Clinical Stage IVB Research Articles

Long-term results of definitive chemoradiotherapy for unresectable locally advanced esophageal squamous cell carcinoma.

PurposeThe present study aimed to evaluate the long-term results of definitive chemoradiotherapy (CRT) for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC).Materials and methodsWe analyzed eighty patients with unresectable LA-ESCC, who underwent definitive CRT between 2001 and 2014. The 5-year overall survival (OS), cause-specific survival (CSS), and progression-free survival (PFS) rates were calculated, and we investigated the prognostic factors and adverse events.ResultsThe median age was 66 years (range, 41–83 years). Histologically, all patients had squamous cell carcinoma. The most common tumor site was the middle thoracic esophagus in 43 (54%) patients. According to the eighth edition of the Union for International Cancer Control TNM classification, sixty-six patients (83%) had T4 disease, 59 (74%) had regional lymph node (LN) metastases, and 35 (44%) had distant LN metastases beyond the regional LN (M1 LYM) disease. Forty-five (56%) and 35 (44%) patients belong to clinical stages IVA and IVB, respectively. The median follow-up period for survivors was 86 months. The 5-year OS, CSS, and PFS rates were 20.2%, 25.7%, and 18.4%, respectively. On univariate analysis, only the performance status score was significantly associated with better overall survival (p = 0.026). Grade 3 or higher late adverse events were observed in 12 (15%) patients, and these included cardiopulmonary adverse events in 6 (8%) patients. Treatment-related death occurred in 3 (4%) patients.ConclusionWe showed the long-term results of definitive CRT for unresectable LA-ESCC. The survivals are still poor and new treatment strategies need to be developed.

Impact of the Cholangiocarcinoma Component of Combined Hepatocellular/Hepatocholangiocarcinoma on Patient Survival

Abstract Introduction/Objective The radiopathologic correlation, overall prognosis, and best management of combined hepatocellular carcinoma/cholangiocarcinoma (HCC/CC) remains uncharted territory. Methods We studied whether the percentage (%) of the cholangiocarcinoma (CC) component of HCC/CC impacted patient survival. A retrospective analysis was performed including all cases (18) of HCC/CC in the pathology archives from 2011–2019. Tumor beds were submitted entirely in all but 2 specimens, which were representatively sampled. Slides from these cases were reviewed to assess % of CC. Survival was calculated from the date of diagnosis to the date of demise and censored as the date last known alive at the time of the study. Results 13 cases were liver explants, 2 were resections, and 3 were biopsies. 13 cases were from clinical stage II patients, 2 were clinical stage IVA, and 2 were clinical stage IVB. All but one patient in the study group were males. There was no predilection for any specific tumor site. The cases were divided into three groups related to CC percentage: 0–20 (n=5), 21–40 (n=6), and >40% (n=7). AFP was variably elevated in select cases, with the highest values found in the medium and high % groups. Though there was no significant difference in overall survival among the three groups, mean and median survival trended in a downward fashion with increased % CC. Interestingly, radiology read 12 cases as HCC, 1 as intrahepatic CC, and only 1 as cholangiocarcinoma/hepatoma, atypical for HCC. Conclusion We conclude that there is a trend for decreased survival as % CC increases in combined HCC/CC patients, with patients with >20% CC tending to have lower survival rates. Furthermore, incongruity exists between radiologic and pathologic diagnoses of combined HCC/CC. Additional study with a larger sample size will yield more information to understand better prognosis as well as guide more accurate diagnosis of these patients.

A phase II study of rh-endostatin combined with paclitaxel and nedaplatin in treating patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

4522 Background: For patients (pts) with metastatic ESCC, the prognosis is poor. Rh-endostatin (endostar), a potent inhibitor of angiogenesis, has shown clinical activity when combined with chemoradiotherapy in treating locally advanced ESCC. This single-arm phase 2 study was designed to assess the efficacy and safety of endostar combined with paclitaxel and nedaplatin in treating pts with recurrent or metastatic ESCC. Methods: Eligible pts had recurrent or metastatic ESCC and Karnofsky score ≥70. Endostar (30 mg/day, continuous infusion, day 1-14) plus paclitaxel (150 mg/m2, day 4) and nedaplatin (80 mg/m2, day 4) were administered every 3 weeks for 6 cycles followed by maintenance therapy with endostar. Primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AEs). Results: From January 2015 to August 2019, 53 pts were enrolled. 44 (83%) pts were male. The median age was 59 years. 43 (81%) pts had pathology of poor or moderate differentiated ESCC. The middle and lower thirds of the esophagus (81%) were the most common primary tumor sites. 11 (21%) patients had undergone esophagectomy. At the time of treatment, 49 (93%) pts were diagnosed with clinical stage IVB. The most common metastatic sites were lymph node (91%), lung (32%) and liver (26%). 50 pts were assessable for response. No complete response was observed. 21 pts achieved a best response of partial response and 14 pts had stable disease. ORR was 42% and DCR was 70%. The median PFS and OS was 5.1 months (95% CI 3.7-6.6 months) and 13.2 months (95% CI 8.0-18.4 months) respectively. The most common AEs observed during this study were anemia (49.1%), neutropenia (34%), fatigue (28.3%) and anorexia (26.4%). The most common Grade 3/4 AE observed was neutropenia (17%). Conclusions: The combination of endostar plus paclitaxel and nedaplatin is a well tolerated treatment modality with promising activity in previously untreated recurrent or metastatic ESCC. Its efficacy and safety could be further studied in randomized trials. Clinical trial information: NCT02350517 .

525P - Retrospective analysis of outcomes of cisplatin and irinotecan combination chemotherapy for unresectable thymic carcinoma

BackgroundThymic carcinoma is a rare, malignant mediastinal tumor originating from thymic epithelial cells. It exhibits a tendency for metastasis and invasive growth. Unresectable thymic carcinoma is treated with systemic chemotherapy. However, a definitive chemotherapeutic regimen for this entity is yet to be established. The objective of this study was to evaluate the efficacy and safety of cisplatin and irinotecan combination as the first-line chemotherapy. MethodsData pertaining to patients with advanced thymic carcinoma who received cisplatin and irinotecan combination chemotherapy between January 1, 2002 and December 31, 2018, were retrospectively analyzed. The end points were disease control rate, progression free survival, and overall survival. The incidence of significant hematological and non-hematological toxicity was also assessed. ResultsWe identified 17 patients with a median age of 56 years (ECOG performance status: 0 or 1). All patients had clinical stage (Masaoka-Koga staging system) IVa or IVb. Disease control was achieved in 15 patients (88.2%). Median progression-free survival was 7.3 months [95% confidence interval (CI) 2.7–11.6]; median overall survival was 45.6 months (95% CI 9.49–69.5). The outcomes were similar to those achieved with previously reported chemotherapy regimen, CBDCA plus paclitaxel or Cisplatin combination chemotherapy. No treatment-related deaths occurred in this cohort. Grade 3 or worse hematological toxicity was observed in five patients (neutropenia: three patients; anemia: two patients); grade 3 or worse non-hematological toxicity was observed in three patients. None of the patients developed febrile neutropenia. ConclusionsCisplatin and Irinotecan combination chemotherapy may be a safe and effective first-line chemotherapy regimen for unresectable thymic carcinoma. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureY. Hosomi: Honoraria (self): AstraZeneca. All other authors have declared no conflicts of interest.

Supraclavicular lymphadenopathy as the initial manifestation in carcinoma of cervix

Carcinoma of the cervix has been considered as a preventable disease. However, it continues to be a significant health problem worldwide and is the second most frequent cause of cancer death among women in developing countries. It rarely metastasizes to the supraclavicular group of lymph nodes during the initial presentation, and few cases have been reported in the literature. Here, we report a case of cervical carcinoma in a 40-year-female with unusual manifestation at the time of initial presentation. The patient was diagnosed with squamous cell carcinoma of the cervix with supraclavicular lymph node metastatic FIGO Clinical Stage IVB and treated in the line of concurrent chemoradiotherapy followed by adjuvant chemotherapy. The patient is reported to be disease-free after 1 year of completion of therapy.

Prognostic significance of inflammatory parameters and nutritional index in clinical stage IVB endometrial carcinomas

Recently, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) or prognostic nutritional index (PNI) have been investigated as prognostic parameters in various malignancies. Herein, we detail how we have investigated the prognostic significance of NLR, PLR and PNI together with the other clinicopathological factors for International Federation of Gynaecology and Obstetrics stage IVB endometrial carcinoma. Thirty-two patients with clinical stage IVB disease were enrolled. The relationship between clinicopathological factors, NLR, PLR or PNI and overall survival (OS) rates was investigated. The 5-year OS rate was 9.7%, and the median survival time was 9 months. In univariate analysis, PS 0–1, G1–2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. In multivariate analysis, only a histology (G1–2 endometrioid carcinoma) was identified as an independent favourable prognostic factor. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma.Impact StatementWhat is already known on this subject? Several parameters representing the systemic inflammatory response (e.g. neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR)) or the nutritional condition (e.g. prognostic nutritional index (PNI)) have been investigated as prognostic parameters in various malignancies, whereas they have not been thoroughly investigated in endometrial carcinoma.What the results of this study add? In univariate analysis of various factors for overall survival, the performance status (PS) 0–1, grade 1–2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. However, in a multivariate analysis, only the histology (grade 1–2 endometrioid carcinoma) was identified as an independent favourable prognostic factor.What the implications are of these findings for clinical practice and/or further research? This retrospective study identified that neither inflammatory parameters nor the nutritional index were revealed to be independent prognostic factors by multivariate analyses. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma to improve the poor prognosis of this disease.

Anaplastic thyroid cancer: multimodal treatment results.

BackgroundAnaplastic thyroid cancer is a rare and lethal disease. It accounts for 1–2% of thyroid malignancies, but specific mortality is higher than 90%. It is an aggressive locoregional disease with a high metastatic capacity. There is no agreement with regards to the best treatment. We analysed the results of treatment in a mestizo population treated in the National Cancer Institute (Mexico).MethodsWe reviewed 1,581 files of thyroid carcinomas; of these, 29 (1.83%) had anaplastic thyroid carcinoma. Demographic variables, clinical manifestations, tumour characteristics, and treatments were analysed.ResultsThe median age was 64.5 ± 13.2 years. Females were more affected (female/male ratio: 2.6:1); 21 cases occurred in women (72.4%), and eight in males (27.6%). The most common manifestations were neck enlargement (93.10%) and hoarseness (71.31%). The median tumour size was 8 cm (range: 4–20 cm). The percentage of cases which presented in clinical stage IVA was 10.3%, with 62.1% presenting in clinical stage IVb and 27.6% presenting in clinical stage VIc. Complete resection (R0) (p = 0.05), radiation doses of higher than 33.1 Gy (p = 0.04), and multimodal therapy were associated with better survival. Surgery plus radiotherapy with or without systemic treatment (p = 0.006). The median overall survival was 119 days (IC 95%, 36.3–201.6). Six-month, one-year and two-year survival was 37.9%, 21% and 13%, respectively.ConclusionComplete surgical resection is associated with better survival but is very difficult to achieve due to aggressive biological behaviour. Multimodal therapy is associated with better survival and a better quality of life. There is a need for more effective systemic treatments as extensive surgical resections have little overall benefit in highly invasive and metastatic disease.

Status of treatment for the overall population of patients with stage IVb endometrial cancer, and evaluation of the role of preoperative chemotherapy: A retrospective multi-institutional study of 426 patients in Japan

ObjectiveWe previously reported on the role of cytoreduction in 248 patients with surgical stage IVb endometrial cancer (EMCA). This study aimed to evaluate the clinical characteristics, prognosis according to initial treatment, and impact of preoperative chemotherapy in the overall population of patients with clinical and surgical stage IVb EMCA. MethodsA multi-institutional retrospective analysis was performed in 426 patients diagnosed with clinical and surgical stage IVb EMCA from 1996 to 2005. Factors associated with overall survival (OS) were identified using univariate and multivariate analyses. ResultsThe median OS for all 426 patients was 14months. Patients were divided into three groups according to their initial treatment: primary surgery group (n=279), primary chemotherapy group (n=125), and palliative care group (n=22). The median OS times for these groups were 21, 12, and 1month, respectively (p<0.0001). Patients in the primary surgery group had better performance status (PS) and lower numbers of extra-abdominal metastases than those in the primary chemotherapy group. Multivariate analysis identified good PS, endometrioid histology, absence of clinical intra-abdominal stage IVb metastasis, hysterectomy, and chemotherapy as independent predictors of OS. In the primary chemotherapy group, 59 patients subsequently underwent surgery, and these patients had similar OS to those in the primary surgery group. ConclusionsHysterectomy and chemotherapy may prolong OS in selected patients with stage IVb EMCA. Our data suggest that primary chemotherapy followed by surgery may be a useful treatment choice in patients not suitable for primary surgery.

Stanford V chemotherapy and involved field radiotherapy for children and adolescents with unfavorable risk Hodgkin lymphoma: Results of a multi-institutional prospective clinical trial.

9502 Background: To evaluate the efficacy of 12 weeks of Stanford V chemotherapy (prednisone, vinblastine, doxorubicine, nitrogen mustard, etoposide, vincristine, and bleomycin) without routine growth factor support plus response-adapted low-dose, involved-field radiotherapy (IFRT) in children and adolescents with unfavorable risk Hodgkin lymphoma (HL). Methods: Multi-institutional (St. Jude Children’s Research Hospital, Stanford University, Children’s Hospital Boston, Massachusetts General Hospital and Maine Children’s Hospital) clinical trial. One hundred forty-one patients with clinical stages IIB (n=43), IIIB (n=19), IVA (n=27), and IVB (n=52) HL were treated with 12 weeks of Stanford V chemotherapy and low dose IFRT between June 2002 and May 2011. Involved nodal sites in complete remission (CR, defined as &gt; 75% shrinkage of the original tumor and PET negative) after 8 weeks of Stanford V received 15 Gy IFRT; those sites that achieved only partial response received 25.5 Gy IFRT after completion of all 12 weeks of chemotherapy. Results: With a median follow-up of 4.6 years, the 3-year overall and event-free survival (EFS) are 97% (SE=2%) and 79% (SE=4%) respectively. There was no significant difference in EFS by stage (IIB vs. IIIB vs. IV; P=0.84). Ten patients developed progessive disease and 18 relapsed, while 5 have died (1 after relapse in an accident and 4 of refractory disease). Most common toxicities were grade 3 hematologic with 234 episodes of neutropenia in 101 patients (72%) and 85 episodes of anemia in 52 patients (37%); Fever and neutropenia occurred 13 times in 12 patients (9%). Conclusions: Risk-adapted, combined-modality therapy using 12 weeks of Stanford V chemotherapy plus IFRT is well tolerated in this population with manageable acute toxicities. Overall survival is comparable to other more intense chemotherapy regimens. Future high-risk front line therapies may consider a Stanford V backbone with targeted intensification and further tailoring of radiation therapy.

Successful Treatment of Immunodeficiency-Associated EBV-Negative Lymphoproliferative Disorders in Rheumatoid Arthritis by Methotrexate Withdrawal and Prevention of its Relapse by Rituximab Administration

Immunodeficiency-associated lymphoproliferative disorders (LPD) in rheumatoid arthritis are a rare, aggressive, and life-threatening clinical entity. We describe a 60-year-old man who had rheumatoid arthritis that was treated with methotrexate. Eight months after the treatment, the case was diagnosed as Epstein-Barr virus-negative LPD (diffuse large B-cell lymphoma) with abdominal bulky mass and clinical stage IVB at high risk in the international prognostic index. Immediate withdrawal of methotrexate led the patient to achieve complete remission, and 8 subsequent courses of rituximab treatment for the prevention of relapse kept the patient disease-free for 29 months. Our case suggests that these treatments may be an effective, safe, and feasible strategy for immunodeficiency-associated LPD in rheumatoid arthritis.

Letters to Editor Isolated metastasis to the foot as an extremely rare presenting feature of primary endometrial cancer. and review of the literature

Letters to Editor Isolated metastasis to the foot as an extremely rare presenting feature of primary endometrial cancer. and review of the literature

Super-acute onset of tumor lysis syndrome accompanied by hypercytokinemia during treatment of Hodgkin's lymphoma with ABVD chemotherapy

Background: Tumor lysis syndrome (TLS) is a group of life-threatening metabolic complications that can occur after initiation of cancer chemotherapy. Onset of TLS in the middle of chemotherapy, however, has not been reported previously in patients with hematologic malignancies. Objective: We report a case of a patient who experienced TLS of super-acute onset accompanied by hypercytokinemia during chemotherapy treatment with a combination of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD). Case summary: A 36-year-old Japanese man (height, 182 cm; weight, 83 kg; body surface area, 2.04 m 2) was admitted to the hospital for the treatment of malignant lymphoma (clinical stage IVB Hodgkin's lymphoma). Chemotherapy was initiated using the ABVD regimen (doxorubicin [Adriamycin] 25 mg/m 2 by 30-minute infusion, bleomycin 9 mg/m 2 by 30-minute infusion, vinblastine 6 mg/m 2 by bolus injection, and dacarbazine 375 mg/m 2 by 2-hour infusion). During the dacarbazine infusion, the patient's body temperature rose from 36.5°C to 42°C; he experienced a convulsion and then lost consciousness. The convulsion was not suppressed despite the use of diazepam (5 mg IV twice) and phenytoin (500 mg IV). The patient was then transferred to the intensive care unit and sedated using a continuous infusion of midazolam (10 mg/h). Levels of serum lactate dehydrogenase, aspartate aminotransferase, uric acid, blood urea nitrogen, and creatinine evaluated shortly after the ABVD regimen were outside normal limits. In addition, interleukin-6 (IL-6) concentrations were elevated to 54,220 pg/mL. Continuous hemodiafiltration was immediately performed to lower the elevated levels of IL-6. The next day, IL-6 concentrations decreased to 97 pg/mL, and the patient was weaned from ventilator support and sedation. The patient had no adverse effects after the event. According to the results of an assessment using the Naranjo adverse drug reaction probability scale (score = 3), the development of TLS in this patient was possibly related to the chemotherapy regimen. Conclusions: ABVD chemotherapy was possibly associated with the super-acute onset of TLS in this patient. In addition, hypercytokinemia occurred with TLS, which led to pyrexia, convulsion, and loss of consciousness.

Preservation of the Internal Jugular Vein in the Radical Treatment of Node-Positive Neck—Is It Safe?

The aim of this study was to evaluate risk factors of neck recurrence in patients with pN+ necks submitted to a modified or a classic radical neck dissection and the safety of preserving the internal jugular vein in the treatment of a subgroup of these patients. The medical records of 311 untreated patients with squamous cell carcinoma of the oral cavity (106 cases), oropharynx (95 cases), larynx (49 cases), and hypopharynx (61 cases) were reviewed. Their clinical stages (CS) were CS II in 1%, CS III in 19.9%, CS IVA in 76.2%, and CS IVB in 19.6% of the cases. All patients were pN+. Ipsilateral neck recurrence occurred in 18 cases (5.8%), 14 cases (4.5%) where the internal jugular vein was resected, and 4 cases (1.3%) where the internal jugular vein was preserved. Neck recurrence did not have significant correlation with tumor site (P = .852), T stage (P = .369), N stage (P = .963), adjuvant radiotherapy (P = .701), number of positive lymph nodes (P = .886), jugular vein preservation (P = .240), and extracapsular spread (P = .670). There was significant correlation between neck recurrence and the lymph node size (.040). Modified radical neck dissection with internal jugular vein preservation can be performed in selected patients with lymph node metastases, with no significant increase in the risk of neck recurrence.

Epstein-Barr Virus: Main Pathogenic Agent in Hodgkin Lymphoma Associated Hemophagocytic Syndrome?.

Hemophagocytic syndrome (HPS) is characterized by an uncontrolled proliferation of macrophages displaying extensive phagocytosis of hematopoietic cells that can be associated with non Hodgkin lymphomas. However, Hodgkin lymphoma associated with hemophagocytic syndrome (HL-HPS) has rarely been published. We report here a large series of 34 patients presenting HL-HPS. Histological analysis and Epstein-Barr Virus (EBV) studies were performed. The 34 patients were enrolled from 1992 to 2006. HPS diagnosis was based on usual clinico-biological criteria. Bone marrow aspiration or biopsy were performed in all cases and confirmed HPS, showing hemophagocytic features in scattered macrophages. HL was documented on histological material in all 34 patients. The biopsies were performed on different localizations: lymph nodes (n=18), bone marrow (n=27), liver (n=2) and tonsil (n=1). All histological slides were reviewed and classified according to the World Health Organization (WHO) Lymphoma classification. The presence of EBV in the tumour cells was detected using EBER RNA in situ hybridization and the expression of viral proteins LMP-1, EBNA-2 by immunoperoxidase. Patients were 26 men and 8 women (sex ratio M/F = 3.3). The median age was 45 years (range 19–84). HIV status was negative in 26 patients and positive in 8 patients. All patients were in clinical stage IVB. HL subtypes (18 lymph nodes) were Mixed Cellularity (n=12, 67%), Nodular Sclerosis (n=2, 11%) and Lymphocyte Depleted (n=4, 22%). Extra nodal tissues were highly infiltrated by tumour cells in all cases. The presence of EBV in tumour cells was detected in 32 out of the 34 patients (94%). In all EBV positive cases, high levels of LMP-1 without EBNA2 expression were detected, defining a latency II. This study reports the largest series to date of HL-HPS. The features of HL-HPS are particular by the high proportion of mixed cellularity subtypes (67%) in contrast to the frequency of nodular sclerosis subtypes observed in the general population of non overt immunosuppressed patients, and by the striking high proportion of EBV associated HL (32 out of the 34 patients, 94%). Our findings suggest not only a pathogenic role of EBV, but also a defective immune system in the control of EBV infection in HL-HPS patients.The high predominance of male in our population of HPS-HL (sex ratio M/F = 4.3 after exclusion of HIV positive patients) and the strong association with EBV could suggest X-linked immune defect in these patients.

Hodgkin’s lymphoma relapse in the uterine cervix 15 years after the initial cure

Uterine cervix is an uncommon site for the presentation of Hodgkin's lymphoma. We describe a 62-year-old woman who developed an unusual relapse of classical Hodgkin's lymphoma, a nodular sclerosis subtype, in the uterine cervix, with propagation to the vaginal wall. She relapsed 15 years after achieving a complete remission of Hodgkin's lymphoma, initially in clinical stage IVB. This late relapse of the Hodgkin's lymphoma was in the clinical stage IEB and the treatment was initiated according to ABVD regimen. After the second course, lethal outcome ensued due to progression of the renal failure, which ensued in the meantime, probably as an adverse effect of the previous therapy.

P53 Mutations in Nasal Natural Killer/T-Cell Lymphoma from Mexico: Association with Large Cell Morphology and Advanced Disease

Nasal NK/T-cell lymphoma is a unique form of lymphoma highly associated with Epstein-Barr virus, and with a characteristic geographic distribution. Recently, we showed that p53 is overexpressed in a high percentage of nasal NK/T-cell lymphomas. The aim of this study was to analyze the status of the p53 gene, and correlate it with the expression of p53 protein and its downstream target, the cyclin-dependent kinase inhibitor p21, in a series of 25 cases of well-characterized nasal NK/T-cell lymphoma from Mexico. The highly conserved exons 5 to 8 of the p53 gene were amplified by polymerase chain reaction and screened for mutations by denaturing high-pressure liquid chromatography. Abnormal polymerase chain reaction products detected by denaturing high-pressure liquid chromatography and additional selected cases were sequenced. In addition, the incidence of loss of heterozygosity at the p53 locus was analyzed in 12 cases. Of the 25 patients, 17 were male and 8 female (M:F ratio, 2.1:1), with a median age of 43 years (range, 21 to 93 years). Morphologically, most of the cases were composed of a mixture of medium-sized cells and large transformed cells (21 cases), and four cases were composed exclusively of large transformed cells. Three different groups determined by p53 gene status and expression of p53 protein were identified: group 1 was p53 +/p53 mutated (five cases, all with p53 missense mutations). Morphologically, three of the five cases were composed of large cells. All five cases revealed overexpression of p53 in the majority of the tumor cells with a mean of 86%. Unexpectedly, three of these cases also showed overexpression of p21. Four of the five patients presented with clinical stage IVB and died with disease. Group 2 was p53+/p53 wild-type (10 cases). Histologically, nine cases were of the mixed type, and one of the large cell type. The percentage of p53 overexpressing cells was lower than in the previous group with a mean of 23%. p21 was positive in 7 of the 10 cases. Six patients in this group presented with clinical stages I to II and four patients with advanced disease (stage III and IV). Five patients are alive 12 to 120 months later (mean, 24 months), three with no evidence of disease. Group 3 was p53-/p53 wild-type (10 cases). All cases showed mixed cell morphology. p21 was positive in 5 of 10 cases. Four patients presented with clinical stage I to II and six patients with advanced disease. Four patients are alive with no evidence of disease 9 to 60 months later (mean, 10 months). Overall, p53 mutations were present in 24% (5 of 21) of the evaluable cases, all of them overexpressing p53 in the majority of tumor cells. Cases with p53 mutations were associated with large cell morphology (P = 0.0162) and presented more often with advanced stage disease. Loss of heterozygosity at chromosome 17p was found only in 2 of the 12 (17%) cases investigated, both cases showed p53 mutations of the remaining allele. P21 overexpression (60% of cases) is frequent in nasal NK/T-cell lymphoma and seems to be independent of p53 gene status. The overexpression of p53 and p21, independent of p53 mutations, although as yet not clear, might be the result of Epstein-Barr virus infection, and warrants further investigation.

Cytomegalovirus enteritis after autologous peripheral blood stem cell transplantation

A 61-year-old male with non-Hodgkin's lymphoma (peripheral T-cell lymphoma, unspecified, clinical stage IVb) received autologous peripheral blood stem cell transplantation (PBSCT) during first remission. He was seropositive for cytomegalovirus (CMV) prior to autologous PBSCT. His posttransplant clinical course was complicated by refractory CMV enteritis, which manifested persistent abdominal pain, diarrhea, and bloody stool. Generally, gastrointestinal CMV disease is relatively rare after autologous PBSCT. However, our case indicates that CMV infection must be considered as a differential diagnosis in cases of unexplained hemorrhagic enteritis following autologous PBSCT.

Advanced Hodgkin disease (clinical stages IIIB and IV): low relapse rate after brief chemotherapy followed by high-dose total lymphoid irradiation.

From January 1980 to September 1986, 50 patients with Hodgkin disease, clinical stages (CS) IIIB (26 cases) and IVB (24 cases) were treated by three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, followed by high-dose (40 Gy) (sub)total lymphoid irradiation, including the spleen. Ten patients (2 CS IIIB, 8 CS IVB) were in failure, and seven (4 CS IIIB, 3 CS IVB) died during their first complete remission (2 from treatment-related complications, 1 from unknown cause, 4 from insufficient supportive care and/or a shortage of health supplies); three patients (CS IIIB) relapsed (2 alive in second complete remission, 1 deceased). After 7 years, actuarial survival and relapse-free duration were, respectively, 64% for the 50 patients and 89% for the 40 patients in complete remission. Unfavourable outcome was observed in patients with pelvic nodal involvement. The low relapse rate (none in CS IVB) was the most striking result after brief chemotherapy followed by total lymphoid irradiation.