Treatment‐related leukemia in Hodgkin's disease: A multi‐institution study on 75 cases

Abstract

Hematological and cytogenetic characteristics of 75 cases of therapy-related acute non lymphoid leukemia (t-ANLL) occurring in Hodgkin's disease (HD) are analysed in this multi-institution study. Combined radio and chemotherapy had been given in 88 per cent of patients, either as adjuvant (44 per cent) or as salvage modality (44 per cent). Radiotherapy alone and chemotherapy alone had been given in 3 per cent and 9 per cent respectively. Eighty per cent of patients were in remission of HD and 71 per cent off-therapy while developing leukemia. The median latent time from remission of HD to leukemia was 34 months. The myeloblastic variety of leukemia accounted for 43 per cent of total cases; the myelomonocytic and monocytic for 17 per cent and 4 per cent, the promyelocytic and erythroblastic variants for 5 per cent and 7 per cent of t-ANLL. Twenty four per cent of cases were unclassifiable; one of these was TdT-positive. Dysplastic features of erythrocytic line were invariably present with circulating erythroblasts; defects of granulocytes, circulating megathrombocytes and micromegakaryocytes were also present. Bone marrow hypoplasia and marked fibrosis were documented in 47 per cent and 30 per cent of cases. Preleukemia heralded overt leukemia in 73 per cent of cases; 37 per cent had refractory anemia with no excess of blasts; 16 per cent of preleukemias were unclassifiable. Cytogenetics revealed chromosome abnormalities in 83 per cent of cases; 72 per cent presented chromosome 5 and/or 7 monosomy or partial deletion (5q- or 7q-) of the long arm (94 per cent in the combined modality therapy group). In 3 cases, a pure monosomy 7 was observed; in none 5q-alone. Response rate to conventional therapy was 14 per cent; low and high-dose cytarabine were of little benefit. Long-term CR (28 + and 16 + months) was achieved in 2 cases with allogeneic bone marrow transplantation (BMT) as first-line therapy. A better knowledge of t-ANLL in HD and new therapies, including BMT, may improve the prognosis of this late complication of intensive HD treatment.

Secondary hematological malignancies following breast cancer treatment

“…Only a trend in a higher CR rate (74 vs. 51%, P \ 0.08) was observed for secondary AML following BC [42]. In contrary to observations in secondary AML in Hodgkin lymphoma patients [69], previous exposure to alkylating agents did not modify treatment response [42].…”

Acute nonlymphocytic leukemia: onset after treatment for Hodgkin's disease

“…Therapy-related MDS arises following exposure to alkylating agents with or without radiotherapy for primary cancers [4,6,16,25] and is an important long-term complication of bone marrow transplantation [28]. Secondary therapy-related MDS is characterized by bone marrow dysfunction [22,25], anemia and thrombocytopenia [8,22,30], karyotypic abnormalities [33,35,37] (especially loss of some or all chromosomes 5 and/or 7), and rapid transformation to acute leukemia [22] refractory to antileukemic therapy [18,19,23,34]. The hematological and cytogenetic findings relevant to our series of secondary MDS are in agreement with those in previous reports [34,37].…”

Therapy-Related Myelodysplastic Syndrome

“…7,8 However, some authors reported it difficult to classify therapy-related disease by FAB criteria, mainly because many cases show marked multilineage dysplasia but fewer than 5% blasts in the blood or bone marrow, findings that do not fit well into any of the FAB subgroups. [19][20][21] Such cases could be classified by the WHO criteria as refractory cytopenia with multilineage dysplasia (RCMD), yet in that classification scheme, therapy-related acute myeloid leukemia (t-AML) and t-MDS are simply grouped together as a single syndrome (t-AML/MDS) and included with AML. 9 The WHO system further recognizes 2 subtypes of t-AML and t-MDS depending on the previous chemotherapy received by the patient (alkylating agent-related vs topoisomerase-II inhibitor-related disease).…”