Myelopathy following intrathecal chemotherapy in a patient with extensive burkitt's lymphoma and altered immune status

A 30-year-old homosexual man presented with widespread Burkitt's lymphoma. On the basis of immunologic and viral studies, he was suspected of having the acquired Immune deficiency syndrome. Following chemotherapy that included Intrathecal cytosine arabinoside and methotrexate, brain stem edema, paraplegia, and an elevated cerebrospinal fluid level of myelin basic protein developed. Autopsy revealed vacuolar demyelination of spinal cord, brain stem, and cerebellum. The pathologic findings were similar to those reported to occur In myelopathy associated with intrathecal chemotherapy, but far more extensive. The contribution of the suspected acquired immune deficiency syndrome is unknown.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25727/1/0000284.pd

A Deletion Linked to a Poly(ADP-ribose) Polymerase Gene on Chromosome 13q33-qter Occurs Frequently in the Normal Black Population as Well as in Multiple Tumor DNA

The nuclear enzyme poly(ADP-ribose) polymerase (PADPRP) is thought to play a role in DNA recombination, replication, and repair. In view of the implication of these processes in tumorigenesis, and based on preliminary evidence which indicated the presence of an extraneous polymorphic restriction fragment for murine PADPRP loci in strains of mice susceptible to plasmacytomas, we investigated correlations between the restriction fragment length polymorphism of the PADPRP gene(s) and human Burkitt lymphoma. No increase in the frequency of polymorphisms on chromosome 1 (containing the active gene) or on chromosome 14 (a pseudogene) was observed. However, restriction fragment length polymorphism analysis of PADPRP sequences on chromosome 13 (either a processed pseudogene or a gene with extensive identity to PADPRP) revealed that of 19 DNA samples derived from endemic Burkitt lymphoma all contained at least one copy of a rare allele (B). Simple two-allele (A/B) polymorphisms in this PADPRP-like locus were identified by digestion with a number of restriction enzymes including Hindlll, PstI, Kpnl, and Mspl. These restriction fragment length polymorphisms always segregated together, suggesting that they identify a deletion within or close to the PADPRP sequences on chromosome 13, which we mapped precisely to 13q33-qter. Based upon family studies the A and B alleles were shown to be transferred in a Mendelian codominant fashion. Subsequently, this probe was used as a linkage marker to study the frequency of this deletion in various tumors including B-cell follicular lymphomas, small cell lung carcinomas, breast carcinomas, and colorectal carcinomas. In noncancer control populations, the frequency of this deletion was 3-fold higher among Blacks as compared to Caucasians. When DNA from various tumors was compared to normal DNA from racially appropriate noncancer controls, the frequency of this deletion was still 2- to 3-fold higher in the tumor DNA. Matched samples provided instances of tumor-specific loss of heterozygosity but also revealed that the predominant source of this deletion is the germ line, suggesting that the chromosome 13 region neighboring the PADPRP locus may harbor a gene whose loss may predispose individuals to malignancy. © 1990, American Association for Cancer Research. All rights reserved

Outcome of patients > age 40 with Burkitt Lymphoma (BL) treated with aggressive chemotherapuetic regimens: results from the international Burkitt Lymphoma collaborative group

BL is considered a highly curable tumor when treated with dose-intensive, multiagent chemotherapy including central nervous system prophylaxis. 60–90% of pediatric and young adult patients (pts) with BL achieve durable remission if treated appropriately. However, the outcome of older adults with BL is more uncertain. We first investigated the SEER database and determined that 57% of reported pts with BL are > age 40. We then performed a systematic review of published manuscripts describing outcome of adult pts (> age 15) with confirmed de novo BL (REAL/WHO defined and confirmed) treated in the modern therapeutic era. Of 33 manuscripts, 17 were excluded due to small sample size (< 10 pts), inclusion of pts with HIV, inclusion of pts with alternate histologies, or utilization of CHOP-like therapy. Corresponding authors of the remaining 16 manuscripts were contacted to provide details on outcome of pts > age 40 for inclusion in a database, and full data is available from 12 manuscripts (10 prospective; 2 retrospective). 470 total adult BL pts ages 15–79 were treated, and 183 (39%) were > age 40. Pts > age 40 had significantly inferior outcomes in 10 of the 12 series. Treatment regimens included intensive short duration therapy (4 series; total N=212; > 40 N=93); ALL-like therapy (6 series; total N=182; > 40 N=62) and ASCT as part of induction therapy (2 series, total N=76; > 40 N=28). The median overall survival at 2 years (OS) for all pts treated with short duration therapy was 71%, and for pts > age 40 was 39%. The OS for all pts treated with ALL-like therapy was 51%, and for pts > age 40 was 40%. Pts > age 40 treated with ASCT as part of induction regimens had somewhat better outcomes (median OS 62%), however this represents a small number of pts who may have been subject to more rigorous selection criteria. We conclude that pts > age 40 with BL are significantly underrepresented in the published clinical trials. Even when these pts are treated with appropriate intensive chemotherapy, the OS is inferior compared to published outcomes in younger pts, and is similar to OS survival historically observed with CHOP chemotherapy alone (40%). Future efforts should evaluate whether BL in older adults has unique biological features. Novel therapeutic regimens, with decreased toxicity, targeting the older majority pts with BL are required