Joseph Aisner

Treatment of invasive aspergillosis: relation of early diagnosis and treatment to response.

Aspergillus infections in patients with cancer are difficult to diagnose, and such diagnoses are frequently made at necropsy. Earlier therapy has been proposed to provide better response. We reviewed 17 consecutive patients with documented aspergillosis to determine the impact of earlier diagnosis and prompt treatment with amphotericin B. Sixteen had hematologic malignancies, and all had marked granulocytopenia. Six were diagnosed and treated within 96 h of the appearance of infiltrates. Three of these six had complete resolution of all signs and symptoms of aspergillus infection. The other three had a partial response to therapy despite continued granulocytopenia. All 11 patients in whom antifungal therapy was either delayed (six) or not given (five) for at least 2 weeks after the infiltrate was present diet with progressive aspergillosis aggressive diagnostic methods to establish the diagnosis of aspergillosis are warranted so that antifungal therapy can be started early, which may then be successful in resolving these potentially fatal infections.

Frozen autologous platelet transfusion for patients with leukemia.

Platelets were removed from 25 patients with leukemia during remission and were frozen for subsequent transfusion. With 5 per cent dimethyl sulfoxide as a cryoprotective agent, we froze 3 to 5 units of pooled platelet concentrate by simply placing the platelets in the vapor phase of a liquid nitrogen freezer. Ninety-one transfusions of platelets stored for 13 to 400 days were administered. The mean freeze-thaw loss was 13 percent, and the corrected one-hour increment in platelet count was 13,700 per microliter, corresponding to a recovery of 53 per cent of the predicted value. In many patients most or all of the transfusion requirements were met with frozen platelets. Our results indicate that frozen platelets can circulate and function hemostatically. Autologous frozen platelets are of particular value in the management of alloimmunized patients and have become an integral part of our transfusion support program.

Torulopsis glabrata infections in patients with cancer: Increasing incidence and relationship to colonization

Torulopsis glabrata, an opportunistic pathogen, was found to be the etiologic agent of infections in patients with cancer. This observation prompted a retrospective review to determine the incidence and underlying factors of infection with this organism. This study showed that T. glabrata had been cultured frequently and that the incidence of infection has been progressively increasing. During a 48-month period (9/70-8/74), T. glabrata was cultured from routine surveillance and diagnostic cultures in 167 patients, 27 of whom had either presumed or documented infection. Review of clinical and necropsy records implicated T. glabrata infections as a contributory factor in the death of 14 of the 27 patients. Etiologic diagnosis of infection was established antemortem in only three patients. Pulmonary isolation in pure growth occurred in 24 of the 27 patients. Seventeen of 19 infected patients who had prior routine surveillance cultures were colonized prior to infection. Infection occurred in the setting of far advanced malignancy or leukopenia and followed the use of systemic, broad spectrum antibiotics. T. glabrata is a frequently overlooked opportunistic pathogen which, in the proper setting, appears to be producing increasing numbers of infections.

The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck

PURPOSE Unresectable squamous cell carcinomas of the head and neck (SCCHN) continue to pose a significant therapeutic challenge. This report defines the toxicities, efficacy, and prognostic factors associated with the combination of carboplatin (CBDCA), paclitaxel, and once-daily radiation for patients with locally advanced disease. Additionally, the pharmacokinetics of paclitaxel were investigated. METHODS AND MATERIALS From 1993-1998, 62 patients with Stage III-IV SCCHN were treated with 70.2 Gy of RT at 1.8 Gy/fraction/day to the primary site. Weekly chemotherapy was given during RT consisting of paclitaxel (45 mg/m(2)/wk) and CBDCA (100 mg/m(2)/wk). All patients presented with locally advanced disease; 77% had T4 disease and 21% had T3 disease. Fifty-eight percent had N2b-N3 disease. RESULTS Sixty patients were evaluable for response and survival with a median follow-up of 30 months (range 7-70). Ninety-eight percent of patients completed prescribed therapy. One patient died after refusing medical management for pseudomembranous colitis and is scored as a Grade 5 toxicity. Two patients suffered Grade 4 leukopenia. Median number of break days was two. A clinical complete response (CR) at the primary site was obtained in 82%, with a total (primary site and neck) CR rate of 75%. The median survival for the entire cohort is 33 months. Response to therapy and status of the neck at presentation were the only prognostic factors found to influence survival. The median survival for patients who attained a CR is 49 months versus 9 months in those who did not attain a CR (p < 0.0001). The 2- and 3-year overall survival for complete responders are 79% and 61%. Plasma paclitaxel concentrations in the range shown to be radiosensitizing were achieved. CONCLUSIONS Weekly carboplatin and paclitaxel given concurrently with definitive once-daily external beam radiation therapy is well tolerated with over 90% of patients completing prescribed therapy. An ultimate CR rate of greater than 70% was obtained, which translated directly into improved survival. With 48% 3-year overall survival for the entire group, this regimen is an excellent option for this group of patients with a historically poor prognosis.

A comparison of intermittent vs. continuous and of adriamycin vs. methotrexate 5-drug chemotherapy for advanced breast cancer A Cancer and Leukemia Group B study

THE THERAPEUTIC EFFECTIVENESS OF INTERMITTENT vs. continuous combination chemotherapy and of the substitution of adriamycin for methotrexate in a 5-drug regimen was evaluated in women with metastatic breast carcinoma. Patients were randomly allocated to receive continuous therapy with cyclophosphamide, methotrexate, 5-fluo-rouracil, vincristine, prednisone (CMFVP-C, 86 patients), intermittent CMFVP (CMFVP-I, 109 patients), or intermittent CAFVP (107 patients). The CR + PR rate with CAFVP (71%) was superior to CMFVP-C (50%, p = 0.003) and to CMFVP-I (50%, p = 0.002). The remission duration with CAFVP (14 months, median) was superior to CMFVP-I (7 months) (p < 0.01), and tended to be superior to CMFVP-C (9 months) (p = 0.07). There was a survival advantage of CAFVP (19 months, median) over CMFVP-I (13 months) (p = 0.01), but not over CMFVP-C (16 months) (p = 0.24). Among CR + PR patients, the survival with CAFVP (29 months, median) was superior (p = 0.02) to both CMFVP-I (18 months) and CMFVP-C (21 months). The CMFVP-C regimen was associated with the highest incidence of leukopenia and neurologic toxicity, but the lowest incidence of GI toxicity. The results indicate that the CAFVP regimen is well tolerated and is superior to the CMFVP regimens.

Pregnancy outcome in patients treated for Hodgkin's disease.

PURPOSE This study attempted to determine the outcome of pregnancies in patients (or their partners) who were successfully treated for Hodgkins disease and to assess the effect of treatment on the children of the treated parents. MATERIALS AND METHODS A questionnaire was distributed to and personal interviews were conducted with patients who were of reproductive age at the time of treatment with consecutive protocols of radiotherapy, chemotherapy, or both. Those premenopausal patients (or the sexual partners of patients) who attempted to conceive after successful treatment constituted the study population. Fertility assessment was based only on those patients identified as desiring children. RESULTS Among 391 adult patients, 221 patients (104 females and 117 males) of reproductive age were interviewed. Before treatment, 63 of the 221 patients had 135 pregnancies, which resulted in 118 children, 11 spontaneous abortions, five elective abortions, and one stillborn. After treatment, 94 patients (43 females and 51 males) actively attempted conception; 35 females and 25 partners of male patients had 84 pregnancies, which resulted in 68 living children. Among the 84 pregnancies, there were one premature birth at 29 weeks, three spontaneous abortions, 11 elective abortions, and two stillborn: one at 32 weeks and one set of twins. The children have been observed for a median of 11 years (minimum follow up > 4.5 years). Of those patients who desired children, 35 of 43 females became pregnant, whereas only 25 of the 51 partners of male patients became pregnant. At least five male patients with low sperm counts apparently fathered children. CONCLUSIONS This study demonstrates that both men and women have the potential for fertility after treatment regardless of treatment modality. The partners of male patients who were treated with combined modality treatment had a lower frequency of pregnancy than did the female patients who attempted conception and their frequency of pregnancy was also lower than the general population. There was no apparent increase in complications of pregnancy, spontaneous abortions, or congenital abnormalities after treatment compared with pregnancies in this patient group before treatment or with pregnancies in the general population.

Clinical experience with transfusion of cryopreserved platelets.

Summary. Multiple units of platelet concentrate obtained by plateletpheresis of normal, ‘random’or HL‐A matched donors were pooled and frozen in polyolefin bags using 5% dimethylsulphoxide (DMSO) as a cryoprotective agent and a controlled freezing rate of 1°/min. The platelets were stored at approximately — 120° C for as long as 201 days, thawed rapidly at 37°, washed once and resuspended in ACD plasma prior to transfusion. Two different final concentrations of platelets (˜ 2.7 and 9.0 × 1012/1.) were studied. Twenty‐three thrombocytopenic patients have received a total of 40 frozen platelet transfusions. The mean freeze‐thaw loss was 21% and was similar for both platelet concentrations. All transfusions were well tolerated and there were no side effects attributable to the small amounts of DMSO infused. Increments in platelet counts I h after transfusion ranged from 0 to 102 × 109/1. with an overall mean corrected increase in evaluable patients of 12 800 (increase × surface area (m2)/number of platelets transfused × 1011). Corrected increases tended to be greater with the low concentration of platelets. Overall, the increase in count for the frozen platelet transfusions was 65% of the increments obtained with fresh platelet transfusions administered within I week of the frozen platelets. Bleeding times were partially corrected after four out of six transfusions with post‐transfusion counts greater than 50 × 109/1., and active haemorrhage was controlled in some patients by frozen platelet transfusions. These results indicate that pooled platelets can be frozen, thawed and transfused with reasonable efficiency. The frozen platelets can circulate and function haemostatically and may eventually play an important role in supportive care.

Clinical experience with transfusion of granulocytes obtained by continuous flow filtration leukopheresis

Granulocytes obtained by continuous flow filtration leukopheresis (CFFL) were transfused to 21 patients on 131 occasions. An average of 28.2 times 10-9 granulocytes were administered per transfusion. These cells were more than 90 per cent viable by dye exclusion, ingested latex particles normally and had almost normal bactericidal activity. Migration to skin windows was demonstrated on four of six attempts, but 51-Cr-labeling studies failed to show localization in infected areas on six occasions. Post-transfusion granulocyte count increments averaged 225/mul and were transient. Significant transfusion reactions occurred during 35 transfusions to 13 patients. Reactions occurred in some patients without demonstrable alloimmunization and after six infusions of HL-A identical or compatible cells. Definite clinical improvement was noted in three recipients. Stabilization of infection with patient survival occurred nine times, and progression of infection with death eight times. Granulocytes obtained by CFFL are viable and functional. Their transfusion is not without risk and must still be considered an investigative procedure of suggestive but as yet unproved clinical efficacy.

Use of the computed tomographic whole body scanner to stage and follow patients with advanced ovarian carcinoma.

Advanced ovarian carcinoma continues to be a difficult tumor to evaluate noninvasively. Recent developments in chemotherapy have enhanced response rates in this disease, thus improving the likelihood of tumor regression. Computed Tomography (CT) allows the noninvasive estimation of tumor extent in patients with ovarian carcinoma. Seventeen patients with epithelial ovarian carcinoma had 22 whole body CT scans performed either just prior to or following laparotomy. For determination of tumor involvement, when the CT was positive, a high pathologic correlation was found at liver, ascitic, peritoneal, mesenteric, and omental sites (sensitivity). When the cT was negative, high pathologic correlation was found at ascitic and mesenteric sites (specificity). Lower and negative correlation at other disease sites is attributed to difficulty of CT detection of small (1 cm) tumor nodules on visceral surfaces. Eighteen patients with advanced ovarian carcinoma were followed prospectively during treatment with repetitive CT scans. CT results were compared with physical examination, other radiologic studies, and clinical status. In 83% (15/18) of patients and 88% (59/67) of CT scans performed, CT was found to contribute useful management information. Clinical decisions were made on the basis of CT alone in 43% (29/67) of scans performed. These data suggest that CT scanning is very useful in the staging and follow-up of patients with ovarian carcinoma and can replace other radiologic procedures, but it is not completely accurate and needs to be correlated with physical examination and in cases without tumors visible with CT, with laparotomy.

Long-term results of a combined modality approach in treating inflammatory carcinoma of the breast

Twenty-eight patients with inflammatory carcinoma of the breast were managed initially by induction chemotherapy consisting of 3 courses of a combination of cyclophosphamide, doxorubicin hydrochloride, and 5-fluorouracil. Twenty-two showed a partial response, and 21 underwent mastectomies. Histopathologic examination of the surgical specimens revealed no residual tumor in 2 breasts, but all 21 patients had residual metastases in their axillary lymph nodes. Postoperatively, they received the same chemotherapy. The other six patients who failed to respond to induction chemotherapy received radical radiation therapy followed by a combination chemotherapy regimen that consisted of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone. Any patient in whom chemotherapy failed during the follow-up period was treated by radiation therapy and/or a combination of mitomycin-C and vinblastine as necessary. At the time of diagnosis, 17 patients who had no evidence of distant metastasis, i.e., stage III B disease, had disease-free survival ranging from 5 to more than 84 months, with a median of 30 months, and an overall survival of 7 to more than 120 months with a median of 32 months. The 5-year survival rate was 18%. The other 11 patients who had distant metastases, i.e., stage IV disease, had an overall survival ranging from 4 to 14 months. The results of this approach of initial systemic chemotherapy followed by local-regional cytoreductive therapy, then systemic therapy, might suggest some survival benefits in patients with stage III disease.