Mixed chimerism after allogeneic marrow transplantation.
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Biomedical subjects
Publications and source records attributed to D Scarpati.
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Twenty successive adult patients with lymphoblastic lymphoma entered a study of sequential chemotherapy consisting of an intensive LSA2-L2-type protocol to induce first complete remission. Twelve patients in first CR (median age 22 years, range 15-43), after receiving a conditioning regimen consisting of cyclophosphamide and total body irradiation, underwent autologous bone marrow transplantation. Of these 12 patients at diagnosis, one was in stage III and 11 in stage IV; 11 showed mediastinal and seven showed bone marrow involvement. The transplant procedure was well tolerated and no treatment-induced deaths occurred. At this time nine patients are alive and well 25-44 months post-transplant (median follow-up 36 months) with an actuarial disease-free survival of 75%. These early results suggest that high-dose chemoradiotherapy followed by autologous bone marrow transplantation may improve long-term disease-free survival in advanced stage adult lymphoblastic lymphoma. In order to draw definite conclusions, however, a larger and randomized study is needed.
Two different Total Body Irradiation (TBI) regimens were employed (1981 to July 1983) in Genoa in the conditioning program for the allogeneic Bone Marrow Transplantation (BMT) of 22 patients suffering from Acute Lymphoblastic Leukemia (ALL) in remission (7 patients in 1st remission, and 15 in 2nd remission). All patients were treated with Cyclophosphamide -60 mg/kg administered for two consecutive days (day -7 and -6)--and subsequently underwent fractionated TBI (days -3, -2, -1), that is, our conventional TBI regimen: 3.3 Gy/day per 3 days (total dose: 9.9 Gy). From August 1983 through 1988, 33 patients (14 in 1st remission and 19 in 2nd remission) were given 2 Gy twice a day, 6 hours apart, for 3 consecutive days (total dose: 12 Gy). Cyclosporine A was used for GvHD prophylaxis. At 58 months, out of the total figure of ALL patients in 2nd remission, 19% of those treated with 9.9 Gy/3 fr/3 days (fractionated TBI) is likely to be in remission, versus 65% of the cases treated with 12 Gy/6 fr/3 days (p less than 0.01) (hyperfractionated TBI); the actuarial overall survival is 23% after fractionated vs 60% after hyperfractionated TBI (p = 0.05). The incidence of idiopathic interstitial pneumonitis was very low (3.6%). Thus, we conclude that, in ALL patients in second remission, hyperfractionated TBI (12 Gy/6 fr/3 days) yields better results than fractionated TBI (9.9 Gy/3 fr/3 days), with lower relapse rate (33% vs 83%) and higher survival.
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Sixteen FIGO stage IIB-IV ovarian carcinoma patients who completed six to 12 courses of a cisplatinum-based combination chemotherapy and with minimal (less than 2 cm), microscopic, or no residual disease at second-look laparatomy received moving-strip abdomino-pelvic radiotherapy. Radiation treatment was feasible with acceptable toxicity; two patients had to interrupt therapy--one pretreated with 12 PAC courses because of WHO grade III leukopenia and the other because of grade III diarrhea. A third patient required surgery because of intestinal obstruction 1 month after cessation of radiotherapy. In patients with minimal residual disease at second look, the therapeutic value of sequential radiotherapy was unsatisfactory (five of six progressed), while further investigations were warranted in patients with no or microscopic residuum after second-look operation.
Thirty-four patients with advanced (stage IV) or relapsing squamous cell carcinoma of the head and neck (SCC-HN) were treated alternately with chemotherapy (CT) and radiotherapy (RT). Patients' characteristics were as follows: male: female ratio, 27:7; median age, 55 (34-76), median P.S., 1 (ECOG scale) (range 0-2). Patients studied had no renal, hepatic, or cardiac impairments, a life expectancy of greater than or equal to 3 months, and no previous treatment with RT or CT. Seventeen patients were previously untreated, and 17 had a relapse after radical surgery. The CT regimen consisted of 20 mg/m2 cisplatin, with 2 h forced diuresis, from day 1 to 5, and 200 mg/m2 i.v., from day 1 to 5, every 3 weeks, administered four times. The RT was performed after the first, second, and third CT course, and consisted of three courses of 20 Gy each, 2 Gy daily, 5 days per week. Weekend intervals were planned between CT and RT treatments. The 17 previously untreated patients showed an overall response rate of 88.2% [eight complete response (CR), seven partial response (PR), one stable disease (SD), one progression disease (PD)]; the 17 patients treated at relapse after radical surgery reached an overall response rate of 64.7% (six CR, five PR, six PD). Actuarial median survival is 47 weeks: 51 weeks in untreated patients, and 42 weeks in previously treated patients. Toxicity was mild, and only 10 patients suffered from grade III (WHO scale) gastrointestinal (2 patients), hematological (5 patients), mucosal (2 patients), and neurological (1 patient) toxicity. Neither grade IV toxicity nor treatment-related deaths have been observed. In our study, cisplatin and 5-FU alternating with RT has shown an interesting antitumor activity and moderate side effects.
A cooperative randomized study was begun in August 1983 to compare a sequential program of induction chemotherapy followed by definitive treatment, arm A, with an alternation of chemotherapy and radiotherapy (three courses of 20 Gy in ten daily fractions), arm B. The same chemotherapy was used in both arms: 6 mg/m2, vinblastine, hour 0; 30 mg, bleomycin, hour 6; 200 mg, methotrexate, hours 24 to 26; 45 mg, leucovorin, hour 48. One hundred sixteen patients entered the study, 55 in arm A and 61 in arm B. The patients all had previously untreated squamous cell carcinoma of the head and neck (SCCHN). Forty-five patients had stage III and 71 had stage IV disease. The two arms were fully comparable. As of April 1986, 116 patients were evaluable for survival, while 112 were evaluable for toxicity and 105 for response. Response analysis shows that there were 14 complete responses (CR) and 11 partial responses (PR), for an overall response rate (ORR) of 52% in arm A, and 30 CRs and seven PRs, for an ORR of 64.9% in arm B. The difference in terms of CR between the two arms was statistically significant (P less than .03). Progression-free survival (PFS) was also statistically different, with an advantage for arm B (P less than .05), but without differences in overall survival. Arm B correlates with a significant increase in mucositis compared with arm A (P less than .001).
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Between 1983 and 1986, a multicenter randomized study was conducted to compare a sequential program of induction chemotherapy (CT) followed by radiotherapy (RT), Arm A, with an alternation of 4 cycles of CT with 3 courses of RT (20 Gy/10 fractions up to a total dose of 60 Gy), Arm B, in advanced head and neck cancer patients. The same CT (VBM: Vinblastine, Bleomycin, Methotrexate) was used on both arms; one hundred and sixteen patients (pts) entered the study, 55 in Arm A, 61 in Arm B. Fourty-five pts had stage III and 71 stage IV cancers. The two arms are fully comparable. Up to October 1987, 116 pts are evaluable for survival, while 112 are evaluable for toxicity and 105 for response. In 21 patients (10 in Arm A, 11 in B) the association CT-RT was followed by surgery. Response analysis shows 14 complete responses in Arm A and 30 in Arm B (p less than or equal to 0.03). The median disease-free survival and median overall survival are also statistically different, with an advantage for Arm B (33 vs 22 weeks, p less than or equal to 0.0007, and 59 vs 38 weeks, p less than 0.03 respectively). The actuarial overall survival of complete responders at 50 months is 43% (B) and 21% (A). Toxicity (mainly stage III-IV mucositis) is superior in Arm B (30% vs 4%). Our experience demonstrates the advantages of alternate over sequential CT-RT. A comparison of this cyclic association with RT alone is in progress.
Sixteen patients affected by epidermoid carcinoma of the anal canal were treated preoperatively by means of an i.v. infusion of mitomycin C (15 mg/m2) on day 1 and 5-fluorouracil (750 mg/m2) days 1 to 5, followed by radiotherapy (3000 R in 3 weeks). Four to 6 weeks after the end of radiotherapy the response to the preoperative treatment was evaluated by means of biopsy. A reduction of the neoplastic mass was observed in 13 of the 16 patients. An evident correlation exists between the stage of the tumor and 1) the response to preoperative treatment, 2) local recurrence, and 3) long-term survival. In fact: 3/4 T1 patients reached a complete response (CR), and 1/4 T1, 5/5 T2 and 4/7 T3 patients achieved a partial response (PR); only 3/7 T3 patients never responded to preoperative treatment. After the initial surgery, only T2 (3/5) and T3 (4/7) patients underwent a second operation for a recurrence. Overall survival at 42 months was 62.5% (T1, 100%; T2, 80%; T3, 28.5%).
From january 1984 to may 1986, 31 patients, 15 ANLL, 8 ALL (in remission status) and 8 NHL (6 in remission, 2 in relapse) have been treated with chemo-radiotherapy [cyclophosphamide 60 mg/kg X 2 days + total body irradiation (TBI): 10 Gy/1 fr. in ANLL and NHL patients, 12 Gy/3 fr./3 days with 4 Gy boost testicular dose in ALL] and autologous bone marrow transplantation (BMT). Seventeen patients are alive, 16 in remission: 9 (60%) ANLL, 2 (25%) ALL, 5 (62%) NHL (median 8+ months, follow up 1+/29+); 2 patients presented interstitial pneumonitis (6.45%). In this series, very good results have been achieved in ANLL, where no relapse was noted, encouraging achievements in NHL, with 2/6 relapses; unsatisfactory results in ALL, with 4/8 relapse. Advantages and disadvantages of autologous relative to allogenic BMT, and of conditioning regimen with or without TBI are discussed.
Advanced neuroblastoma, scarcely responsive to conventional therapies, can take advantage of high dose chemio-radiotherapic treatment followed by bone marrow transplant. Nineteen young patients underwent an ablative chemotherapy with high dose Vincristine and Melphalan plus Total Body Irradiation in Genoa, Italy; all of them underwent autologous bone marrow transplantation. Fourteen children were in complete remission (CR), 5 had residual disease. Thirteen are alive after a median of 7 months following transplant; 9 are in CR; 4 have disease; 1 died for toxicity; 5 for relapse. The results seem to suggest that ablative therapy should be given to patients in CR. Toxicity was not remarkable mainly as far as TBI is concerned.
Non-functioning parathyroid carcinoma is a very rare disease. Only 12 cases have been reported in the literature. The clinical behavior is characterized by the appearance and growth of a neck mass or nodule, which often has been present for many years, and is not accompanied by clinical or laboratory evidence of hypercalcemia or elevated levels of parathyroid hormone (PTH) in peripheral blood. Pathologic findings are similar to those of functioning tumors, and the proof of malignancy is established on the basis of an increased mitotic index only. Data on survival from cases reported in the literature are not conclusive; however, the non-functioning type of parathyroid carcinoma seems to be a more aggressive disease. Radiotherapy seems to be effective in the local control of the disease, but most patients become metastatic. Even if no data are available on response to chemotherapy, the course of the disease is relatively indolent.
20 patients with acute nonlymphoid leukemia (ANLL) in first remission were given cyclophosphamide, 120 mg/kg, followed by total body irradiation (TBI) and an HLA-identical allogeneic marrow transplant (BMT). TBI was delivered in a single dose (10 Gy on day -1) in 2 patients, or in fractionated doses (3.3 rad/day on days -3, -2, -1) in 18 patients. The median age of patients was 22 years (range 2-44). Median time from remission to BMT was 5 months (range 1-12). 5 patients died of transplant-related toxicity (graft-versus-host disease with or without interstitial pneumonia) and 15 are alive 7-77 months post-BMT (median 20). The actuarial 72 months survival is 73%. There has been one relapse in a 2-year-old child, 4 months post-BMT, in the marrow and in the testis. The 72-month actuarial disease-free survival is 68%. The actuarial probability of relapse is 7%. This study indicates that a high proportion of ANLL patients treated in first remission with fractionated TBI and allogeneic marrow transplantation can become long-term disease-free survivors.
The authors report a case of an 85-year-old patient suffering from perianal Paget's disease treated with polychemotherapy and radiotherapy, and followed for 30 months with no evidence of recurrence. Such treatment may be an effective alternative to surgical resection in elderly patients, although no definitive conclusion can be drawn due to the rarity of the disease.
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The Authors suggest a simple, inexpensive and accurate method to evaluate the sigmoid and rectal radiodoses delivered by brachitherapy in the treatment of cervical neoplasia.
The authors evaluate the reliability of computed axial tomography in the staging of cervical cancer. This technique, neither invasive nor dangerous for the patient allowed to define better the involvement of perirectal fat tissue and of the external layer of the rectal wall. On the other hand it has some limits, in particular it is aspecific and unable to define exactly morphological changes of lymph-nodes and other structures.