1
recurrence in previously uninvolved areas not included in the initial target volume. Three were re-irradiated with anterior fields to the whole orbit and one underwent resection alone. All of these patients are free of disease at the latest follow up. One out of ten (10%) patients treated with whole orbit irradiation developed a recurrence in the skin and soft tissues lateral to the orbit. She is disease free after further radiotherapy to these sites. Conclusions: In our small retrospective study patients with orbital lymphoma treated with radiotherapy to partial orbit volumes suffered from an unacceptable 33% incidence of intra-orbital recurrence outside of the PTV. This may be explained by the existence of subclininal disease in seemingly unaffected intra-orbital areas. Reducing the PTV to exclude uninvolved intra-orbital areas did not result in less toxicity than whole orbit irradiation. Doses of irradiation of the order of 25 Gy are effective to treat most low-grade orbital lymphomas. These doses result in minimal morbidity even when delivered to the entire orbit. Patients with orbital lymphoma should therefore be treated with low dose radiation to the entire orbit. 1051 Low Dose Total Body Irradiation (TBI) In Outpatient Non-Myeloablative Bone Marrow Transplantation R.M. Macklis, 1 M. Kalaycio, 2 R. Sobecks, 2 B. Pohlman, 2 S. Brown, 2 B. Bolwell 2 1 Radiation Oncology, Cleveland Clinic, Cleveland, OH, 2 Medical Oncology, Cleveland Clinic, Cleveland, OH Purpose/Objective: Myeloablative Bone Marrow Transplantation (BMT) using either TBI or dose-intense chemotherapy has now become standard management for refractory hematopoietic tumors. However, standard preparative regimens often result in unacceptably high risks of pulmonary, hepatic, and renal toxicity. For allogeneic BMT, these risks are compounded by the risk of graft rejection or graft v. host disease (GVHD). Increased immunosuppression used to prevent GVHD has unfortunately resulted in higher rates of disease recurrence, leading many investigators to conclude that a large part of the therapeutic benefit of BMT resides in the immunologic response engendered by a minor degree of GVHD (the graft v. tumor effect, GVT). This realization has lead to a radical new approach to BMT in which the intensity of the prep regimen is deliberately decreased below the level required for marrow ablation. The chimerism produced by non-myeloablative BMT (NMBMT) is modulated to optimize GVT while still minimizing organ toxicity. Low dose TBI (2Gy) in conjunction with moderate dose fludarabine (FLU) represents one promising regimen for NMBMT. The NMBMT cohort has now become the largest group of TBI-prepared transplant patients at our institution. Materials/Methods: Forty-one patients have undergone NMBMT since 2000. Indications for NMBMT have included NHL, myelodysplastic syndromes, Waldenstroms, AML, CML, myeloma, CLL, and renal cell ca. 35 of these patients are evaluable with at least three months of follow-up. Twenty-seven patients received sibling stem cells, whereas 8 patients received matched unrelated donor (MUD) stem cells or marrow through the national marrow transplant registry. All patients received TBI (2 Gy) delivered using a 6 MV linear accelerator, dose rate 10 –20 cGy per minute with beam spoiler and TLD dosimetry. The FLU was delivered in the 3 days prior to TBI, and the donor stem cells were infused the following day. The NMBMT was carried out entirely in the outpatient environment except for complications. Results: Despite the fact that 8 patients had previously undergone a failed autotransplant using either high dose Busulfan/ Cytoxan or TBI, no patient suffered profound pulmonary, renal, or hepatic toxicity. The majority of these re-transplant patients did show some low level of serious but non-life threatening organ toxicity, with 6/8 showing a modest decrease in FEV1 levels (2–21%). For the 27 patients transplanted using well matched sibling stem cells, all patients engrafted with an average day 21 ANC of 7.17 and platelet count of 145 K. Seven patients remain in CR with a median follow up time of 2 years. One patient is currently alive with disease and 11 patients have expired (6 from GVHD and 5 from progression). For the 8 patients undergoing NMBMT using MUD transplants, no patients are currently alive in CR. Four of these patients experienced primary graft failure and 3 expired of GVHD. Conclusions: (1) NMBMT utilizing low dose TBI and FLU represents an important new approach to allogeneic BMT, with substantially lower toxicities than fully ablative transplantation. The ability to conduct this sort of transplant program in an outpatient environment greatly expands the flexibility and dramatically decreases the costs of the program. (2) Radiation-related organ toxicity appears manageable, even in patients who have previously undergone a failed high-dose BMT. (3) When sibling marrow is available, the NMBMT approach yields intermediate-term DFS rates on the order of 33%. However, control rates using MUD donors currently appear unsatisfactory. Our next generation of NMBMT protocols will explore somewhat more intensive preparative regimens incorporating either higher doses of TBI (perhaps 4 Gy) or targeted radiation boosts delivered via external beam irradiation or anti-CD20 radio-immunotherapy. (4) Diseases that have shown especially promising early results with the current regimen include NHL and CML. Diseases in which our current preparative regimen appears unsatisfactory include renal cell carcinoma, multiple myeloma, and AML. 1052 C225 Anti-EGFR (Epidermal Growth Factor Receptor) Antibody Enhances the Efficacy of Docetaxel Chemoradiotherapy E. Nakata, 3,1 U. Raju, 1 N. Hunter, 1 K. Mason, 1 Z. Fan, 4 K.K. Ang, 2 S. Yamada, 3 L. Milas 1 1 Experimental Radiation Oncology - 066, UT MD Anderson Cancer Center, Houston, TX, 2 Division of Radiation Oncology - 097, UT MD Anderson Cancer Center, Houston, TX, 3 Radiation Oncology, Tohoku University Medical School, Sendai, Japan, 4 Experimental Therapeutics, UT MD Anderson Cancer Center, Houston, TX Purpose/Objective: Our earlier studies showed that C225 anti-EGFR antibody enhances tumor radioresponse (Clin Cancer Res 200;6:701–708), and studies by others demonstrated that this antibody improves the antitumor efficacy of a number of chemotherapeutic agents. Because of increased use of chemoradiotherapy in cancer treatment, it is important to determine whether C225 also enhances chemoradiotherapy. This study assessed the effect of C225 on tumor response when combined with docetaxel plus single or fractionated radiation. Materials/Methods: MDA468 human adenocarcinoma cells growing as xenografts in the right hind leg of nude mice were used. Mice bearing 8 mm tumors were treated with C225 antibody at a dose of 1 mg given ip once or twice 3 days apart, 10 mg/kg docetaxel given iv, and/or local tumor irradiation of 8 Gy single dose or fractionated irradiation consisting of 2 Gy daily for 5 days. When all 3 agents were combined, C225 was given 6 h before docetaxel and radiation was given 24 h after docetaxel. The treatment endpoint was tumor growth delay. S292 I. J. Radiation Oncology Biology Physics Volume 57, Number 2, Supplement, 2003

Low dose total body irradiation (TBI) in outpatient non-myeloablative bone marrow transplantation

Embed Size (px)

Citation preview

Page 1: Low dose total body irradiation (TBI) in outpatient non-myeloablative bone marrow transplantation

recurrence in previously uninvolved areas not included in the initial target volume. Three were re-irradiated with anterior fieldsto the whole orbit and one underwent resection alone. All of these patients are free of disease at the latest follow up. One outof ten (10%) patients treated with whole orbit irradiation developed a recurrence in the skin and soft tissues lateral to the orbit.She is disease free after further radiotherapy to these sites.

Conclusions: In our small retrospective study patients with orbital lymphoma treated with radiotherapy to partial orbit volumessuffered from an unacceptable 33% incidence of intra-orbital recurrence outside of the PTV. This may be explained by theexistence of subclininal disease in seemingly unaffected intra-orbital areas. Reducing the PTV to exclude uninvolvedintra-orbital areas did not result in less toxicity than whole orbit irradiation. Doses of irradiation of the order of 25 Gy areeffective to treat most low-grade orbital lymphomas. These doses result in minimal morbidity even when delivered to the entireorbit. Patients with orbital lymphoma should therefore be treated with low dose radiation to the entire orbit.

1051 Low Dose Total Body Irradiation (TBI) In Outpatient Non-Myeloablative Bone Marrow Transplantation

R.M. Macklis,1 M. Kalaycio,2 R. Sobecks,2 B. Pohlman,2 S. Brown,2 B. Bolwell2

1Radiation Oncology, Cleveland Clinic, Cleveland, OH, 2Medical Oncology, Cleveland Clinic, Cleveland, OH

Purpose/Objective: Myeloablative Bone Marrow Transplantation (BMT) using either TBI or dose-intense chemotherapy hasnow become standard management for refractory hematopoietic tumors. However, standard preparative regimens often resultin unacceptably high risks of pulmonary, hepatic, and renal toxicity. For allogeneic BMT, these risks are compounded by therisk of graft rejection or graft v. host disease (GVHD). Increased immunosuppression used to prevent GVHD has unfortunatelyresulted in higher rates of disease recurrence, leading many investigators to conclude that a large part of the therapeutic benefitof BMT resides in the immunologic response engendered by a minor degree of GVHD (the graft v. tumor effect, GVT). Thisrealization has lead to a radical new approach to BMT in which the intensity of the prep regimen is deliberately decreased belowthe level required for marrow ablation. The chimerism produced by non-myeloablative BMT (NMBMT) is modulated tooptimize GVT while still minimizing organ toxicity. Low dose TBI (2Gy) in conjunction with moderate dose fludarabine (FLU)represents one promising regimen for NMBMT. The NMBMT cohort has now become the largest group of TBI-preparedtransplant patients at our institution.

Materials/Methods: Forty-one patients have undergone NMBMT since 2000. Indications for NMBMT have included NHL,myelodysplastic syndromes, Waldenstroms, AML, CML, myeloma, CLL, and renal cell ca. 35 of these patients are evaluablewith at least three months of follow-up. Twenty-seven patients received sibling stem cells, whereas 8 patients received matchedunrelated donor (MUD) stem cells or marrow through the national marrow transplant registry. All patients received TBI (2 Gy)delivered using a 6 MV linear accelerator, dose rate 10–20 cGy per minute with beam spoiler and TLD dosimetry. The FLUwas delivered in the 3 days prior to TBI, and the donor stem cells were infused the following day. The NMBMT was carriedout entirely in the outpatient environment except for complications.

Results: Despite the fact that 8 patients had previously undergone a failed autotransplant using either high dose Busulfan/Cytoxan or TBI, no patient suffered profound pulmonary, renal, or hepatic toxicity. The majority of these re-transplant patientsdid show some low level of serious but non-life threatening organ toxicity, with 6/8 showing a modest decrease in FEV1 levels(2–21%). For the 27 patients transplanted using well matched sibling stem cells, all patients engrafted with an average day 21ANC of 7.17 and platelet count of 145 K. Seven patients remain in CR with a median follow up time of �2 years. One patientis currently alive with disease and 11 patients have expired (6 from GVHD and 5 from progression). For the 8 patientsundergoing NMBMT using MUD transplants, no patients are currently alive in CR. Four of these patients experienced primarygraft failure and 3 expired of GVHD.

Conclusions: (1) NMBMT utilizing low dose TBI and FLU represents an important new approach to allogeneic BMT, withsubstantially lower toxicities than fully ablative transplantation. The ability to conduct this sort of transplant program in anoutpatient environment greatly expands the flexibility and dramatically decreases the costs of the program. (2) Radiation-relatedorgan toxicity appears manageable, even in patients who have previously undergone a failed high-dose BMT. (3) When siblingmarrow is available, the NMBMT approach yields intermediate-term DFS rates on the order of 33%. However, control ratesusing MUD donors currently appear unsatisfactory. Our next generation of NMBMT protocols will explore somewhat moreintensive preparative regimens incorporating either higher doses of TBI (perhaps 4 Gy) or targeted radiation boosts deliveredvia external beam irradiation or anti-CD20 radio-immunotherapy. (4) Diseases that have shown especially promising earlyresults with the current regimen include NHL and CML. Diseases in which our current preparative regimen appearsunsatisfactory include renal cell carcinoma, multiple myeloma, and AML.

1052 C225 Anti-EGFR (Epidermal Growth Factor Receptor) Antibody Enhances the Efficacy of DocetaxelChemoradiotherapy

E. Nakata,3,1 U. Raju,1 N. Hunter,1 K. Mason,1 Z. Fan,4 K.K. Ang,2 S. Yamada,3 L. Milas1

1Experimental Radiation Oncology - 066, UT MD Anderson Cancer Center, Houston, TX, 2Division of Radiation Oncology- 097, UT MD Anderson Cancer Center, Houston, TX, 3Radiation Oncology, Tohoku University Medical School, Sendai,Japan, 4Experimental Therapeutics, UT MD Anderson Cancer Center, Houston, TX

Purpose/Objective: Our earlier studies showed that C225 anti-EGFR antibody enhances tumor radioresponse (Clin Cancer Res200;6:701–708), and studies by others demonstrated that this antibody improves the antitumor efficacy of a number ofchemotherapeutic agents. Because of increased use of chemoradiotherapy in cancer treatment, it is important to determinewhether C225 also enhances chemoradiotherapy. This study assessed the effect of C225 on tumor response when combined withdocetaxel plus single or fractionated radiation.

Materials/Methods: MDA468 human adenocarcinoma cells growing as xenografts in the right hind leg of nude mice wereused. Mice bearing 8 mm tumors were treated with C225 antibody at a dose of 1 mg given ip once or twice 3 days apart, 10mg/kg docetaxel given iv, and/or local tumor irradiation of 8 Gy single dose or fractionated irradiation consisting of 2 Gy dailyfor 5 days. When all 3 agents were combined, C225 was given 6 h before docetaxel and radiation was given 24 h after docetaxel.The treatment endpoint was tumor growth delay.

S292 I. J. Radiation Oncology ● Biology ● Physics Volume 57, Number 2, Supplement, 2003