Adult acute lymphoblastic leukemia: results of the Iowa HOP-L protocol.

Fifty-nine consecutive previously untreated adult patients with acute lymphoblastic leukemia (ALL) were entered onto a prospective single-arm trial of doxorubicin, vincristine, prednisone, and asparaginase (HOP-L) induction therapy followed by CNS prophylaxis and 3 years of maintenance therapy. Consolidation therapy was not administered. The study population included a large number of older (greater than 50 years) patients. Seventy-five percent of patients achieved complete remission. With a median follow-up of 6 years, the median duration of complete remission is greater than 4 years, with 53% of patients expected to remain in remission at both 3 and 5 years. Overall, median survival duration is 27.9 months, with 45% and 35% of all patients expected to survive 3 and 5 years, respectively. Multivariate analysis identified patients with T-cell disease and mediastinal masses (P less than .001) and those with low values of lactic dehydrogenase (LDH) (P = .057) as being at greatest risk of relapse. Therapy was well tolerated by patients under age 35, but older patients suffered appreciable mortality. We conclude that this treatment program is effective therapy for adult ALL, yielding a large proportion of durable remissions despite the exclusion of consolidation therapy.

Chemotherapy in patients who fail radiotherapy for diffuse aggressive non-Hodgkin's lymphoma.

Twenty patients with diffuse aggressive non-Hodgkin's lymphoma were treated primarily with radiotherapy for localized disease and had subsequent disease progression. All 20 patients then received an adriamycin based, combination chemotherapy regimen, but only seven patients (35%) achieved a complete remission, and only four patients (20%) currently remain in remission. When 15 patients treated with the CHOP regimen were compared to 62 patients treated with CHOP during the same time period but who did not have preceding radiotherapy, patients with previous radiotherapy had a lower complete remission rate (i.e. 66% versus 33%) and a slightly lower 5-year survival rate (i.e. 41% versus 20%). Thus, unlike patients with Hodgkin's disease, patients with diffuse aggressive non-Hodgkin's lymphomas who fail radiotherapy for localized disease might not have an especially good outlook with subsequent chemotherapy.

The significance of radiotherapy treatment duration in intracranial ependymoma.

PURPOSE: To determine if radiation therapy treatment duration has an impact on the outcome of intracranial ependymoma. METHODS AND MATERIALS: From 1965 to 1997, 34 patients with intracranial ependymoma were seen and treated with postoperative radiotherapy (RT). There were 26 male and 8 female patients with a median age of 14 years (range, 18 months to 60 years). Tumor location was infratentorial in 23 (67.6%) and supratentorial in 11 (32.4%). Pathology was low-grade in 25 (73.5%) and high-grade in 9 (26.5%). Two (5.9%) patients had M+ disease at initial diagnosis. Gross total resection was achieved in 12 (35.3%), subtotal resection in 19 (55. 9%), and biopsy alone in 3 (8.8%). Median RT dose to the primary site was 5400 cGy (range, 4500 cGy to 6600 cGy). The entire neuraxis was treated in 14 (41.2%), whole brain in 9 (26.5%), and the primary site alone in 11 (32.4%). Median radiotherapy treatment duration was 43 days (range, 26 to 122 days). Patients treated with craniospinal RT were more likely to have treatment duration of > or =50 days. Median follow-up was 108 months (range, 24 to 252 months). RESULTS: The 5-, 10-, and 15-year overall survival rates were 71.5%, 63.3%, and 55.4%. Local control rates at 5, 10, and 15 years were 61.8%, 57.7%, and 57.7%. For patients with RT treatment duration <50 days, the 5-, 10-, and 15-year overall survivals were 85.5%, 78.9%, and 65.7% whereas for those with treatment duration > or = 50 days, the corresponding rates were 45.5%, 36.4%, and 36.4% (p = 0.01, log-rank test). Local control rate at 5, 10, and 15 years was 70.6% for patients with RT treatment duration <50 days and 45.5%, 36.4%, and 36.4% for patients with RT treatment duration > or =50 days (p = 0.05, log-rank test). Age, gender, tumor location, tumor grade, degree of surgical resection, RT volume, and RT dose (4500-5399 cGy vs. 5400-6600 cGy) were not found to have a statistically significant impact on overall survival, disease-free survival, or local control. The most common site of failure was local, found in 13 (38.2%) patients. Three patients also had spinal failure in addition to a primary site failure. There were no isolated nonprimary site brain or spine failures. CONCLUSIONS: Radiation therapy treatment duration is an important prognostic factor for survival and local control with patients having treatment duration <50 days having a better outcome than those with treatment duration > or =50 days. Because the overwhelming site of failure was local, we recommend local field irradiation in patients with M0 disease.

Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma.

PURPOSE: To examine the long-term effects of treatment in children receiving radiotherapy for head and neck rhabdomyosarcoma. METHODS: From 1967 to 1994, a total of 30 children with head and neck rhabdomyosarcoma received megavoltage radiotherapy at one institution. Seventeen patients (57%) have survived and have at least a 5-year follow-up. There were 11 males and 6 females, with a median age of 5.7 years (range 2.2-11.6) at the time of radiotherapy. Tumor location was orbit in 6 patients, infratemporal fossa in 4, paranasal sinuses in 2, and supraglottic larynx in 2; the nasopharynx, pterygopalatine fossa, and parotid gland were sites for the remaining children. All but 2 patients had tumors of embryonal histology. The Intergroup Rhabdomyosarcoma Study (IRS) Group was I in 2, II in 3, and III in 11 children; 1 patient had a recurrent tumor after surgery alone. Radiotherapy volume was the primary tumor or tumor bed in 13, tumor and whole brain in 3, and tumor and craniospinal axis in 1. Median radiotherapy dose to the primary site was 5,040 cGy (range 4,140-6,500) and to the whole brain was 3,000 cGy. All but 1 were treated with 150-200-cGy fractions; 1 patient received 250-cGy fractions for a tumor in the larynx. Chemotherapy was vincristine (V), actinomycin-D (A), and cyclophosphamide (C) in 10 patients, VAC + adriamycin in 2, VA in 1, VA + ifosfamide in 1, VC + adriamycin in 1, and none in 2. One patient had salvage chemotherapy consisting of cisplatin and etoposide. Median follow-up time was 20 years (range 7.5-33). RESULTS: Late effects of treatment were seen in all patients and included facial growth retardation in 11, neuroendocrine dysfunction in 9, visual/orbital problems in 9, dental abnormalities in 7, hearing loss in 6, and hypothyroidism in 3. Intellectual and academic delays were documented in 3 patients who had received whole brain radiotherapy. While neuroendocrine, thyroid, dental, and cognitive sequelae were primarily attributed to radiotherapy, hearing loss was thought to be a direct result of tumor destruction and, in 1 case, cisplatin chemotherapy. Late effects at or beyond 10 years from radiotherapy were few, but severe, and included chondronecrosis, esophageal stenosis, second malignancy, and brain hemorrhage. CONCLUSION: Late effects of treatment in children receiving radiotherapy for head and neck rhabdomyosarcoma are frequent. Although radiotherapy is a significant contributor of neuroendocrine, dental, thyroid, and cognitive toxicity, it is not usually implicated with hearing loss. Late toxicity of treatment beyond 10 years is not as frequent as those occurring within 10 years of therapy.

Chemodectoma of the temporal bone: a comparison of surgical and radiotherapeutic results.

Between January 1950 and December 1981, 32 patients with chemodectomas of the temporal bone were treated at the University of Iowa Hospitals and Clinics. Thirteen patients were treated with surgery alone, 15 with radiation therapy alone, one with preoperative radiation therapy and surgery, and three with surgery and postoperative radiation therapy. In general, the patients treated with radiotherapy alone or combined therapy (radiotherapy group) had more advanced tumors than those treated with surgery alone (surgery group). For the surgery group, the initial local control rate was 46% and the ultimate local control rate 84% following salvage with additional surgery, 31% developed complications, and 78% survived 10 years. For the radiotherapy group, 84% had local tumor control, 11% developed complications, and 77% survived 10 years. These results demonstrate that radiation therapy is an effective treatment modality for chemodectomas of the temporal bone.

Hemangiopericytoma--the role of radiotherapy.

Between 1955 and 1987, 15 patients with hemangiopericytomas were seen at the University of Iowa Hospitals and Clinics. Twelve of these were thought to have localized tumors and three had metastatic disease at diagnosis. Seven of the 12 patients with localized disease were treated with surgery alone, four were treated with surgery and postoperative radiation therapy, and one was treated with surgery and chemotherapy. Only one of the seven patients initially treated with surgery alone has remained continuously free of disease, although two others were salvaged with radiation therapy. In contrast, all four patients initially treated with surgery and postoperative radiation therapy have remained alive with no evidence of disease in spite of the fact that three of these patients had gross residual tumor at the time of irradiation. Ten patients received radiation therapy at some stage of their management. Local tumor control was achieved at all sites receiving greater than 5500 cGy. Six patients received chemotherapy sometime during the course of their management, although no complete or partial responses were observed. In this small series, mitotic activity was not an accurate predictor of biologic behavior.

Alopecia associated with unexpected leakage from electron cone.

Excessive irradiation due to unexpected leakage was found on a patient receiving electron beam therapy. The cause of this leakage was analyzed and the amount of leakage was measured for different electron beam energies. The highest leakage occurred with a 6 x 6 cm cone using a 12 MeV electron beam. The leakage dose measured along the side of the cone could be as great as 40%. Until the cones are modified or redesigned, it is advised that all patient setups be carefully reviewed to assure that no significant patient areas are in the side scatter region.

The role of radiation therapy in the management of ependymomas of the spinal cord.

Twenty patients with biopsy-proven ependymomas of the spinal cord were treated between 1960 and 1984-7 with surgery only, 3 with radiation therapy only, and 10 with surgery and postoperative radiation therapy. Of these, 2 patients developed recurrent tumor at the primary site, 3 developed a recurrent tumor in the thecal sac, and 1 developed distant metastasis. The absolute 5- and 10-year survival rates were 95% (19/20) and 86% (12/14), respectively. None of 13 patients who were treated with radiation therapy only or combined surgery and postoperative radiation therapy developed recurrent tumor at the primary site, and none of 7 patients who received thecal sac irradiation developed thecal sac recurrences. In contrast, 2 of 7 patients (29%) treated with surgery alone developed recurrent tumor at the primary site, and 3 of 13 patients (23%) who received no thecal sac irradiation developed a recurrent tumor in the thecal sac. The failure rates following surgery were greatest in patients who had tumor removed in a piecemeal fashion (43%, 6/14). The results show that radiation therapy is probably not necessary if the tumor has been removed completely in an en bloc fashion. However, radiation therapy is needed if the tumor has been incompletely removed or removed in a piecemeal fashion. If the tumor has been removed in a piecemeal fashion, the radiation portals should be extended to include the thecal sac. Histologic subtypes influenced the pattern of recurrence. Myxopapillary ependymomas and high grade cellular ependymomas appear to be more likely to recur in the thecal sac. However, no big difference could be detected in local recurrence.

A comparison of the roles of surgery and radiation therapy in the management of carcinoma of the female urethra.

Between 1939 and 1986, 42 patients with carcinoma of the female urethra were treated with surgery and/or radiation therapy at the University of Iowa. Ten patients were treated with surgery alone, 28 with radiation therapy alone, and 4 with combined surgery and radiation therapy. Seventeen patients (40%) developed persistent or recurrent disease at the primary site and 15 (36%) had failures in the inguinal nodes. The actuarial 5-year survival rate was 33.5%. Only 36% (10/28) of patients treated with radiation therapy had local failures, compared to 60% (6/10) of those treated with surgery alone. The best results were achieved with combined interstitial and external beam irradiation. Whereas 57% (8/14) of patients who were treated with combined interstitial and external beam irradiation were alive NED at 3 years, none of 7 patients (0%) treated with interstitial implants only and 2 of 7 patients (29%) treated with external beam irradiation alone were alive NED at 3 years. There was a significantly lower inguinal failure rate in patients who received treatment to the inguinal nodes (10%) than in those who did not receive inguinal area treatment (52%), and this translated into a superior 5-year survival for those patients (60% vs 18%). Survival rates did not correlate with histopathologic type in this series, although there were differences in the patterns of failure. Survival rates did correlate well with clinical stage.

Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes.

Forty-three patients were treated with extended field irradiation for periaortic metastasis from carcinoma of the uterine cervix (FIGO stages IB-IV). Twelve patients (28%) remained continuously free of disease to the time of analysis or death from intercurrent disease, 20 (46%) had persistent cancer within the pelvis, 11 (26%) had persistent periaortic disease, and 23 (53%) developed distant metastasis. The actuarial 5-year survival rate was 32%. The results correlated well with the periaortic tumor burden at the time of irradiation. None of 19 patients (0%) with microscopic or small (less than 2 cm) periaortic disease had periaortic failures, compared to 29% (4/14) of those with moderate-sized (2-5 cm) disease and 70% (7/10) of those with massive (greater than 5 cm) periaortic metastasis. Similarly, the 5-year survival rates were 50% (6/12) with microscopic disease, 33% (2/6) with small gross disease, 23% (3/13) with moderate-sized disease, and 0% (0/10) with massive periaortic metastases. Only 10% (1/10) of patients whose tumor extended to the L1-2 level survived 5 years, compared with 31% (9/29) of those whose disease extended no higher than the L3-4 level. The periaortic failure rates correlated to some extent with the dose delivered through extended fields, although the difference was not statistically significant. Only 8% (1/13) of those who had undergone extraperitoneal lymphadenectomies developed small bowel complications, compared with 25% (7/29) of those who had had transperitoneal lymphadenectomies. The incidence of small bowel obstruction was 8% (1/13) following periaortic doses of 4000-4500 cGy, 10% (1/10) after 5000 cGy, and 32% (6/19) after approximately 5500 cGy. From this, we concluded that the subset of patients who would benefit most from extended field irradiation are those in whom the residual disease in the periaortic area measures less than 2 cm in size at the time of treatment, whose disease extends no higher than L3, and whose cancer within the pelvis has a reasonable chance of control with standard radiation therapy techniques.

Late effects in children treated with radiation therapy for Wilms' tumor.

PURPOSE: To determine the frequency and types of late effects in children receiving radiation therapy (RT) for Wilms' tumor. MATERIALS AND METHODS: From 1968 to 1994, 55 children received megavoltage RT at our institution as part of treatment for Wilms' tumor. A total of 42 (76.4%) have survived and have a minimum follow-up of 5 years. There were 25 female and 17 male patients with a median age at diagnosis of 48 months (range, 7-126 months). There were 12 Stage I, eight Stage II, 15 Stage III, six Stage IV, and one Stage V patient. RT was delivered to the hemiabdomen in 36 and whole abdomen in six patients. RT dose was 1000-1200 cGy (Group A) in 12, 1201-2399 cGy (Group B) in 11, and 2400-4000 cGy (Group C) in 19. Whole-lung RT was delivered to 13 patients either at diagnosis or pulmonary relapse. All patients received chemotherapy; the most common agents were actinomycin-D/vincristine/adriamycin in 13 and actinomycin-D/vincristine in 18. Median follow-up was 181 months (range, 60-306 months). RESULTS: Of 42 patients, 13 (31.0%) did not have late effects of treatment. The number of patients who developed muscular hypoplasia, limb length inequality, kyphosis, and iliac wing hypoplasia were seven (16.7%), five (11.9%), three (7.1%), and three (7.1%), respectively. Scoliosis was seen in 18 (42.9%) with only one patient requiring orthopedic intervention. Median time to development of scoliosis was 102 months, with a range of 16-146 months. The actuarial incidence of scoliosis at 5, 10, and 15 years after RT was 4.8 +/- 3.3%, 51.8 +/- 9.0%, and 56.7 +/- 9.3%, respectively. Only one of 12 Group A patients developed scoliosis. The 10- and 15-year actuarial incidences of scoliosis for Group A and B patients were 37.7 +/- 12.4% and 37.7 +/- 12.4%, whereas for Group C patients the incidences were 65.8 +/- 12.0% and 74.4 +/- 11. 7% (p = 0.03, log rank test). The actuarial incidence of bowel obstruction at 5, 10, and 15 years was 9.5 +/- 4.5%, 13.0 +/- 5.6%, and 17.0 +/- 6.5%. Of 23 patients, five irradiated within 10 days of surgery and one of 19 irradiated after 10 days developed bowel obstruction (p = 0.09, log rank test). Three patients developed hypertension with normal blood urea nitrogen (BUN) and creatinine levels; another patient had chronic renal insufficiency in a nonirradiated kidney. One patient developed diffuse interstitial pneumonitis. Of the 19 female patients who have reached puberty, three have given birth, and 15 have regular and one has irregular menstrual periods. Four patients developed benign neoplasms; three were in the RT field (two osteochondroma, one lipoma) and one outside (cervical intraepithelial neoplasia II). There were three second malignancies (chronic myelogenous leukemia at 9 years, osteosarcoma at 11 years, and breast cancer at 25 years after initial diagnosis of nephroblastoma); both solid malignancies occurred in the RT field. CONCLUSIONS: Late effects of therapy were seen in more than two thirds of children treated for Wilms' tumor. Children treated with lower doses (<2400 cGy) had a lower incidence of scoliosis compared with those who received more than 2400 cGy. There is also a suggestion that the incidence is lower in patients who received 1000-1200 cGy. Severe physical and functional deformity from RT was uncommon.

Preliminary results of a pilot study of pentoxifylline in the treatment of late radiation soft tissue necrosis.

Between September 1988 and August 1989, 12 patients with 15 sites of late radiation necrosis of the soft tissues were treated with pentoxifylline, a hemorrheologic agent that has been used to treat a variety of vasculo-occlusive disorders. Four of these necroses were located in the oromucosa, four in the mucosa of the female genitalia, and seven in the skin. At the time of analysis, 87% (13/15) of the necroses had healed completely, and one was partially healed. Furthermore, the time-course of healing with pentoxifylline was significantly less than the duration of nonhealing prior to pentoxifylline (average: 9 weeks vs 30 1/2 weeks). All patients had pain relief. These results indicate that pentoxifylline can contribute to the healing of soft tissue radiation necrosis. They also support the concept that late radiation injury in skin and mucosa is at least partly due to vascular injury.

The role of kilovoltage irradiation in the treatment of keloids.

This is a retrospective analysis of the results of kilovoltage irradiation given to prevent the regrowth of 203 keloids excised at the University of Iowa Hospitals and Clinics, Iowa City, Iowa, Lutheran Hospital in Moline, Illinois, and Mercy Hospital in Cedar Rapids, Iowa. We found that a minimum follow-up of 1 year is needed to evaluate the results of post-excisional kilovoltage x-ray therapy. A dose versus response effect was also observed. Although it is desirable to use the lowest possible dose of radiation that is likely to be effective, the likelihood of failure is too great to justify the routine use of doses of less than 900 cGy regardless of how they are fractionated or when they are given. It appears that the total dose of irradiation that is given to prevent the regrowth of an excised keloid is more important than when irradiation is started, the size of the largest fraction given, whether the irradiation is completed in 1 week or 3, or where the keloid has grown. When a small number of keloids were irradiated less than 1 year after they first appeared greater than or equal to 1500 cGy were sufficient to control 90% of them without re-excision.

A comparison of the roles of surgery and radiation therapy in the management of craniopharyngiomas.

Fifty-two patients with craniopharyngioma were seen between January 1961 and July 1986. Of these, 40 were treated with surgery alone, 8 with surgery and postoperative radiotherapy, and 3 with radiotherapy alone. One patient received no treatment. For the group treated with surgery alone, 33% (13/40) had local tumor control, 42.5% (17/40) developed major complications, and 71% (25/35) survived 5 years. With surgery and postoperative radiotherapy, 100% (8/8) had local tumor control, 25% (2/8) developed major complications, and 100% (7/7) survived 5 years. Two of the three patients treated with radiotherapy alone had local tumor control and the third was salvaged with surgery. The "complete resection" rate for 32 patients treated with radical surgery was 63% (20/32). Tumor control was achieved in 50% (10/20) of the patients treated with "complete resection" without radiotherapy, in 15% (3/20) of the patients treated with "incomplete resection" without radiotherapy, and in 100% (8/8) of the patients treated with "incomplete resection" and postoperative radiotherapy. In this series, doses of 5000-5500 cGy were as effective in achieving control as 5500-6000 or 6000-7000 cGy.

Usefulness of tumor volumetry by magnetic resonance imaging in assessing response to radiation therapy in carcinoma of the uterine cervix.

PURPOSE: Clinical evaluation of tumor size in cervical cancer is often difficult, and clinical signs of radiation therapy failure may not be present until well after completion of treatment. The purpose of this study is to investigate early indicators of treatment response using magnetic resonance (MR) imaging for quantitative assessment of tumor volume and tumor regression rate before, during, and after radiation therapy. METHODS AND MATERIALS: Thirty-four patients with cervical cancer Stages IB [5], IIB [8], IIIA [1], IIIB [14], IVA [3], IVB [1], and recurrent [2] were studied prospectively with four serial MR examinations obtained at the start of radiation therapy, at 2-2.5 weeks (20-24 Gy), at 4-5 weeks (40-50 Gy), and 1-2 months after treatment completion. Tumor volume was assessed by three-dimensional volumetric measurements using T2-weighted images of each MR examination. The volume regression rate was generated based on the four sequential MR studies. These findings were correlated with local control, metastasis rate, and disease-free survival. Median follow-up was 18 months (range: 9-43 months). RESULTS: The tumor regression rate after a dose of 40-50 Gy correlated significantly with treatment outcome. The actuarial 2-year disease-free survival was 88.4% in patients with tumors regressing to < 20% of the initial volume compared with 45.4% in those with > or = 20% residual (p = 0.007). The incidence of local recurrence was 9.5% (2 out of 21) and 76.9% (10 out of 13), respectively (p < 0.001). Analysis by initial tumor volume showed that this observation was valid in patients with initial volumes between 40 and 100 cm3. Analysis by FIGO stage confirmed this observation in all patients except those with Stage IB. CONCLUSION: Sequential tumor volumetry using MR imaging appears to be a sensitive measure of the responsiveness of cervical cancer to irradiation. Treatment response can be assessed as early as during the course of radiation therapy by measurement of initial tumor volume and regression rate at 40-50 Gy. In patients with large (> 40 cm3) and advanced (Stage > or = IIIA) tumors, this technique may be helpful in supplementing the clinical examination for response assessment. The identification of patients at high risk for treatment failure may ultimately lead to improved clinical outcome.

Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay.

PURPOSE: This study investigated sequential changes in tumor blood supply using magnetic resonance (MR) perfusion imaging and assessed their significance in the prediction of outcome of patients with advanced cervical cancer. The purpose of this project was to devise a simple, noninvasive method to predict early signs of treatment failure in advanced cervical cancer treated with conventional radiation therapy. METHODS AND MATERIALS: Sixty-eight MR perfusion studies were performed prospectively in 17 patients with squamous carcinomas (14) and adenocarcinomas (3) of the cervix, Stages bulky IB (1), IIB (5), IIIA (1), IIIB (8), and IVA (1), and recurrent (1). Four sequential studies were obtained in each patient: immediately before radiation therapy (pretherapy), after a dose of 20-22 Gy/ approximately 2 weeks (early therapy), after a dose of 40-45 Gy/ approximately 4-5 weeks (midtherapy), and 4-6 weeks after completion of therapy (follow-up). Perfusion imaging of the tumor was obtained at 3-s intervals in the sagittal plane. A bolus of 0.1 mmol/kg of MR contrast material (gadoteridol) was injected intravenously 30 s after beginning image acquisition at a rate of 9 ml/s using a power injector. Time/signal-intensity curves to reflect the onset, slope, and relative signal intensity (rSI) of contrast enhancement in the tumor region were generated. Median follow-up was 8 months (range 3-18 months). RESULTS: Tumors with a higher tissue perfusion (rSI > or = 2.8) in the pretherapy and early therapy (20-22 Gy) studies had a lower incidence of local recurrence than those with a rSI of < 2.8, but this was not statistically significant (13% vs. 67%; p = 0.05). An increase in tumor perfusion early during therapy (20-22 Gy), particularly to an rSI of > or = 2.8, was the strongest predictor of local recurrence (0% vs. 78%; p = 0.002). However, pelvic examination during early therapy (20-22 Gy) commonly showed no appreciable tumor regression. The slope of the time/signal-intensity curve obtained before and during radiation therapy also correlated with local recurrence. Follow-up perfusion studies did not provide information to predict recurrence. CONCLUSION: These preliminary results suggest that two simple MR perfusion studies before and early in therapy can offer important information on treatment outcome within the first 2 weeks of radiation therapy before response is evident by clinical examination. High tumor perfusion before therapy and increasing or persistent high perfusion early during the course of therapy appear to be favorable signs. High perfusion suggests a high blood and oxygen supply to the tumor. The increase in tumor perfusion seen in some patients early during radiation therapy suggests improved oxygenation of previously hypoxic cells following early cell kill. Radiation therapy is more effective in eradicating these tumors, resulting in improved local control. Our technique may be helpful in identifying early-while more aggressive therapy can still be implemented-those patients who respond poorly to conventional radiation therapy.

The role of radiation therapy in the treatment of solitary plasmacytomas.

Between 1960 and 1985, 30 patients with solitary plasmacytomas were treated with radiotherapy at the University of Iowa: 13 patients with extramedullary plasmacytomas (EMP) and 17 with solitary plasmacytomas of bone (SPB). The local control rates were 92% for patients with EMP and 88% for those with SPB. Two of nine patients (22%) with EMP treated to the primary tumor only developed regional lymph node metastasis, indicating the need for elective irradiation of this area. The most common pattern of failure in both groups was progression to multiple myeloma. This occurred in 23% of the patients with EMP and 53% of those with SPB. The time course of progression to multiple myeloma differed for the two groups. All of those who progressed to multiple myeloma in the EMP group did so within 2 years, whereas a significant number of those in the SPB group progressed more than 5 years after initial therapy. None of five patients who received adjuvant chemotherapy in the SPB group progressed to multiple myeloma, compared to 75% (9/12) of the patients who did not receive chemotherapy.

Prophylactic T cell infusion after T cell-depleted bone marrow transplantation in patients with refractory lymphoma.

Fifty-two patients with refractory lymphoma were prospectively treated with prophylactic T lymphocyte infusion after T cell-depleted allogeneic bone marrow transplantation, to induce graft-versus-lymphoma effect. Thirty-three patients had related donors; 19 had unrelated donors. After transplantation with marrow that had 0.8 +/- 0.4 x 10(5)CD3(+) cells/kg, T cells up to 1.75 x 10(6) CD3(+) cells/kg were given over 3 months provided > or = grade II acute graft-versus-host disease (GVHD) was not seen. The cumulative incidence of grades II-IV acute GVHD was 69%. Twenty of 32 evaluable patients (63%) developed chronic GVHD. Ten patients (19%) died of GVHD. The Kaplan-Meier 5-year overall survival of all patients was 34%. On multivariate analyses, chronic GVHD was significant for relapse (hazard ratio of 1.7, P < 0.05), and for overall survival (hazard ratio 1.4, P < 0.001). Chemosensitivity was significant for relapse only on univariate analysis. Patients who developed chronic GVHD had 4 years median survival, compared with 9 months in patients without chronic GVHD, P < 0.001. The study shows that patients with chronic GVHD have superior survivals, most probably related to a graft-versus-lymphoma effect, which could be modulated by prophylactic T cell infusion.

Donor T-lymphocyte infusion for unrelated allogeneic bone marrow transplantation with CD3+ T-cell-depleted graft.

In T-cell-depleted allogeneic bone marrow transplantation (TCD-BMT) using unrelated donors, the role of donor lymphocyte infusion (DLI) for survival and disease control has not been defined. In a study of 116 patients (92 matched, 24 mismatched) who received CD3+ T-cell-depleted marrow graft, sequential infusions of escalated doses of donor T lymphocytes up to 1 x 10(6) CD3+ cells/kg were prospectively investigated. T cells were administered while patients were on cyclosporine, provided >or=grade II acute graft-versus-host-disease (GVHD) had not occurred. Acute GVHD of >or=grade II occurred in 27 of 110 (25%) patients before DLI and in 39 of 79 (49%) patients after DLI. In total, 12 of 27 (44%) patients without DLI and 44 of 72 (61%) patients who received DLI developed chronic GVHD. A total of 19 patients died of GVHD, with 17 of acute and two of chronic GVHD. Overall survival (OS) and event-free survival (EFS) at 5 years were 27 and 21%, respectively. The 2-year incidence of relapse was 14%. In multivariate analysis, only chronic GVHD was a good prognostic factor for both OS: hazard ratio (HR) 1.4, P=0.04, and EFS: HR 1.6, P=0.01. Both acute and chronic GVHD were favorable prognostic factors for relapse probability: HR 1.9 for both, P=0.02, 0.01, respectively. The 1-year cumulative incidence of transplant-related mortality (TRM), excluding cases of GVHD, was 42%. The two most common causes of 1-year non-GVHD death were viral infection (9%) and idiopathic pneumonia syndrome (12%). Although the incidence of relapse was low, the study suggests that the current scheme of DLI in unrelated TCD-BMT would not improve survival unless TRM decreases significantly.

Low rejection rate when using unrelated or haploidentical donors for children with leukemia undergoing marrow transplantation.

Thirty-nine children with leukemia were entered into a bone marrow transplantation study comparing the use of unrelated donors who were HLA-Dr identical and matched at least with three of the four HLA-A or B loci, with haploidentical related donors. Although marrows were prepared by T lymphocyte depletion in vitro, the rejection rate of marrow in these patients was only 13% (5/39). Four patients had early rejections, and three of these four had autologous recovery immediately without evidence of leukemic recurrence. The fifth had a delayed rejection occurring approximately 2 1/2 months after transplant. These results were achievable by an ablative regimen incorporating increased immunosuppression. Although the small sample size does not yet permit evaluation of outcome comparing one donor type versus another, the early findings document a high rate of successful engraftment.