DAH was associated with a high inpatient mortality rate (23 of 29 died versus 14 of 112 without DAH, p less than 0.001) and was associated with age over 40 years, solid malignancies, high fevers, severe mucositis, white blood cell recovery, and renal insufficiency (p less than 0.05, compared with patients without DAH). However, DAH was not associated with prolonged prothrombin or partial thromboplastin times or decreased platelet counts compared with patients without DAH. CONCLUSION DAH is a frequent cause of respiratory compromise and a major cause of mortality in autologous bone marrow transplant recipients.

Autologous bone marrow transplantation for patients with relapsed hodgkin's disease

PURPOSE High-dose therapy and autologous bone marrow transplantation (ABMT) are being increasingly utilized for the management of patients with relapsed Hodgkins disease. Because patients with relapsed Hodgkins disease often initially respond to salvage chemotherapy regimens, ABMT is frequently delayed until late in the course of the disease. The optimal timing for ABMT has not been identified. The purpose of this study was to determine the value of ABMT earlier in the course of Hodgkins disease. PATIENTS AND METHODS We treated 70 patients between October 1984 and October 1988 with high-dose cyclophosphamide, carmustine, and etoposide, followed by infusion of previously cryopreserved autologous bone marrow, and analyzed the results to determine the impact of timing of ABMT on treatment outcome. One (17 patients), two (24 patients), or three or more (29 patients) chemotherapy regimens had failed in patients before ABMT. RESULTS The results for all 70 patients included a complete remission rate of 59%, an early death rate of 11%, a 4-year survival of 47%, and 27% of all treated patients alive and in complete remission at 4 years. The median follow-up for patients remaining in complete remission is 56 months (range 26 to 73 months). The frequency of achieving a complete remission was higher in patients in whom fewer regimens had failed before ABMT (i.e., 82% versus 58% versus 45%, p = 0.02), as was the 4-year disease-free survival (i.e., 44% versus 33% versus 21%, p = 0.04). CONCLUSION ABMT is a more effective therapy when used early for patients with relapsed Hodgkins disease.

NOSOCOMIAL INVASIVE ASPERGILLOSIS IN LYMPHOMA PATIENTS TREATED WITH BONE MARROW OR PERIPHERAL STEM CELL TRANSPLANTS

OBJECTIVES To determine the prevalence of aspergillosis in lymphoma patients housed in a protective environment while undergoing a bone marrow transplant or peripheral stem cell transplant and its relation to lymphoma type, type of transplant, period of neutropenia, method of diagnosis, species of Aspergillus, and the use of empiric amphotericin B. DESIGN Clinical, autopsy, and microbiology records were reviewed retrospectively to determine the presence or absence of invasive aspergillosis. All positive specimens underwent further review to determine parameters outlined above. SETTING The review took place at the University of Nebraska Medical Center with lymphoma patients housed in the oncology/hematology special care unit, which consists of 30 single-patient rooms under positive pressure with high-efficiency particulate air filtration. PATIENTS 417 lymphoma patients admitted to the oncology/hematology special care unit who underwent 427 courses of high-dose chemotherapy with or without total body irradiation followed by a stem cell rescue. RESULTS Twenty-two cases (5.2%) of nosocomial invasive aspergillosis (14 caused by Aspergillus flavus, 2 by Aspergillus terreus, 2 by Aspergillus fumigatus, and 4 by characteristic histology) were diagnosed. The prevalence of disease according to transplant was 8.7% for allogeneic bone marrow transplant (2/23 treatments), 5.6% for autologous peripheral stem cell transplant (9/161), and 4.5% for autologous bone marrow transplant (11/243). Fifteen patients were presumptively diagnosed prior to death (68.2%) most commonly by histologic examination of skin biopsies. All 22 patients received amphotericin B therapy, 17 prior to aspergillosis diagnosis, and 7 (31.8%) survived. No patient with disseminated disease survived. CONCLUSIONS Even when housing lymphoma patients undergoing myeloablative therapy in a protective environment containing high-efficiency particulate air filtration, there was a risk of developing aspergillosis. These data also showed that antemortem diagnosis with aggressive amphotericin B therapy was most effective in the management of infected lymphoma patients when engraftment occurred and the disease did not become disseminated.

Mesna compared with continuous bladder irrigation as uroprotection during high-dose chemotherapy and transplantation: a randomized trial.

PURPOSE To compare the use of intravenous (IV) hydration plus either continuous bladder irrigation or mesna for the prevention of hemorrhagic cystitis in the bone marrow transplant setting. PATIENTS AND METHODS Two hundred patients were prospectively randomized to receive either continuous bladder irrigation with 200 mL/h of normal saline, or continuous infusion mesna at 100% of the cyclophosphamide dose. RESULTS The overall incidence of hematuria of any grade was significantly higher in the bladder-irrigation group (76%) compared with the mesna group (53%) (P = .007). However, the incidence of grade III and IV hematuria was the same in both groups (18%; P = NS). Moderate or severe discomfort or bladder spasms were reported in 84% of the patients who received bladder irrigation, compared with 2% of the patients who received mesna prophylaxis (P < .0001). Urinary tract infections (UTIs) were documented in 27% of the patients in the bladder-irrigation group, compared with 14% of the patients in the mesna group (P = .03). CONCLUSION Both continuous bladder irrigation and mesna were equally effective in preventing severe hemorrhagic cystitis associated with high-dose cyclophosphamide and bone marrow transplantation. However, the use of mesna was associated with significantly less discomfort and a lower incidence of UTIs.

Single-photon emission computed tomography gallium imaging versus computed tomography: predictive value in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin's lymphoma.

PURPOSE To evaluate the predictive value of computed tomography (CT) scanning and single-photon emission computed tomography (SPECT) gallium (Ga) scanning in the disease-free survival of patients receiving high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS One hundred forty-three patients undergoing transplant for NHL underwent CT scanning of chest, abdomen, and pelvis, and a SPECT Ga scan before transplantation and at day + 100 after transplant. The failure-free survival (FFS) by scan result was analyzed. RESULTS In the diffuse aggressive lymphoma patients, the 1-year FFS for patients having a positive SPECT Ga scan at day + 100 was 15% compared with a 3-year FFS of 47% for those with a negative scan (P < .001). Patients with a positive CT scan at day + 100 had a 36% 3-year FFS, and those with a negative CT scan had a 39% 3-year FFS (P = not significant [NS]). An analysis of the combination of CT scan and SPECT Ga scan results at day + 100 posttransplant demonstrated a 3-year FFS of 14% if they were both abnormal; if the CT was positive and Ga was negative, the 3-year FFS was 68%; positive Ga with a negative CT was 25%; and both negative was 34% (P = .0015). For the patients with follicular NHL, those with a positive SPECT Ga at day + 100 had a 14% 1-year FFS compared with those with a negative scan, who had a 45% 3-year FFS (P < .001). In the follicular NHL patients, the 3-year FFS of those with a positive CT was 17% compared with a 64% 3-year FFS for patients with a negative CT scan (P < .001). CONCLUSION The use of SPECT Ga scan at day + 100 posttransplant for evaluation of disease activity in patients with diffuse aggressive NHL was highly predictive of eventual outcome and was more predictive than the CT scan results. However, for patients with follicular NHL, the addition of SPECT Ga scanning to CT scanning did not add substantially to the evaluation of transplant outcome.

Allogeneic-blood stem-cell collection following mobilization with low-dose granulocyte colony-stimulating factor.

PURPOSE The optimal dose of granulocyte colony-stimulating factor (G-CSF) for mobilization of allogeneic-blood stem cells (AlloBSC) has yet to be determined. As part of a prospective trial, 41 related human leukocyte antigen (HLA)-matched donors had blood cells mobilized with G-CSF at 5 micrograms/kg/d by subcutaneous administration. The purpose of this trial was to monitor adverse effects during G-CSF administration and stem-cell collection, to determine the optimal timing for stem-cell collection, and to determine the cellular composition of stem-cell products following G-CSF administration. PATIENTS AND METHODS The median donor age was 42 years. Apheresis began on day 4 of G-CSF administration. At least three daily 12-L apheresis collections were performed on each donor. A minimum of 1.0 x 10(6) CD34+ cells/kg (recipient weight) and 8.0 x 10(8) mononuclear cells/kg were collected from each donor. All collections were cryopreserved in 5% dimethyl sulfoxide and 6% hydroxyethyl starch. RESULTS Toxicities associated with G-CSF administration and the apheresis process included myalgias/arthralgias (83%), headache (44%), fever (27%), and chills (22%). The median baseline platelet count of 242 x 10(4)/ mL decreased to 221, 155, and 119 x 10(6)/mL on days 4, 5, and 6 of G-CSF administration, respectively. Median numbers of CD34+ cells in collections 1, 2, and 3 were 1.99, 2.52, and 3.13 x 10(6)/kg, respectively. The percentage and total number of CD4+, CD8+, and CD56+/CD3- cells remained relatively constant during the three collections. Median total numbers of cells were as follows: CD34+, 7.73 x 10(6)/kg; and lymphocytes, 6.93 x 10(8)/kg. CONCLUSION Relatively low doses of G-CSF can mobilize sufficient numbers of AlloBSC safely and efficiently.

Filgrastim as an Alternative to Donor Leukocyte Infusion for Relapse After Allogeneic Stem-Cell Transplantation

PURPOSE Donor leukocyte infusion (DLI) effectively treats relapse after allogeneic stem-cell transplantation (alloSCT), but the response may require several months and may be associated with significant toxicity. Filgrastim has also been observed to effectively treat leukemic relapse after alloSCT. A retrospective analysis was performed to determine the effectiveness of filgrastim in treating relapses after alloSCT. PATIENTS AND METHODS Fourteen patients with hematologic malignancies were treated with filgrastim at relapse after alloSCT. Filgrastim was given at 5 mcg/kg/d subcutaneously for 21 consecutive days. Response was evaluated at 7 days after completion of filgrastim. Immunosuppressants, if present, were rapidly tapered to complete discontinuation at the time of relapse. RESULTS Three patients were not assessable for response because additional therapy was necessary before completion of filgrastim. Six patients (43%) achieved a complete response on an intent-to-treat basis. When response was evaluated based on relapse type, three of four cytogenetic relapses, two of three morphologic relapses, and one of four hematologic relapses achieved a complete remission. Two responses were observed in patients who were completely off of any immunosuppression at the time of relapse. Six patients developed chronic graft-versus-host disease. The event-free and overall survival rates for all 14 patients are 43% and 73%, respectively. CONCLUSION The use of filgrastim with rapid discontinuation of immunosuppression results in response rates that are similar to results using DLI. Filgrastim could be considered as an alternative or an adjunct to DLI for relapses after alloSCT.