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Autologous Bone Marrow Transplantation - Blog Science Connections

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516 Etoposide and Cisplatin for Lung Cancer<br />

carcinoma of the lung to determine the maximum dose of etoposide that could<br />

be administered safely in conjunction with high-dose cisplatin and autologous<br />

bone marrow reinfusion.<br />

MATERIALS AND METHODS<br />

Fifteen lung cancer patients representing 18 treatment courses were<br />

evaluated. Three patients had small cell carcinoma, two of whom had not<br />

achieved a complete remission with conventional combination chemoradiation<br />

therapy and one who had relapsed after attaining remission. Six patients had<br />

surgically unresectable non-small cell cancer previously untreated, and six had<br />

active non-small cell disease after therapy. The median age for all patients was<br />

59 years (range, 38-68 years). Twelve of these patients were men and three<br />

were women. No patient had evidence of active infection or tumorous<br />

involvement of the bone marrow. All patients had a Karnofsky performance<br />

status of at least 60%, an anticipated survival untreated greater than 8 weeks,<br />

measurable disease at physical examination or on external imaging, and no<br />

evidence of major organ system dysfunction not directly attributable to tumor.<br />

All patients had undergone a bone marrow harvest and cryopreservation<br />

procedure at least 4 weeks after completing any previous cytotoxic therapy. The<br />

marrow was frozen using previously described techniques and was stored in the<br />

liquid phase of a liquid nitrogen refrigerator until used (28). This protocol was<br />

approved by the Institutional Review Board for Human Subject Investigation of<br />

the University Hospitals of Cleveland, and all patients gave written informed<br />

consent.<br />

At the start of therapy, patient evaluation included a complete history,<br />

physical examination, tumor measurement studies, complete blood count,<br />

serum tests of liver and renal function, 24-hour urinalysis for creatinine<br />

clearance, and audiometry. Patients were treated in single hospital rooms<br />

without specialized isolation procedures. Central venous catheters, parenteral<br />

alimentation, broad-spectrum antibiotics, and irradiated (30 Qy) bloodcomponent<br />

support were used as indicated clinically. Persons with a history of<br />

"cold sores" or serum anti-herpes simplex antibody titers greater than 1:8<br />

received intravenous acyclovir for 14 days (day T-l through T+12). Time<br />

intervals were calculated from day 0, the day of marrow transplantation. The<br />

Eastern Cooperative Oncology Group (ECOG) criteria of response and toxicity<br />

were used to grade antitumor effect and organ system damage, respectively<br />

(except for hematologic dysfunction) (29). Frozen bone marrow was transported<br />

to the bedside in a liquid nitrogen-containing vessel for reinfusion 2 days<br />

after the final dose of chemotherapy. The marrow was thawed in a 37° C water<br />

bath and directly injected through a central venous catheter over 10 minutes<br />

without using blood filters.<br />

The treatment schema is shown in Table 1. Patients received intravenous<br />

hydration with 0.9% saline beginning 12 hours before the first dose of

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