title: Risk of therapy-related secondary leukemia in Hodgkin lymphoma: the Stanford University experience over three generations of clinical trials.
abstract: OBJECTIVE
  To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials.
  
  
  METHODS
  Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS.
  
  
  RESULTS
  Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy.
  
  
  CONCLUSIONS
  Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).
authors.affiliation: Stanford University Medical Center, 875 Blake Wilbur Dr, CC-2338, Stanford, CA 94305, USA.
authors.forename: Michael Zach
authors.initials: MZ
authors.lastname: Koontz
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Horning
authors.forename: Raymond
authors.initials: R
authors.lastname: Balise
authors.forename: Peter L
authors.initials: PL
authors.lastname: Greenberg
authors.forename: Saul A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Richard T
authors.initials: RT
authors.lastname: Hoppe
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects; D002140:California / Q000453:epidemiology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002986:Clinical Trials as Topic; D003606:Dacarbazine / Q000009:adverse effects; D016208:Databases, Factual; D004317:Doxorubicin / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008466:Mechlorethamine / Q000009:adverse effects; D008558:Melphalan / Q000009:adverse effects; D008727:Methotrexate / Q000009:adverse effects; D009190:Myelodysplastic Syndromes / Q000453:epidemiology* / Q000209:etiology; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology; D011241:Prednisone / Q000009:adverse effects; D011344:Procarbazine / Q000009:adverse effects; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012189:Retrospective Studies; D012306:Risk; D014747:Vinblastine / Q000009:adverse effects; D014750:Vincristine / Q000009:adverse effects
chemical_list: D001761:Bleomycin; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin; D008558:Melphalan; D011241:Prednisone; D008727:Methotrexate