Cancer of the esophagus following allogeneic bone marrow transplantation for acute leukemia.

The successful development of allogeneic bone marrow transplantation (BMT) has markedly improved the treatment results for acute leukemia and other hematologic diseases. However, significant complications are associated with this procedure including the development of chronic graft versus host disease (GVHD). Treatment for this condition requires chronic immunosuppression which can lead to the development of second cancers. It is well known that immunosuppression is associated with a variety of tumors, most commonly lymphoma. The development of solid tumors appears to be less common but follow-up studies of patients treated for Hodgkin's disease demonstrate a rising incidence of solid tumor development after a delay of 5 to 10 years. We describe a patient recently treated for a squamous cell carcinoma of the esophagus which developed 5 years after an allogeneic BMT for acute myelogenous leukemia (AML). The patient had been treated with immunosuppressants for chronic GVHD. The clinical course is described and the literature is reviewed regarding recent experience with the development of solid tumors following allogeneic BMT. The majority of second tumors following BMT are lymphomas and leukemias. Secondary solid tumors are less common, but the incidence appears to increase over time. Squamous carcinomas are most common and a preparative regimen combining radiation and chemotherapy may increase risk. Careful long-term follow-up of BMT is essential in order to detect second tumors at an early stage.

An unusual extramedullary relapse of acute nonlymphocytic leukemia after allogeneic bone marrow transplantation.

Recurrent leukemia following allogeneic bone marrow transplantation (BMT) for acute nonlymphocytic leukemia (ANLL) continues to be a cause of morbidity and mortality. Most relapses occur within the first 6-12 months, although disease-free survival curves do not begin to plateau until 24 months posttransplant. The majority of relapses occur in the bone marrow. Extramedullary relapses usually occur in "sequestered sites," i.e., the testis and central nervous system. Although the true incidence of extramedullary relapse in "nonsequestered" sites after allogeneic BMT for ANLL is unknown, it appears that this type of relapse is distinctly unusual. The authors present a case of an unusual extramedullary relapse of ANLL in the breast at day +613 after allogeneic BMT for ANLL. In addition, we briefly review the English BMT literature and discuss the differential diagnosis of breast masses in women who survive allogeneic BMT for ANLL.

Mediastinal involvement in adults with lymphoblastic lymphoma.

Radiologic, clinical, and pathologic findings are described in 6 young adults with lymphoblastic lymphoma (LBL), an aggressive tumor which has recently become recognized as a serious threat to adults as well as to children. Each patient presented with a mediastinal mass, three of them developing cardiac tamponade and one a superior vena cava syndrome. CT scanning and echocardiography were particularly helpful in defining the lesions. The rapid dissemination of LBL, and its early progression to a leukemic phase call for prompt diagnosis and treatment.

ICRF-159 (razoxane) in patients with advanced squamous cell carcinoma of the uterine cervix. For the Gynecologic Oncology Group.

Thirty-one patients with advanced squamous cell carcinoma of the cervix were entered onto this phase II study evaluating the efficacy of ICRF-159 (razoxane). Three of these patients were excluded; one had no tumor, one had a second primary, and one received no therapy. ICRF-159 was administered orally at a dose of 2.5 g/m2 weekly until progression, unacceptable toxicity, or death. Adverse effects were primarily hematologic in nature. Twenty-three of the 28 patients exhibited leukopenia which in ten instances was severe (below 2000/mm3). Seven cases had thrombocytopenia (one case below 50,000/mm3). Other toxicity, including fever and anorexia, was mild to moderate. There was tumor response in five (18%) patients (one CR, four PRs) ranging from 1 to 5 months. Fifteen patients with stable disease and eight with progressive disease had a median survival duration of 3.8+ and 3.5+ months, respectively. ICRF-159 showed limited activity in this patient population. However, it might be considered for combination with other low myelosuppressive agents.

4'-(9-acridinylamino)methane-sulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA) in the treatment of relapsed adult acute leukemia.

Between March 1980 and December 1981, 22 patients were treated with 4'(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA), each given by I.V. push in a dosage of 150 mg/m2 for 5 days. Seven of 12 prior-remitting, acute nonlymphoblastic leukemia (ANLL) patients achieved complete remission (58%). Six ANLL patients who failed to remit on standard daunorubicin-cytosine arabinoside programs also failed to remit on the m-AMSA-AZA combination. Two patients with relapsed acute lymphatic leukemia (ALL) also failed while two patients with chronic myelocytic leukemia (CML) in evolution were cytoreduced. The seven patients who achieved remission had additional relapse-free survival for a median of six months (range 1-23+ months). One patient obtained a second remission with m-AMSA-AZA after relapse which followed a 9-month period of nonmaintained remission. Most patients demonstrated mild to moderate nausea and vomiting. Hepatic toxicity was mild to infrequent. Only four patients showed cardiac toxicity which was not life-threatening. The most troublesome toxicity was mucositis and was seen in 11 patients; four whom required I.V. hyperalimentation. We conclude that this combination is an effective salvage program for relapsed prior-remitting ANLL. Future studies should be conducted in three areas. The first study might be a comparison of relapsed prior-remitting ANLL with single-agent m-AMSA. The second, in untreated ANLL, following induction with DAT, might use m-AMSA-AZA in consolidation and maintenance arms of future protocols. The final study should explore m-AMSA-AZA activity in evolved CML in a greater number of patients.

Dibromodulcitol in the treatment of metastatic hemangiopericytoma.

Hemangiopericytoma is an uncommon sarcoma arising from the pericapillary cells. While the rarity of this lesion precludes randomized investigation, metastatic hemangiopericytoma has been noted to respond to a variety of agents, including vincristine, adriamycin, actinomycin, and high-dose methotrexate. We wish to report an unusual case of this disease which failed to respond to the above but then exhibited a marked response to dibromodulcitol. In light of the unusual nature of this response, we would like to suggest a controlled trial of the use of dibromodulcitol in patients with this rare tumor.

Malignant paraganglioma of retroperitoneum. Light, electron microscopic and ultrasonographic study.

A malignant retroperitoneal nonchromaffin paraganglioma in a thirty-four-year-old man was studied by light and electron microscopy. Histologically, the tumor cells displayed a tendency to surround granular, eosinophilic intercellular material and to form nests and pseudo-acini. Ultrastructurally, the tumor was composed of moderately well-differentiated epithelial cells intermixed with sparse sustentacular cells. An organoid pattern, reminiscent of the functional anatomic unit of nonchromaffin paraganglia, was seen occasionally. Epithelial cells formed pseudo-acini around dilated microvillous processes. These morphologic features are consistent with the neurocrestal origin of paragangliomas. The patient died ten months after presentation despite an initial favorable response to irradiation.

Chemotherapy of advanced measurable colon and rectal carcinoma with oral 5-fluorouracil, alone or in combination with cyclophosphamide or 6-thioguanine, with intravenous 5-fluorouracil or beta-2'-deoxythioguanosine or with oral 3(4-methyl-cyclohexyl)-1(2-chlorethyl)-1-nitrosourea: a Phase II-III study of the Eastern Cooperative Oncology Group (EST 4273).

In a randomized multi-institutional trial of the Eastern Cooperative Oncology Group, 316 patients with advanced measurable colorectal adenocarcinoma were treated with a weekly schedule of 5-fluorouracil given orally and intravenously with oral-5-fluorouracil in combination with cyclophosphamide or 6-thioguanine, or with oral Methyl CCNU administered once every eight weeks. On failure or progression, 133 protocol patients crossed-over to a secondary therapy, while 116 other patients previously treated with 5-fluorouracil off protocol were randomized to treatment with Methyl CCNU or B-2'-deoxythioguanosine. Response rates among patients who had received no prior chemotherapy were 18% to oral 5-FU, 15% to intravenous 5-FU and to MeCCNU, 12% to 5-FU and 6-thioguanine and 5% to cyclophosphamide and 5-FU, with little activity (3% response rate) in crossover or previously treated patients. Treatment with 5-FU, particularly oral 5-FU was associated with the least drug-related toxicity. Hematologic toxicity was greatest with Methyl CCNU, but was no more frequent in previously treated than in untreated patients. A tendency toward cumulative bone marrow depression was noted. 5-FU was effective only in ambulatory patients, whereas responses among non-ambulatory patients were seen only in the group treated with Methyl-CCNU.

Low dose bleomycin and methotrexate in cervical cancer.

Twenty patients with recurrent and disseminated carcinoma of the cervix were treated with Bleomycin, 10 mg/m2 weekly and Methotrexate, 10 mg/m2 every fourth day. Twelve of the 20 (60%) had a greater than 50% shrinking of measured tumor masses lasting a median remission time of 7.5 months. The data suggest that combination protracted chemotherapy with these drugs of metastatic cervical cancer might improve the outlook of patients with this condition.