Facial-auditory nerve oxalosis

I CORRESPONDENCE AUTOLOGOUS BONE MARROW TRANSPLANTATION IN NONHODGKIN'S LYMPHOMA To the Editor: The report by Hurd et al (Am J Med 1988; 85: 829-834) is undoubtedly an important contribution to the problem of therapy of "poorprognosis" non-Hodgkin's lymphoma (Rosenberg SA: Autologous bone marrow transplantation in non-Hodgkin's lymphoma. N Engl J Med 1987; 316: 1541-1542). Their series of 17 patients received intensive therapy followed by autologous bone marrow transplantation (ABMT) of cryopreserved marrow that was treated in vitro by a combination of three monoclonal antibodies and complement. These monoclonal antibodies (BA-1, BA2, and BA-3) effectively lyse tumor cells ex vivo, and reactivity of the patients' malignant tissue with at least one monoclonal antibody was a prerequisite for inclusion in the study. The authors found that the outcome was largely determined by the status of disease at the time of t r a n s p l a n t a t i o n , whereas prior marrow involvement or the grade of lymphoma did not appear to affect disease-free survival. Surprisingly, however, no mention was made of the reactivity of the patients' neoplastic cells with the monoclonal antibodies as an additional and potent factor. According to the data presented in their Table

I, reactivity with two or three monoclonal antibodies was strikingly related to a favorable response and outcome. Of the eight patients in both the refractory/relapsing and the responding groups whose cells reacted with at least two of the monoclonal antibodies, six remained alive (288 to 1,674 days after transplantation) and only two died (one death due to early sepsis before engraftment, and not due to a relapse). Conversely, of the five patients in both groups whose cells reacted with only a single monoclonal antibody, none remained alive and their median survival was 143 days, as compared to 559 days in the monoclonal'antibodies-reactive group. These groups of patients were small but the differences were highly significant (p <0.025, by two-tailed Fisher's exact test). Four patients whose cells reacted with a single monoclonal antibody but who did not undergo testing with the other monoclonal antibodies were excluded for the purpose of this analysis. Future verification of these observations may indicate not only that occult bone marrow contamination by malignant cells is common and is an important factor in determining the outcome of ABMT in non-Hodgkin's lymphoma, but also that prior in vitro testing with the panel of monoclonal antibodies can identify

patients most likely to benefit from this mode of treatment. AMI SCHATTNER, M.D. YITZHAL BERNER, M.D. Kaplan Hospital Rehovot, Israel and Hadassah Medical School Jerusalem, Israel Submitted April 20, 1989, and acceptedOctober 6, 1989

FACIAL-AUDITORY NERVE OXALOSIS To the Editor: Palmer et al (Am J Med 1989; 87: 91-92) noted that patients with ethylene glycol toxicity may present with cranial nerve deficits. As two of the neurologists involved in the evaluation of the two reported cases, we believe additional important points must be made. In a reference omitted from the article by Palmer et al, Factor and Lava [1] declared delayed facial diplegia a fourth clinical stage of ethylene glycol poisoning. In two of the four reported cases, hearing loss had also occurred [1-4]. These cases combined with the two cases of Palmer et al illustrate the following point: it is not that cranial nerve deficits per se are seen in ethylene glycol poisoning but that facial diplegia, frequently with deafness, occurs characteristically. In fact, the concurrence of cerebrospi-

Figure1. Postmortem sample from patient with ethylene glycol toxicity shows dense refractile crystal deposition (arrowheads) along the subarachnoid portions of the seventh and eighth cranial nerves. January1990 The AmericanJournalof Medicine Volume88

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nal fluid changes, increased serum anion gap acidosis, renal failure, facial diplegia, and deafness may be a diagnostic pentamerism. Also important is that ethylene glycol is usually believed to exert its toxic effects through aldehyde metabolites and not through calcium oxalate crystal deposition [5]. However, the subacute timing of the cranial nerve deficits would be atypical for aldehyde metaboliterelated toxicity. Postmortem material from Patient 1 of Palmer et al, the first autopsy material available from a patient with this clinical variant, showed dense refractile crystal deposition along the subarachnoid portions of the seventh

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and eighth cranial nerves (Figure 1). This strongly implies in situ crystal deposition as the pathogenic process--a unique mechanism of toxicity for a distinct clinical variant. We suggest facial-auditory nerve oxalosis as a name for this fourth clinical stage of ethylene glycol toxicity, since it describes the clinical features and probable mechanism. In summary, it is not cranial nerve deficits as much as seventh and eighth cranial nerve deficits that provide "a clue to the diagnosis of ethylene glycol poisoning." The occurrence of these cranial nerve problems denotes a distinct clinical variant t h a t appears to

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have a unique mechanism of toxicity. BRITT ANDERSON, M.D. Biloxi, Mississippi 39531 Q. MARK ADAMS, M.D. Arlington, Texas 76015 1. Factor SA, Lava NS: Ethylene glycol intoxication: a new stage in the clinical syndrome. NY State J Med 1987; 87: 179-180. 2. Berger JR, Ayyar DR: Neurological complications of ethylene glycol intoxication--report of a case. Arch Neurol 1981; 38: 724-726. 3. Fellman DM: Facial diplegia following ethylene glycol ingestion (letter). Arch Neurol 1982; 39: 739. 4. Mallya KB, Mendis T, Guberman A: Bilateral facial paralysis following ethylene glycol ingestion. Can J Neurol Sci 1986; 13: 340-341. 5. Parry MF, Wallach R: Ethylene glycol poisoning. Am J Med 1974; 57: 143-150. Submitted August 23, 1989, and accepted October 9, 1989