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Factors associated with outcome following isolated meningeal relapse treated with craniospinal irradiation in childhood acute lymphoblastic leukemia
168
Radiation
Oncology,
Biology, Physics
Volume 21, Supplement
1
from completion of RT was 30.5 months (7-95 mos). A computerized dosimetric analysis based on dose-volume histogram was performed on 40 patients. RESULTS: Local control was achieved in 39 patients (95%), including 6 with aggressive fibromatosis. 29 patients (78%) had good or excellent functional outcomes. The mean score of all patients was 5.2 with a range of O-16. The rating system demonstrated minimal interobserver variability. There was an inverse relationship between volume irradiated to >55 Gy and functional score. Total dose was not a significant predictor. For patients wzth extremity tumors, mean score was 4.8 if tlOO0 cm3 received 55 Gy, in contrast to 7.2 if >lOOO cm3 was treated to this dose. A portion of the joint was treated in 29 patients and the entire joint in 25 (mean dose 48 Gy, range 45-65 Gy). Neither range of motion or total score was correlated with dose. Edema and functional score did not correlate with either the volume or percent of the limb receiving (40 Gy. The physician rated functional status compared well with the patients' self assessments. CONCLUSIONS: A system for functional assessment has been developed which is easily performed and provides detailed information about patient functional outcome. It can be used to evaluate the morbidity of combined modality sarcoma therapy. Doses up to 65 Gy, even over joint spaces, are not associated with significant morbidity. Only a small volume treated to ~40 Gy is required to maintain good outcome. The most important parameter appears to be the volume treated to >55 Gy. A detailed multivariate analysis of dosimetric parameters and surgical interventions versus functional parameters is underway.
101 AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR CHILDHOOD CALLA+ ACUTE LYMPHOBLASTIC LEUKEMIA EllenM. Kommehl, M.D.,1Amy Billett, M.D.,2 Stephen E. Sallan, M.D.,2 and Nancy J. Tarbell, M.D.1 IJoint Center for Radiation Therapy and 2Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Purpose: To study the efficacy of autologous bone marrow transplant (ABMT) for relapsed childhood CALLA+ acute lymphoblastic leukemia (ALL). Materials and Methods: Between 1978 and 1990.65 patients (pts) 5 18 years of age received ABMT for rela sed CALLA + ALL. Marrow ablation consisted of intensive combination chemotherapy with VM-26 200 mg/m2, ARA-C 3 gm/m ! and cyclophosphamide 1800 mg/m2 with total body irradiation (TBI). Pts received marrow pretreated in vitro with two anti-CALLA monoclonal antibodies. Prior to December 1985, 12 pts received 825-850 cGy single fraction TBI (SFTBI) and 15 pts received 1200-1300&y fractionated TBI (FfBI) at 5 cGy/min using a 4 MeV linear accelerator. Since 1985, ARA-C delivery has changed from continuous to bolus infusion and 1400 cGy TBI has been given in 8 fractions over 4 days using a double-headed 4 MeV linear accelerator facility at 10 cGy/min. Results: Twenty eight patients are relapse-free 6 months - 8.6 years post ABMT with a median follow-up of 27 months for survivors. Actuarial leukemia-free survival and overall survival are 46% f 8% and 40% + 7% at 3 years, respectively. There were thirteen treatment-related deaths (3 hemorrhage, 5 infectious complications, 2 interstitial pneumonitis, 1 sudden cardiac death, 1 veno-occlusive disease and 1 second tumor [AML]). Since introduction of 1400 cGy FTBI and bolus ARA-C, treatment-related deaths (3/33 vs. lo/30 pts transplanted before 1985) have declined (p=O.O4). Overall sites of relapse are 22 bone marrow, 2 CNS, 1 BM/testis, 1 BM/CNS, and 1 other. Of 18 pts at risk with prior CNS relapse, 2 isolated CNS and 1 simultaneous BM/CNS relapses were. observed. 2/2 isolated CNS relapses occurred in pts who had received no prior cranial irradiation whereas no patient given CNS irradiation (RT) following relapse (median dose=1275 cGy) subsequently recurred in the CNS post BMT. Of 9 pts at risk with previous testicular relapse, 1 pt. with no prior testicular RT experienced simultaneous testis/BM relapse and no patient who received prior testicular RT (median dose=2400 cGy) relapsed at a testicular site post BMT. Conclusion: This study demonstrates the efficacy of ABMT for relapsed childhood ALL. Treatment-related deaths have been reduced since modification of the ablative regimen. Since 1400 cGy FTBI was not adequate to prevent “sanctuary” recurrence in pts with pre-ABMT CNS or testicular relapse who had not received post-relapse RT, we have assumed a policy of boosting CNS or testicular sites in this group prior to ABMT when possible.
102 FACTORS ASSOCIATED WITH OUTCOME FOLLOWING ISOLATED MENINGEAL RELAPSE CRANIOSPINAL IRRADIATION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
TREATED
WITH
Parvesh Kumar, M.D., Larry E. Kun, M.D., H. Omar Hustu, M.D., Michael L. Hancock, MS., Gaston K. Rivera, M.D. St. Jude Children’s Research
Hospital, and the University of Tennessee
College of Medicine, Memphis, TN
Purpose: An analysis of factors associated with outcome following isolated meningeal relapse craniospinal irradiation (CSI) in childhood acute lymphoblastic leukemia (ALL) was conducted.
(MR) treated
with
Proceedings of the 33rd Annual ASTRO Meeting
169
Materials & Methods: Eighteen children with ALL entered on a prospective institutional trial totalling 344 patients between 1984 to 1988 developed an isolated MR during initial hematologic remission. MR occurred 3.5 - 42 mos. (median = 9 mos) post-diagnosis. Treatment included re-induction systemic therapy, intrathecal Methotrexate, Hydrocortisone and AraC (IT MHA) weekly until clearance of CSF cytology, followed by CSI. CSI delivered 24 Gy in 16 fractions to the cranium and 15 Gy in 10 fractions to the spine. Systemic chemotherapy was continued for a minimum of one year post-MR. Results: Clearance of CSF cytology was documented in all patients after l-5 IT MHA’s (median = 2). At a follow-up of lo-48 mos. post-MR (median = 30 mos.), lo/18 children are in secondary complete remission. The 4-year post-MR Kaplan Meier survival and event-free survival (EFS) are 57% and 51%, respectively. Bone marrow relapse has occurred in 4 cases. Second MR has been documented in 4 children: 3 as isolated events and one combined with bone marrow/testicular failure. Comparison of disease factors between the four patients with second MR and the other 14 cases with sustained CNS remission indicate the following: (1) high white blood cell count at diagnosis (median, 459,000 vs. 93,100, respectively, p = O.Ol), (2) preponderance of T-cell immunophenotype (4/4 vs. 4/13, respectively, p = 0.03) and (3) suggestive correlation between interval to first MR and interval to second event (p = 0.09, r = 0.64). DNA index (51.16 or >1.16), presence of chromosomal translocations, and CNS involvement at initial diagnosis did not appear to predict a higher probability of second MR. The presence of Philadelphia chromosome (3/4 vs. O/13, p = 0.01) appeared to be the most significant factor associated with outcome in the four patient:, experiencing a bone marrow relapse. Conclusion: Prolonged EFS can be achieved in approximately 50% of the children with isolated MR in childhood ALL treated with added chemotherapy and CSI. Further consideration should be given to more aggressive therapy following isolated MR in those patients with hyperleukocytosis at diagnosis and T-cell immunophenotype as these factors appear to predict a higher likelihood of subsequent CNS failure.
103 RADIATION
THERAPY
Kern J. Minehanl,
FOR DIABETES
Michae’ G. Chenl,
INSIPIDUS
CAUSED
Donald Zimmerman?
BY LANGERHANS
John Q.
Mayo Clinic, Rochester MN 55905, 1 Division of Radiation Section of Biostatistics, 4 Section of Surgical Pathology
Su3,
Oncology,
CELL HISTIOCYTOSIS
Thomas V. Colbya, Edward G. Shawl 2 Section
of Pediatric
Endocrinology,
3
Diabetes insipidus (DI) is relatively common in patients (pts) with Langerhans cell histiocytosis Purpose: (LCH). Hypothalamic-pituitary radiation therapy (HPRT) has been the standard treatment. This study assesses the efficacy of HPRT in LCH-associated DI. Between 1950 and 1986, 45 patients with pathologically confirmed LCH developed Materials & Methods: DI. All received pitressin therapy. The pts were divided into two groups on the basis of additional treatment for the DI. Twenty-eight pts (the radiation group) received pitressin and HPRT (20 with concomitant chemotherapy). Seventeen pts (the control group) did not receive HPRT (11 received pitressin and chemotherapy while 6 received pitressin alone). The mean and range of radiation doses were 10.8 gray (Gy) and 2.14-30 Gy respectively. Most patients (88%) were less than 20 years old at diagnosis. The two treatment groups were s,imilar in patient characteristics (age, sex, lung involvement, head and neck bone involvement) except age and lung involvement, both of which were significantly less in the radiation group. Treatment response was defined as follows: Partial response (PR)- A reduction in pitressin dosage and/or improvement in computed tomography (CT) or Magnetic Resonance Image (MRI) radiographs; Complete response(CR)- No further need for pitressin therapy and/or normalization of CT/MRI. Endpoints analyzed included treatment response, pts characteristics, and survival. Results: In the radiation group, 36% (10/28) obtained a response to HPRT (22% CR and 14% PR) whereas Five of the 6 complete responders were radiated within 14 days of the none in the control group responded. diagnosis of DI. The mean dose utilized in the responding and nonresponding pts was 11.2, and IO Gy respectively. Three of 5 (60%) pts treated with more than 15 Gy responded compared to 7 of 23 (30%) treated with < 15 Gy. Eight of the IO responders compared to 16 of 35 nonresponders were female. Only 1 in 20 pts with concomitant lung histiocytosis responded. Actuarial survivals at 5, 10, 20, 40 years for the entire group were 80, 7j3, 75, & 65% with a median follow-up in living patients of 14.7 years. Conclusions: Thirty-six percent of patients with LCH-induced DI respond to low-dose HPRT. Doses > 15 Gy may result in improved response rate. Radiation should be delivered as soon as possible after the diagnosis of DI.
Radiation
Oncology,
Biology, Physics
Volume 21, Supplement
1
from completion of RT was 30.5 months (7-95 mos). A computerized dosimetric analysis based on dose-volume histogram was performed on 40 patients. RESULTS: Local control was achieved in 39 patients (95%), including 6 with aggressive fibromatosis. 29 patients (78%) had good or excellent functional outcomes. The mean score of all patients was 5.2 with a range of O-16. The rating system demonstrated minimal interobserver variability. There was an inverse relationship between volume irradiated to >55 Gy and functional score. Total dose was not a significant predictor. For patients wzth extremity tumors, mean score was 4.8 if tlOO0 cm3 received 55 Gy, in contrast to 7.2 if >lOOO cm3 was treated to this dose. A portion of the joint was treated in 29 patients and the entire joint in 25 (mean dose 48 Gy, range 45-65 Gy). Neither range of motion or total score was correlated with dose. Edema and functional score did not correlate with either the volume or percent of the limb receiving (40 Gy. The physician rated functional status compared well with the patients' self assessments. CONCLUSIONS: A system for functional assessment has been developed which is easily performed and provides detailed information about patient functional outcome. It can be used to evaluate the morbidity of combined modality sarcoma therapy. Doses up to 65 Gy, even over joint spaces, are not associated with significant morbidity. Only a small volume treated to ~40 Gy is required to maintain good outcome. The most important parameter appears to be the volume treated to >55 Gy. A detailed multivariate analysis of dosimetric parameters and surgical interventions versus functional parameters is underway.
101 AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR CHILDHOOD CALLA+ ACUTE LYMPHOBLASTIC LEUKEMIA EllenM. Kommehl, M.D.,1Amy Billett, M.D.,2 Stephen E. Sallan, M.D.,2 and Nancy J. Tarbell, M.D.1 IJoint Center for Radiation Therapy and 2Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Purpose: To study the efficacy of autologous bone marrow transplant (ABMT) for relapsed childhood CALLA+ acute lymphoblastic leukemia (ALL). Materials and Methods: Between 1978 and 1990.65 patients (pts) 5 18 years of age received ABMT for rela sed CALLA + ALL. Marrow ablation consisted of intensive combination chemotherapy with VM-26 200 mg/m2, ARA-C 3 gm/m ! and cyclophosphamide 1800 mg/m2 with total body irradiation (TBI). Pts received marrow pretreated in vitro with two anti-CALLA monoclonal antibodies. Prior to December 1985, 12 pts received 825-850 cGy single fraction TBI (SFTBI) and 15 pts received 1200-1300&y fractionated TBI (FfBI) at 5 cGy/min using a 4 MeV linear accelerator. Since 1985, ARA-C delivery has changed from continuous to bolus infusion and 1400 cGy TBI has been given in 8 fractions over 4 days using a double-headed 4 MeV linear accelerator facility at 10 cGy/min. Results: Twenty eight patients are relapse-free 6 months - 8.6 years post ABMT with a median follow-up of 27 months for survivors. Actuarial leukemia-free survival and overall survival are 46% f 8% and 40% + 7% at 3 years, respectively. There were thirteen treatment-related deaths (3 hemorrhage, 5 infectious complications, 2 interstitial pneumonitis, 1 sudden cardiac death, 1 veno-occlusive disease and 1 second tumor [AML]). Since introduction of 1400 cGy FTBI and bolus ARA-C, treatment-related deaths (3/33 vs. lo/30 pts transplanted before 1985) have declined (p=O.O4). Overall sites of relapse are 22 bone marrow, 2 CNS, 1 BM/testis, 1 BM/CNS, and 1 other. Of 18 pts at risk with prior CNS relapse, 2 isolated CNS and 1 simultaneous BM/CNS relapses were. observed. 2/2 isolated CNS relapses occurred in pts who had received no prior cranial irradiation whereas no patient given CNS irradiation (RT) following relapse (median dose=1275 cGy) subsequently recurred in the CNS post BMT. Of 9 pts at risk with previous testicular relapse, 1 pt. with no prior testicular RT experienced simultaneous testis/BM relapse and no patient who received prior testicular RT (median dose=2400 cGy) relapsed at a testicular site post BMT. Conclusion: This study demonstrates the efficacy of ABMT for relapsed childhood ALL. Treatment-related deaths have been reduced since modification of the ablative regimen. Since 1400 cGy FTBI was not adequate to prevent “sanctuary” recurrence in pts with pre-ABMT CNS or testicular relapse who had not received post-relapse RT, we have assumed a policy of boosting CNS or testicular sites in this group prior to ABMT when possible.
102 FACTORS ASSOCIATED WITH OUTCOME FOLLOWING ISOLATED MENINGEAL RELAPSE CRANIOSPINAL IRRADIATION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
TREATED
WITH
Parvesh Kumar, M.D., Larry E. Kun, M.D., H. Omar Hustu, M.D., Michael L. Hancock, MS., Gaston K. Rivera, M.D. St. Jude Children’s Research
Hospital, and the University of Tennessee
College of Medicine, Memphis, TN
Purpose: An analysis of factors associated with outcome following isolated meningeal relapse craniospinal irradiation (CSI) in childhood acute lymphoblastic leukemia (ALL) was conducted.
(MR) treated
with
Proceedings of the 33rd Annual ASTRO Meeting
169
Materials & Methods: Eighteen children with ALL entered on a prospective institutional trial totalling 344 patients between 1984 to 1988 developed an isolated MR during initial hematologic remission. MR occurred 3.5 - 42 mos. (median = 9 mos) post-diagnosis. Treatment included re-induction systemic therapy, intrathecal Methotrexate, Hydrocortisone and AraC (IT MHA) weekly until clearance of CSF cytology, followed by CSI. CSI delivered 24 Gy in 16 fractions to the cranium and 15 Gy in 10 fractions to the spine. Systemic chemotherapy was continued for a minimum of one year post-MR. Results: Clearance of CSF cytology was documented in all patients after l-5 IT MHA’s (median = 2). At a follow-up of lo-48 mos. post-MR (median = 30 mos.), lo/18 children are in secondary complete remission. The 4-year post-MR Kaplan Meier survival and event-free survival (EFS) are 57% and 51%, respectively. Bone marrow relapse has occurred in 4 cases. Second MR has been documented in 4 children: 3 as isolated events and one combined with bone marrow/testicular failure. Comparison of disease factors between the four patients with second MR and the other 14 cases with sustained CNS remission indicate the following: (1) high white blood cell count at diagnosis (median, 459,000 vs. 93,100, respectively, p = O.Ol), (2) preponderance of T-cell immunophenotype (4/4 vs. 4/13, respectively, p = 0.03) and (3) suggestive correlation between interval to first MR and interval to second event (p = 0.09, r = 0.64). DNA index (51.16 or >1.16), presence of chromosomal translocations, and CNS involvement at initial diagnosis did not appear to predict a higher probability of second MR. The presence of Philadelphia chromosome (3/4 vs. O/13, p = 0.01) appeared to be the most significant factor associated with outcome in the four patient:, experiencing a bone marrow relapse. Conclusion: Prolonged EFS can be achieved in approximately 50% of the children with isolated MR in childhood ALL treated with added chemotherapy and CSI. Further consideration should be given to more aggressive therapy following isolated MR in those patients with hyperleukocytosis at diagnosis and T-cell immunophenotype as these factors appear to predict a higher likelihood of subsequent CNS failure.
103 RADIATION
THERAPY
Kern J. Minehanl,
FOR DIABETES
Michae’ G. Chenl,
INSIPIDUS
CAUSED
Donald Zimmerman?
BY LANGERHANS
John Q.
Mayo Clinic, Rochester MN 55905, 1 Division of Radiation Section of Biostatistics, 4 Section of Surgical Pathology
Su3,
Oncology,
CELL HISTIOCYTOSIS
Thomas V. Colbya, Edward G. Shawl 2 Section
of Pediatric
Endocrinology,
3
Diabetes insipidus (DI) is relatively common in patients (pts) with Langerhans cell histiocytosis Purpose: (LCH). Hypothalamic-pituitary radiation therapy (HPRT) has been the standard treatment. This study assesses the efficacy of HPRT in LCH-associated DI. Between 1950 and 1986, 45 patients with pathologically confirmed LCH developed Materials & Methods: DI. All received pitressin therapy. The pts were divided into two groups on the basis of additional treatment for the DI. Twenty-eight pts (the radiation group) received pitressin and HPRT (20 with concomitant chemotherapy). Seventeen pts (the control group) did not receive HPRT (11 received pitressin and chemotherapy while 6 received pitressin alone). The mean and range of radiation doses were 10.8 gray (Gy) and 2.14-30 Gy respectively. Most patients (88%) were less than 20 years old at diagnosis. The two treatment groups were s,imilar in patient characteristics (age, sex, lung involvement, head and neck bone involvement) except age and lung involvement, both of which were significantly less in the radiation group. Treatment response was defined as follows: Partial response (PR)- A reduction in pitressin dosage and/or improvement in computed tomography (CT) or Magnetic Resonance Image (MRI) radiographs; Complete response(CR)- No further need for pitressin therapy and/or normalization of CT/MRI. Endpoints analyzed included treatment response, pts characteristics, and survival. Results: In the radiation group, 36% (10/28) obtained a response to HPRT (22% CR and 14% PR) whereas Five of the 6 complete responders were radiated within 14 days of the none in the control group responded. diagnosis of DI. The mean dose utilized in the responding and nonresponding pts was 11.2, and IO Gy respectively. Three of 5 (60%) pts treated with more than 15 Gy responded compared to 7 of 23 (30%) treated with < 15 Gy. Eight of the IO responders compared to 16 of 35 nonresponders were female. Only 1 in 20 pts with concomitant lung histiocytosis responded. Actuarial survivals at 5, 10, 20, 40 years for the entire group were 80, 7j3, 75, & 65% with a median follow-up in living patients of 14.7 years. Conclusions: Thirty-six percent of patients with LCH-induced DI respond to low-dose HPRT. Doses > 15 Gy may result in improved response rate. Radiation should be delivered as soon as possible after the diagnosis of DI.