title: [Late myelotoxicity of high-dose chemotherapy according to the modified NHL-BFM-90 program in adult patients with diffuse large B-cell lymphoma].
abstract: OBJECTIVE
  to evaluate late myelotoxicity (MT) relate to high-dose chemotherapy (CT) according to the modified NHL-BFM-90 (mNHL-BFM-90) program in adult patients with diffuse large B-cell lymphoma (DLBCL).
  
  
  METHODS
  The results of a complex clinical, laboratory, and instrumental examination, including cytologic, histologic, and routine cytogenetic studies of the bone marrow (BM), were analyzed in 40 DLBCL patients treated according to the mNHL-BFM-90 program in the National Research Center for Hematology (NRCH), Ministry of Health of the Russian Federation (MHRF), in 2002 to 2009; among them, there were 20 men and 20 women (median age, 57 years). A comparison group consisted of 19 patients who had received high-dose СНОР/R-СНОР-21 CT in HRC, MHRF, in the same period of time; out of them, there were 8 men and 11 women (median age, 70 years). The median posttherapy follow-up period was 6 years. The results of BM studies were analyzed before and 5-10 years after treatment in complete remission. The cytological and histological studies of BM determined its cellularity, the sizes of erythroid, granulocytic, and megakaryocytic lineages, their ratios, the signs of dysplasia, and stromal dysplastic changes. Routine BM cytogenetic study was conducted to identify karyological problems. Only myelopoietic changes that had been revealed for the first time 5-10 years after completion of CT were kept in mind as late MT. Cases of baseline and post-CT changes and those of baseline and no post-CT changes were not taken into account.
  
  
  RESULTS
  Cytopenic syndromes (having no signs of myelopoietic lineage dysplasia or needing no blood component replacement transfusions) were revealed in 52% of the patients in the high-dose CT; thrombocytopenia amounted to 46%. In the late follow-up period, the patient group after high-dose mNHL-BFM-90 CT were found to have BM hypocellularity in 15 (38%) cases, a narrowing of erythroid and megakaryocytic lineages in 13 (33%) and 19 (48%) cases, respectively, and obvious secondary stromal changes in 17 (43%). The first 6 patients underwent routine BM cytogenetic study; all the patients were ascertained to have a normal karyotype; in this connection further BM study was stopped.
  
  
  CONCLUSIONS
  The late MT of high-dose mNHL-BFM 90 CT is statistically significantly higher than that of the standard CHOP/R-CHOP-21 therapy. However, signs of myelodysplastic syndromes and those of cytopenia requiring blood component transfusions were observed in none patient.
authors.affiliation: National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia.
authors.forename: E I
authors.initials: EI
authors.lastname: Dorokhina
authors.affiliation: National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia.
authors.forename: A U
authors.initials: AU
authors.lastname: Magomedova
authors.affiliation: National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia.
authors.forename: V N
authors.initials: VN
authors.lastname: Dvirnyk
authors.affiliation: National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Galtseva
authors.affiliation: National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia.
authors.forename: S A
authors.initials: SA
authors.lastname: Glinkina
authors.affiliation: National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia.
authors.forename: S M
authors.initials: SM
authors.lastname: Kulikov
authors.affiliation: National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia.
authors.forename: T N
authors.initials: TN
authors.lastname: Obukhova
authors.affiliation: National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia.
authors.forename: S K
authors.initials: SK
authors.lastname: Kravchenko
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D012426:Russia