b'A Rare Cancer Prompts Sleuthing at the VA; New Options for MDSVA researchers solved a mystery involving younger veterans who developed unusual and deadly cancers. They determined that patients currently using certain drugs, thiopurines, had triple the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) on an adjusted basis compared to those never exposed.The risks resolved with discontinuation.By Annette M. BoylePHILADELPHIAThe researchers at the VA maytoproduceenoughhealthy,fullyfunctionalblood notwearSherlockHolmesdeer-stalkercaporcells. In AML, an excess number of myeloblasts or Colombos wrinkled raincoat, but their work as in- immature white blood cells interferes with the pro-vestigators requires the same tireless detective workduction of other types of blood cells and platelets. and determination to identify suspects and find theBoth conditions occur at the rate of 4.3 to 4.5 per bad actor. 100,000 patients years in the general population and In a case in point, a team at the Corporal Michael J.have low survival rates, less than 50% at three years Crescenz VAMC and the University of Pennsylvaniafor MDS and 28% at five years for AML. Perelman School of Medicine, both in Philadelphia,Previous studies of a potential connection between had cases of an unusual and deadly cancer and a sus- thiopurines and AML/MDS had been hampered by a pect drug with an extensive rap sheet but no solidsmall number of cases and an unusually young age for evidence linking it to the cancer. 1 the patients, two problems the VA researchers over-The link between the suspect, the thiopurine classcame with access to the nationwide VA cohort. The of drugs, and nonmelanoma skin cancers and lym- cohort has a median age of 64 years, in line with the phoma has been well documented. Investigation intomedian age at diagnosis for AML (68) and MDS (71). theirconnectiontourinarytractcancerisunder- The team identified 56,314 veterans with a diagnosis way.Thethiopurinesazathioprine,mercaptopu- of IBD over an 18-year period. Of those, 15,305 had rine, and thioguanine are commonly used to man- ever been exposed to thiopurines (TP). The study fol-agethesymptomsofinflammatoryboweldiseaselowed patients for a median of 9.7 years. During the (IBD), both ulcerative colitis and Crohns disease.study period, 107 patients developed AML/MDS, for Could these drugs also be instigators in the devel- a crude incidence rate of 18.7 per 100,000. opmentofmyelodysplasticsyndrome(MDS)andTwenty-one veterans developed AML/MDS while acute myeloid leukemia (AML) in the same patientreceiving thiopurines, all of whom also developed population? incident leukopenia in the two years prior to AML/The investigators combined MDS and AML intoMDS diagnosis. The majority had sustained leuko-one entity for their study because the myeloid stempenia in the lead up to their AML/MDS diagnosis. cell lineage is affected in both conditions and becauseThiswasaverysignificantfindingthatunder-MDS, which is also called preleukemia, transformslines the importance of monitoring WBC counts in into AML in about one-third of cases. MDS includespatients on TPs, especially among the elderly, the a range of disorders in which the bone marrow failsresearchers said. In light of our findings, if patients Continued on Page 27 u21'