Phase I dose escalation study of topotecan combined with alternating schedules of paclitaxel and carboplatin in advanced solid tumors.

BACKGROUND: Combining topotecan with other cytotoxics has been problematic due to marrow suppression. A phase I trial was initiated to identify the optimal sequence and maximum-tolerated dose of topotecan in combination with paclitaxel and carboplatin. PATIENTS AND METHODS: Patients with advanced cancer and performance status ECOG < or = 2. The starting dose was paclitaxel 175 mg/m2 day 1, carboplatin AUC 6.0 day 1, and topotecan 0.5 mg/m2 daily day 1-5 (early sequence). The next course of paclitaxel and carboplatin administration was delayed to day 5 (late sequence). Treatment was repeated every three weeks. After determining maximum-tolerated dose without cytokines, granulocyte colony-stimulating factor (G-CSF) was added and further dose escalation was pursued. RESULTS: Fifty-one patients were entered; men: women ratio 30:21. Dose-limiting toxicity (DLT) for the early sequence was neutropenia at doses paclitaxel mg/m2/carboplatin AUC 5/topotecan mg/m2 (PCT) 175/5/0.75 for four to five days. DLT for the late sequence was neutropenia at PCT doses of 175/5/ 1.0 for four days. G-CSF 5 microg/kg subcutaneously starting day 6 permitted further topotecan dose escalation. After adding G-CSF, late sequence DLT was neutropenia at doses 175/5/1.25 for four days. Forty-six patients were evaluable for response and of those, there were thirteen partial responses. CONCLUSIONS: The late sequence resulted in less toxicity and was better tolerated. The early sequence maximum-tolerated dose (MTD) was 175/6/0.5 for five days. The late sequence MTD was PCT 175/5/0.75 for five days. The late sequence MTD with G-CSF was 175/5/1.0 for four days. The recommended phase II PCT dose is the late sequence 175/5/1.0 for four days with G-CSF.

Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 an 1999.

BACKGROUND: After standard therapy for advanced head and neck carcinoma, 5-year survival rate is less than 50%. Our purpose was to develop a new treatment for advanced head and neck carcinoma by using preoperative chemotherapy. Long term efficacy and toxicity of induction paclitaxel and carboplatin is reported here. METHODS: Between 1994 and 1999, 62 consecutive patients with newly diagnosed head and neck carcinoma were treated with paclitaxel and carboplatin induction chemotherapy. Chemotherapy was administered every 21 days with 3 courses of paclitaxel (150-265 mg/m(2)) and carboplatin at a dose calculated using the Calvert formula area under the curve of 7.5. Patients who achieved complete or partial response at the primary received definitive radiation to the primary tumor and those with lymph node disease received neck dissection followed by radiation to the regional lymph nodes. Nonresponders received standard resection of primary tumor and draining lymph node basin followed by radiation. RESULTS: Sixty-two consecutive patients were treated. Seventy-four percent had Stage IV (according to the 5th edition of American Joint Committee on Cancer Staging manual) disease. The median duration of follow-up from initiation of chemotherapy was 64 weeks (range, 1-272 weeks). Overall complete plus partial response rate was 41 of 62 (66%). Responses were observed at all anatomic sites: oropharynx 20 of 33 (61%); hypopharynx 8 of 12 (67%); and larynx 13 of 17 (76%). Kaplan-Meier estimates of overall survival (OS), at 230 weeks, were significantly better in Stage IV oropharynx/hypopharynx responders than nonresponders (55% vs. 27%; P = 0.04). Of the variables evaluated in multivariate models, response at the primary tumor and lymph nodes were associated with improved disease free survival and OS. Organ preservation was achieved in 28 of 62 (45%) of patients at all anatomic sites: oropharynx 39%, hypopharynx 42%, larynx 59%. Seventeen of 28 (61%) patients had their primary organ site preserved for a mean duration of 78 weeks (range, 13-238 weeks). CONCLUSIONS: Induction paclitaxel and carboplatin was well tolerated. The response rate was encouraging considering most patients were Stage IV. Chemotherapy response identified a group with improved prognosis. Organ preservation was possible at all anatomic sites.

Surveillance for recurrent head and neck cancer using positron emission tomography.

PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P =.013) or PE (P =.002) in the detection of recurrence. CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.

Initial evaluation of pulmonary abnormalities: CT-guided fine-needle aspiration biopsy and fluoride-18 fluorodeoxyglucose positron emission tomography correlation.

Fluoride-18 fluorodeoxyglucose positron emission tomography (FDG-PET) can evaluate patients with new pulmonary lesions. CT-guided fine-needle aspiration (FNA) biopsy is a well-described method in the diagnosis of pulmonary lesions. In order to correlate results from these testing modalities, retrospective findings from FNA biopsies of pulmonary lesions are compared to concurrent FDG-PET scans. Files of the Saint Louis University Hospital were retrospectively searched for patients with CT-guided FNA biopsies of the lung during a consecutive 3-yr period. Patients were collected, and corresponding FDG-PET scans were identified. Only new pulmonary lesions presenting for initial evaluation were included. Findings were correlated. Forty patients with a total number of 41 CT-guided FNA biopsies of the lung and thoracic cavity had corresponding FDG-PET scans. The combined positivity of the two testing modalities, i.e., cases where both FNA and FDG-PET scan were positive, yielded a sensitivity of 100% (37/37). Four patients had infectious/inflammatory processes by CT-guided FNA biopsy that were FDG-PET-positive for malignancy. CT-guided FNA biopsies with FDG-PET scans of pulmonary lesions are important, complementary diagnostic tools which can contribute significantly to the management and treatment of pulmonary disease. Diagn. Cytopathol. 2000;22:92-96.

Erythropoietin reduces anemia and transfusions: A randomized trial with or without erythropoietin during chemotherapy.

BACKGROUND: Anemia has been reported to develop during preoperative chemotherapy with paclitaxel and carboplatin. The use of recombinant human erythropoietin (EPO) has been shown to reduce anemia and subsequent packed red blood cell transfusions. The current study is a report of a Phase III, prospective, randomized trial with or without EPO that confirms the original observations of less anemia and fewer transfusions in those patients randomized to receive EPO concurrently with paclitaxel and carboplatin. METHODS: Thirty patients with advanced head and neck or lung carcinoma were treated with 2 courses of paclitaxel, 230 mg/m(2), and carboplatin, 7.5 mg/mL/minute, repeated every 21 days. The treatment group was comprised of 15 patients randomized to receive concurrent EPO, 150 U/kg, 3 times per week; in patients deemed nonresponsive the dose was increased to 300 U/kg and 450 U/kg in subsequent courses. The control group was comprised of 15 patients randomized not to receive EPO. RESULTS: Twenty-seven patients were evaluable. After 2 courses of chemotherapy the mean hemoglobin decrease was 1.2 g/dL in the EPO group versus 2.8 g/dL in the control group (P = 0.037). There was a highly significant decrease in hemoglobin over time in patients who did not receive EPO (P = 0.008). After 4 courses of chemotherapy, fewer patients were transfused in the EPO arm: 2 of 13 (15%) in the EPO treatment group versus 5 of 14 (36%) in the control group. CONCLUSIONS: There was significantly less anemia and transfusions were reduced by 50% in patients randomized to receive EPO during chemotherapy with paclitaxel and carboplatin.

Primary and recurrent early stage laryngeal cancer: preliminary results of 2-[fluorine 18]fluoro-2-deoxy-D-glucose PET imaging.

PURPOSE: To evaluate the effectiveness of 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in the identification of early stage (T1-T2) primary and recurrent laryngeal cancer. MATERIALS AND METHODS: Twelve patients with T1 or T2 laryngeal cancer underwent imaging prospectively with PET. Seven patients had new disease, and five had recurrent disease. All patients underwent imaging prior to planned therapy and tissue biopsy. PET images were evaluated by using standardized uptake ratios and visual analysis. RESULTS: Histopathologic evidence of early stage cancer was documented in the 12 patients. One had a carcinoma in situ, nine had T1 tumors, and two had T2 tumors. Of the 12 patients, 10 had vocal cord tumors, one had a hypopharyngeal tumor, and one had a preepiglottic tumor. Eleven (92%) patients with early stage cancer had standardized uptake ratios indicative of malignancy (mean, 4.6; SD, 1.8; 95% CI, 1.2; range, 2.8-7.6). One had false-negative results (standardized uptake ratio = 2.3). Nine underwent CT, and results in the larynx were normal in seven and abnormal in two. CONCLUSION: FDG PET can be used to identify primary and recurrent early stage laryngeal cancer. It may be useful for follow-up after therapy.

Correlation of CT-guided fine-needle aspiration biopsy of the liver with fluoride-18 fluorodeoxyglucose positron emission tomography in the assessment of metastatic hepatic abnormalities.

Imaging studies using the fluoride-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan have recently become available for patient neoplasia evaluation. Fine-needle aspiration (FNA) biopsy is a well-described diagnostic method for hepatic lesion evaluation. Correlation of these testing modalities in hepatic abnormalities has not been previously reported. Pathology files of Saint Louis University Hospital were retrospectively searched for patients with FNA biopsy of the liver. Thirty-one patients with a total of 32 FNA biopsies of the liver with corresponding FDG-PET scans were identified. Twenty-five patients had 25 cases of metastatic malignant neoplasia diagnosed by FNA biopsy. Of these cases, all but one had an FDG-PET scan positive for malignancy, yielding a sensitivity of 96% (24/25) for the FDG-PET scan. Combined positivity of the two testing modalities yielded a sensitivity of 100% (24/24). Seven patients did not demonstrate neoplasia by FNA biopsy, and the FDG-PET scan was negative in 6 of these 7 cases. The FDG-PET scan is an important imaging technique and, combined with FNA biopsy, can provide reliable diagnostic results and assist in the guidance of oncologic patient management.

Flow cytometric immunophenotyping of bone marrow core biopsies: report of 8 patients with previously undiagnosed hematologic malignancy and failed bone marrow aspiration.

OBJECTIVE: To report a method for flow cytometric immunophenotyping (FCI) bone marrow (BM) core biopsies in patients with hematologic malignancies of the BM who present with a failed BM aspiration ("dry tap"). DESIGN AND SETTING: Core biopsy specimens of BM were obtained from 8 patients who presented with previously undiagnosed hematologic malignancies arising in (7 cases) or secondarily involving (1 case) the BM and a dry tap. Suspensions of the BM core biopsy specimens were prepared and analyzed by FCI methods. DATA EXTRACTION AND DATA SYNTHESIS: The FCI data were analyzed in conjunction with cytomorphologic, histologic, immunohistochemical, and cytogenetic findings in all cases to determine a final diagnosis. CONCLUSIONS: The prepared BM core suspensions were viable and allowed for a complete immunophenotype profile by FCI in all cases, resulting in a clear definition of the cell of origin of the hematologic malignancy. Because of lack of preservation of architectural features and the potential for artifactual alterations of the relative frequency of abnormal cells, the FCI data must always be correlated with histologic sections of the BM biopsy.

Correlation of fine needle aspiration biopsy and fluoride-18 fluorodeoxyglucose positron emission tomography in the assessment of locally recurrent and metastatic head and neck neoplasia.

OBJECTIVE: Patients with primary head and neck neoplasia can present during follow-up with suspected recurrence, and both fine needle aspiration biopsy (FNAB) and fluoride-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan are available methodologies for evaluating these patients. Our objective was to retrospectively correlate patients who underwent both FNAB and FDG-PET scan in order to assess the possibility of recurrent neoplasia. STUDY DESIGN: The cytopathology files at Saint Louis University Health Sciences Center were retrospectively searched for patients with known primary head and neck malignancies beginning in 1995. Suspected recurrence and local metastases evaluated by both FNAB and FDG-PET scan were correlated. RESULTS: Twenty-eight patients received a combined total of 37 FNABs with concurrent FDG-PET scans. The majority of patients had primary oropharyngeal squamous cell carcinoma with intermixed, single cases of other primary head and neck neoplasms. Thirty of the 32 aspirates with recurrent or locally metastatic disease had combined positive findings by both FNAB and FDG-PET scan, yielding a sensitivity of 94%. One nonspecific and one negative FDG-PET scan came from a patient who had disease confirmed by FNAB. Five patients had negative findings by both methods that were supported by the subsequent clinical course. CONCLUSION: FNAB can provide confirmatory evidence of disease in a clinically suspicious abnormality with nonspecific FDG-PET results. FNAB and FDG-PET are highly sensitive for tumors in cases of clinically suspected recurrence and locally metastatic disease.

Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography.

BACKGROUND: [F-18]Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can measure the metabolic activity of tissues; FDG-PET may be able to predict response to chemotherapy by identifying changes in tumor metabolism. Measurement of response to treatment may help improve survival in the management of advanced head and neck cancer. We evaluated this particular use of FDG-PET in patients participating in a neoadjuvant organ-preservation protocol using taxol and carboplatin and compared pathologic response after chemotherapy with changes in tumor metabolism measured by FDG-PET. METHODS: Serial FDG-PET studies (n = 56) were performed in patients (n = 28) with stage III/IV head and neck cancer participating in a neoadjuvant organ-preservation protocol. The FDG-PET studies were performed before and after chemotherapy. All patients had tissue biopsies before and after chemotherapy. Patients were classified as pathologic complete response (PCR) or residual disease (RD) based on tissue biopsies. Visual analysis of PET scans was performed to identify patients with complete response by PET, and these findings were compared with pathology results. Metabolic changes were also evaluated using standardized uptake ratios (SUR) of FDG. RESULTS: The sensitivity and specificity of PET for residual cancer after therapy was 90% (19/21) and 83% (5/6), respectively. Two patients had initially negative biopsies and positive PET studies for persistent disease. Pathology review and rebiospy led to confirmation of the PET results in these cases, giving a sensitivity of 90% for initial tissue biopsy. CONCLUSIONS: In this preliminary analysis, FDG-PET was accurate in classifying response to chemotherapy in most patients. Fluorodeoxyglucose-PET may identify residual viable tumor when it is otherwise undetectable.

Expression of p53 protein in advanced head and neck squamous cell carcinoma before and after chemotherapy.

BACKGROUND: The expression of p53 protein has been reported to be in the range of 35% to 67% in head and neck squamous cell carcinoma (HNSCC). Mutations of the gene for p53 protein have been associated with rapidly proliferating tumors, and p53 protein expression has been shown to be a significant predictor of worse survival in surgically resected HNSCC. To determine whether p53 protein expression in advanced (stages III and IV) HNSCC has any impact on tumor response to 2 to 3 courses of paclitaxel (Taxol) and carboplatin, we prospectively studied prechemotherapy specimens from patients with previously untreated, advanced-stage HNSCC. We also attempted to study residual tumors after chemotherapy to determine if the p53 status of the tumor changed. DESIGN: The expression of p53 protein was evaluated by immunohistochemical analysis (clone BP53-12-1; Bio-Genex, San Ramon, Calif). SETTING: Tertiary university medical center. INTERVENTION: Two to 3 courses of chemotherapy with paclitaxel and carboplatin. MAIN OUTCOME MEASURES: Pathologic complete remission or residual tumor. RESULTS: The results of p53 immunostaining were positive in 24 (67%) of 36 HNSCC specimens before chemotherapy. After chemotherapy, 8 patients achieved pathologic complete remission. Before chemotherapy, the tumor was p53 negative in 2 patients and positive in 6 patients. CONCLUSIONS: No correlation of p53 protein expression with response to chemotherapy was noted. The expression of p53 protein converted from positive to negative in 5 (42%) of 12 specimens from patients with residual tumor after chemotherapy, with no impact on clinical outcome.

A phase I report of paclitaxel dose escalation combined with a fixed dose of carboplatin in the treatment of head and neck carcinoma.

BACKGROUND: Standard therapy for advanced head and neck carcinoma is surgery and radiation, and the subsequent 5-year survival with this treatment has been less than 50%. New combined modality treatment strategies are being tested to improve survival. New chemotherapy combinations are being developed and administered simultaneously with, or sequenced with, radiation and surgery. This article reports the Phase I results of administering paclitaxel and carboplatin preoperatively. The authors' objective was to develop an outpatient chemotherapy that would downstage tumors and allow organ preservation with equal or improved survival as compared with standard therapy. METHODS: Thirty-six patients with untreated Stage III/IV head and neck carcinoma were treated and were evaluable for toxicity. All patients had lesions that were measurable in perpendicular planes. A nonrandomized, Phase I design was used, according to which cohorts of patients were treated every 21 days with escalating doses of paclitaxel (150-265 mg/m2) given as a 3-hour infusion immediately preceding carboplatin. Premedication was used to avoid acute hypersensitivity reactions. Carboplatin was administered intravenously over 1 hour at a constant dose calculated with the Calvert formula (area under the curve, 7.5). RESULTS: The dose-limiting toxicities were neuropathy and thrombocytopenia at a paclitaxel dose of 265 mg/m2. Neutropenic fever was observed in 30% of patients at a paclitaxel dose of 250-265 mg/m2. Other observed adverse effects included pruritus, myalgia, arthralgia, alopecia, nausea, and vomiting. CONCLUSIONS: Toxicity was acceptable. The maximum tolerated dose of paclitaxel was 230 mg/m2 without hematopoietic growth factor, or 250 mg/m2 with hematopoietic growth factor, the carboplatin dose held constant, calculated at area under the curve of 7.5. Phase II studies of this combination are warranted in the treatment of these carcinomas.

Erythropoietin reduces anemia and transfusions after chemotherapy with paclitaxel and carboplatin.

BACKGROUND: The authors report on anemia observed during preoperative paclitaxel and carboplatin chemotherapy in patients with advanced head and neck carcinoma and discuss how the use of recombinant human erythropoietin (r-HuEPO) ameliorates this anemia, reducing the need for subsequent packed red blood cell (PRBC) transfusions. METHODS: Response to r-HuEPO was defined as reduced hemoglobin fall during preoperative chemotherapy and reduced transfusion requirements during surgery. Thirty-six patients with advanced head and neck carcinoma were evaluable after treatment with preoperative chemotherapy using paclitaxel and carboplatin. Group 1 was comprised of 14 patients who empirically received r-HuEPO at a dose of 150 U/kg 3 times per week for 3 weeks; in patients deemed nonresponders, the dose was increased to 300 U/kg and 450 U/kg in the subsequent courses. Group 2 was comprised of 22 patients who did not receive r-HuEPO. RESULTS: During preoperative chemotherapy, the mean hemoglobin fall was 0.5 g/dL in Group 1 (P = 0.40). In Group 2 there was a statistically significant mean hemoglobin fall of 3.3 g/dL (P < 0.0001). There was also a nonstatistically significant trend toward fewer PRBC transfusions: none of 14 patients (0%) in Group 1 versus 4 of 22 patients (18%) in Group 2 (P = 0.141). CONCLUSIONS: A significant fall in hemoglobin and an increase in the need for transfusions were observed in head and neck carcinoma patients receiving carboplatin and paclitaxel chemotherapy prior to surgery. Empiric r-HuEPO therapy appeared to prevent anemia and reduced the need for PRBC transfusions.

Changes in quality-of-life scores in a population of patients treated for squamous cell carcinoma of the head and neck.

BACKGROUND: Quality of life levels fluctuate depending on treatment type and at various points throughout treatment. In patients with advanced head and neck cancer, quality of life is thought to be treatment dependent. The purpose of this study is to compare levels of patients self-reported quality of life across treatment. PATIENTS AND METHODS: Preliminary data presented here are based on 24 patients enrolled so far in an experimental organ-preservation protocol. The two treatment groups consist of one group treated with chemotherapy (paclitaxel and carboplatin) followed by radiation therapy and the second group which is treated with chemotherapy (paclitaxel and carboplatin) followed by surgery and postoperative radiation. Data is collected pretreatment and at uniform points throughout the course of treatment. RESULTS: Preliminary results suggest that quality of life is significantly higher in the nonsurgical group than in the surgical group at the last treatment point reported. Social distress/avoidance is also lower in the nonsurgical group. Because of the small number of patients represented in this study, results should be interpreted with caution and should be viewed as descriptive at this juncture. CONCLUSION: Quality of life seems to be preserved in patients who experience less invasive and disfiguring treatment, and who also have compromised eating and communication abilities. Data collection in this study is ongoing.

Antifungal effects of yeast-derived rhu-GM-CSF in patients receiving high-dose chemotherapy given with or without autologous stem cell transplantation: a retrospective analysis.

Systemic fungal infections (SFI) in patients receiving high-dose chemotherapy (HDC) are a frequent cause of morbidity and mortality. Preclinical studies have reported augmented antifungal activity of monocytes, macrophage cells, and neutrophils exposed to certain colony-stimulating factors (CSF), including GM-CSF. We conducted a retrospective descriptive epidemiologic study to examine the characteristics of 145 consecutive patients receiving HDC administered with or without autologous stem cell transplantation (ASCT) and who subsequently received either GM-CSF and G-CSF, G-CSF alone, GM-CSF +/- IL-3 or no CSF. The analysis of this patient population sought to define the incidence of SFI and its relationship to therapy with monocyte/macrophage-stimulating (MMS group) cytokines (GM-CSF and G-CSF; GM-CSF +/- IL-3) or to cytokines which do not result in monocyte/macrophage stimulation (NMMS group, G-CSF alone or no CSF). Risk factors for the development of SFI were balanced between the MMS (n = 70) and NMMS (n = 75) groups. Two patients (2.9%) in the MMS and nine patients (12%) in the NMMS groups developed SFI. The risk ratio for developing SFI in the NMMS group compared to the MMS group was 4.20 (P = 0.023). This relationship was confounded, however, by the diagnosis of hematologic tumor or solid tumor (RR = 3.15, P = 0.082). SFI was the primary cause or major contributing factor in five of the 10 total deaths in our study population. Four SFI-related deaths occurred in the NMMS group and one SFI-related death occurred in the MMS group. Our data suggest a protective role for GM-CSF, IL-3 or other MMS cytokines in preventing SFI in patients receiving HDC. This should be further investigated as a potential complementary approach to conventional strategies in antifungal prophylaxis for patients receiving HDC.

Bilateral mucosa-associated lymphoid tissue lymphomas of parotid glands: a 13-year interval.

Benign lymphoepithelial lesions of salivary gland may have a population of monoclonal B cells. There is controversy regarding the clinical significance of monoclonality in these lesions. Morphologically and clinically, benign lymphoepithelial lesions of the salivary gland with monoclonal B cells falls within the spectrum of low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. We report a case of bilateral parotid lymphomas of mucosa-associated lymphoid tissue, separated diagnostically by a 13-year interval. Polymerase chain reaction analysis detected similar clones in the bilateral parotid glands. This finding supports the natural history of mucosa-associated lymphoid tissue lymphomas. In addition, because mucosa-associated lymphoid tissue lymphomas have an unpredictable period of localized disease, recognition of monoclonality in benign lymphoepithelial lesions of salivary glands is important for local cure and can be aided by combining histologic with immunohistochemical, flow cytometric immunophenotyping, and Southern blot and/or polymerase chain reaction analysis.

B-cell lymphoproliferative disorder complicated by a natural killer cell lymphoproliferative disorder of granular lymphocytes associated with T-cell gene rearrangement: case report and review of the literature.

We report an unusual case of natural killer cell lymphoproliferative disorder of granular lymphocytes associated with a T-cell receptor (TCR)-beta gene rearrangement. The patient developed the disorder 1 month after cessation of fludarabine therapy for a B-cell lymphoproliferative disorder. The B-cell lymphoproliferative disorder was no longer detectable when the natural killer cell lymphoproliferative disorder persisted. Review of the literature reveals only one reported case of natural killer cell lymphoproliferative disorder of granular lymphocytes associated with a TCR-delta gene rearrangement.

Gastrointestinal disease in patients receiving salvage chemotherapy or bone marrow transplantation.

Thirty-three patients receiving either salvage chemotherapy or bone marrow transplantation with potential surgical illness related to gastrointestinal symptoms were identified. Sixty-nine percent of patients received salvage chemotherapy for either hematological (61%) or visceral malignancies (39%). Twenty-one percent of patients had a previous bone marrow transplant. Twenty-two (66%) had an absolute neutrophil count less than 10(3)/mm3. Ulcerative foregut disease (51%) and perianal disease (21%) were the most common disease entities identified. Esophagogastroduodenoscopy (79%) and anorectal examination under anesthesia (21%) provided the greatest diagnostic yield. The mean hospitalization was 21 days. Surgery was performed in 21% of patients, but was seldom required for abdominal pain or intestinal bleeding. Perianal disease was often chronic and required multiple operative procedures. Overall, a 27% mortality was found. Gastrointestinal disease in patients receiving salvage chemotherapy or bone marrow transplantation is usually manifested by bleeding and localized to the proximal gut, or related to perianal disease.