Samuel A. Jacobs

Use of Plasma Pharmacokinetics to Predict and Prevent Methotrexate Toxicity

To correlate the pharmacokinetics and toxicity of methotrexate, we measured the drugs clearance from plasma after 395 high-dose, six-hour infusions given to 78 patients. After 375 infusions, 48 hour methotrexate levels fell within 2 standard deviations of the mean for nontoxic infusions, and myelosuppression did not occur. Methotrexate concentrations exceeded the range for nontoxic patients (mean +/- 2 standard deviations) after 20 infusions. Serious myelosuppression occurred after six of these 20 infusions, including five of 12 infusions associated with 48-hour drug concentrations above 9 X 10(-7) M. In seven patients with 48-hour concentrations above 9 X 10(-7) M, the absence of toxicity could be attributed to subsequent rapid clearance of the drug; four of these patients also received large doses of supplemental leucovorin (50 to 100 mg per square meter every six hours). Determination of methotrexate concentration in plasma thus identified patients at high risk of toxicity, a group that may benefit from supplemental leucovorin rescue.

Phase II Trial of Short-Course CHOP-R Followed by 90Y-ibritumomab Tiuxetan and Extended Rituximab in Previously Untreated Follicular Lymphoma

Purpose: Radioimmunotherapy has been approved for relapsed follicular lymphoma (FL), including rituximab-refractory FL. This study was designed to determine the CR rate with short-course chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R) followed by 90-Y ibritumomab tiuxetan (RIT) with extended rituximab as first-line treatment. Experimental Design: Between March 2004 and February 2007, 60 patients with stage II to IV symptomatic or bulky FL from a single institution supported by a large community network entered this phase II trial. Patients received CHOP-R for three treatment cycles before RIT followed by four additional weekly treatments with rituximab. Response was determined using fusion [18 F] fluorodeoxyglucose-positron emission tomography (PET)-computed tomography (CT) imaging. Results: Of the 60 patients entering this trial, 55 patients completed all protocol therapy. The median follow up was 19.7 months (range, 0.26-35.9 months). For intent-to-treat analysis, the complete response (CR) rate after CHOP-R, as assessed by CT and PET imaging, was 40% and 46%, respectively. After RIT, the CR rate improved, as assessed by CT and PET imaging, to 82% and 89%, respectively. Ten patients have progressed, including eight from best response of CR. Seven of 18 patients who were PET positive after CHOP-R progressed compared with 3 of 37 patients who were PET negative (P = 0.010). Conclusions: In patients with previously untreated, symptomatic or bulky FL, short-course chemoimmunotherapy and consolidation RIT and extended rituximab resulted in a high CR rate. Failure to achieve an early PET CR after CHOP-R indicated high risk of relapse.

Methotrexate Disposition in Humans: Case Studies in Ovarian Cancer and Following High-Dose Infusion

(1978). Methotrexate Disposition in Humans: Case Studies in Ovarian Cancer and Following High-Dose Infusion. Drug Metabolism Reviews: Vol. 8, No. 1, pp. 107-117.

Candida arthritis treated with amphotericin B

This report describes a patient with acute lymphoblastic leukemia who developed arthritis of the knee caused by Candida tropicalis. Systemic therapy with amphotericin B apparently suppressed but did not eliminate the infection. Resolution of the arthritis occurred only after three intra-articular injections of amphotericin B. Intra-articular administration of amphotericin B may be a useful adjunct to systemic antifungal therapy in the treatment of these infections.

Serum sickness in a patient with follicular lymphoma after rituximab and radioimmunotherapy with ibritumomab tiuxetan.

A previously healthy 47-year-old woman was treated for follicular lymphoma, grade III, with cyclophosphamide, adriamycin, vincristine, prednisone with rituximab (CHOP-R) followed by ibritumomab tiuxetan and rituximab. She developed a serum sickness-like illness during immunotherapy with fever, myalgias, arthralgias, and pleural and pericardial effusions. Despite anti-inflammatory therapies her symptoms persisted for 10 months before ultimate resolution. Her clinical course and literature are reviewed.

Anaphylaxis after administration of ibritumomab tiuxetan for follicular non-hodgkin lymphoma.

We report an anaphylactic reaction in a 45-year-old gentleman with an 8-year history of extensively treated, relapsing follicular lymphoma who was receiving a second treatment with ibritumomab tiuxetan. Within seconds of receiving Y-90 ibritumomab, he developed chest tightness, shallow respirations, hypotension, and incontinence. After successful resuscitation, a human antimouse antibody (HAMA) level was found to be elevated, 618 ng/mL (reference 0–188 ng/mL).

A Putative Case of Methotrexate-Related Lymphoma: Clinical Course and PET/CT Findings

Patients with autoimmune conditions develop lymphoproliferative disorders (LPDs) at a higher frequency than normal both in association with and independent of Methotrexate (MTX). We describe a case of MTX-associated lymphoma in a patient with psoriasis on long-standing MTX. The case is notable for the initial tumor burden, the dramatic disappearance of the PET-CT findings on discontinuation of MTX, and the subsequent early regrowth of disease. Our case report is illustrative of an MTX-related NHL in an autoimmune patient. Conclusion. Withdrawal of MTX in a patient with lymphoma is reasonable before initiating chemotherapy, but observation for early regrowth of disease is necessary.

Detection of a mammographically occult invasive lobular breast carcinoma by PET/CT in a patient with lymphoma.

We present a case of invasive lobular breast carcinoma which was detected incidentally by positron emission tomography/computed tomography (PET/CT) in a patient with lymphoma, although occult on the subsequent mammogram. This 60-year-old female, with a history of non-Hodgkin lymphoma, underwent PET/CT imaging for routine follow-up which demonstrated a new hypermetabolic focus in the right breast suspicious for malignancy. Further workup showed no mammographic abnormality, but ultrasound-guided biopsy demonstrated this to be an unsuspected primary breast carcinoma. This case indicates that evaluation of the breasts is important to include in PET/CT interpretation, and abnormalities should be diligently pursued despite lack of mammographic correlation.