Lawrence D. Durack

Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue.

PURPOSE Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND METHODS Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty-nine patients received therapeutic infusions of single-agent (131)I-anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi [10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support. RESULTS Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic dose-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS). CONCLUSION Myeloablative (131)I-anti-B1 RIT is relatively well tolerated when given with autologous stem-cell support and often results in prolonged remission durations with few late toxicities.

Considerations for imaging Re-188 and Re-186 isotopes

Re-186 and Re-188 have been suggested for radioimmunotherapy because of their energetic beta particles, imageable gamma photons, and chemical properties similar to technetium. Because of this potential, these isotopes were evaluated before in vivo imaging was attempted. It was found that low-abundance, high-energy gamma photons present in these rhenium isotopes require a medium-energy collimator to yield optimal image resolution and count rate, which are critical factors in the performance of preliminary imaging studies on patients for antibody imaging and therapy.

Post therapy imaging in high dose I‐131 radioimmunotherapy patients

The biodistribution of a trace-labeled I-131 antibody is used to predict the biodistribution of a high dose I-131 antibody for therapy. Internal radiation dose estimates derived from the trace-labeled antibody have been used to determine the I-131 doses in a phase I escalating dose therapy trial for hematologic malignancy. To confirm the hypothesis that the distribution of a trace- and high-dose labeled antibodies are similar, both trace (7-11 mCi, 259-407 MBq) and high-dose (100-800 mCi, 3700-29600 MBq) I-131 radiolabeled antibody infusion were imaged in 12 patients who were treated for leukemia or lymphoma. With specialized imaging techniques using lead attenuation sheets, clearance data from organs were obtained from serial gamma camera images. Biological clearance half times of I-131 from both trace and therapy level doses were in agreement. An exception was a patient who developed human antimouse antibody before therapy, and subsequently had rapid clearance of the therapy dose. The method was feasible, yielded reproducible results, and provided critical data for relating therapy toxicity to radiation absorbed dose estimates.

Recombinant human macrophage colony‐stimulating factor‐induced thrombocytopenia in dogs

Summary. To characterize recombinant human macrophage‐colony stimulating factor (rhM‐CSF)‐associated thrombocytopenia (TCP), in vivo studies were performed in dogs, including the biodistributions and recoveries of radiolabelled autologous and allogeneic platelets. rhM‐CSF induced a reversible, dose‐dependent decrease in platelet counts. The number of megakaryocytes in spleen and marrow of rhM‐CSF‐treated dogs was increased two to threefold. Recoveries of allogeneic platelets transfused from rhM‐CSF‐treated donors into tolerized recipients (n = 3) were not significantly different from allogeneic baseline studies (93 ± 10% of baseline values at 24 h and 90 ± 1% at 40 h), whereas autologous platelets infused back into rhM‐CSF‐treated donors had decreased recoveries (45 ± 2% of baseline values at 24 h, P = 0·03 and 20 ± 4% at 40 h, P = 0·001). Platelet biodistribution studies showed increased accumulation of radiolabelled platelets over the spleens and livers of rhM‐CSF‐treated dogs. Histochemistry showed increased levels of platelet‐specific antigen (CD41; glycoprotein IIb) associated with Kupffer cells. The sensitivity of platelets from rhM‐CSF‐treated dogs to activation from thrombin, as measured by expression of P‐selectin (CD62P), was not significantly different when compared with baseline studies (P = 0·18; n = 4). These results support the concept that rhM‐CSF induces an activation of the monocyte–macrophage system (MMS), which causes a reversible TCP in a dog model.