Secondary acute myeloid leukemia and myelodysplasia after autologous peripheral blood progenitor cell transplantation

Abstract

Secondary myelodysplastic syndrome (MDS) and acute leukemia (AL) are well-known complications of antineoplastic therapy. The incidence of these serious complications after autologous hematopoietic transplantation ranges from 1.1% to 24%. Prior chemotherapy is its most likely cause, but other variables related to these long-term complications are seriously discussed. There is evidence that priming of progenitor cells isolated from peripheral blood with chemotherapy is also related to a higher risk of secondary MDS/AL. Whether progenitor cells isolated from bone marrow or peripheral blood after mobilization only with cytokines are related to higher risk is a controversial issue. In this paper, we analyze the incidence and variables related to these complications in a series of 99 patients diagnosed with lymphoma or multiple myeloma who underwent autologous transplantation using hematopoietic progenitors isolated from peripheral blood mobilized with granulocyte colony-stimulating factor (G-CSF). The probability of MDS/AL in patients alive 5 years after transplant in our series is 8.58%, similar to that reported in other series using bone marrow grafts. The total dose of cyclophosphamide ( p=0.099), the number of chemotherapy cycles ( p=0.04) received before transplant, and the total dose of mononuclear cells infused at the time of transplant were the only variables associated with secondary MDS/AL. Autologous transplantation with progenitor cells isolated from peripheral blood after mobilization with cytokines has probability and risk factors for secondary MDS/AL development similar to bone marrow grafts when compared with other published series.

Autologous peripheral blood stem cell transplantation with BCVAC conditioning in childhood acute myeloid leukemia

“…The incidence of secondary MDS/AML after autologous transplantation ranges from 1.1 to 24%. 20 Recently, chemomobilization with etoposide was found to increase the risk of treatment-related MDS/AML in autologous transplantation. 21 Etoposide and Ara-C delivered before the mobilization of peripheral blood stem cell in our study may have increased the risk of secondary MDS.…”

Does autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients?

“…In support of this, several studies have identified a decreased dose of infused HSCs as a risk factor for t-AML/ MDS. 3,14,18 In addition, a recent report found an increased risk of t-AML/MDS in patients who required more than 5 days of apheresis, suggesting that a difficult stem cell harvest is a marker of marrow which has sustained significant genotoxic damage. 25 These observations support the notion that genotoxic damage initiated by pretransplant therapies may be amplified by the engraftment process, leading to the emergence of clonal abnormalities important in t-AML/MDS pathogenesis.…”

“…TBI 1,4,12,[15][16][17]20 Quantity of pre-transplant chemotherapy 2,12,13,15,18,25 Pre-transplant radiation therapy 4,8,9,16,25 Lower stem cell content/difficult stem cell collection 3,14,18,25 'Difficult' defined as requiring 45 days of apheresis. Pre-transplant alkylating agent exposure 2,13,20,22 PBSC product 5,6,11,20 Not found to be a risk factor by Sevilla et al 18 Trend (P ¼ 0.12) reported by Metayer et al 20 Time from diagnosis to transplant/number of relapses 9,12,14 Delayed platelet or ANC recovery post-transplant 2,14,19 Etoposide exposure 8,17 Exposure during priming chemotherapy or conditioning regimen. Pre-transplant fludarabine exposure 14,17 Refractory lymphoma 11,15 Abbreviations: AML/MDS ¼ acute myeloid leukemia and myelodysplasia; ASCT ¼ autologous stem cell transplantation; PBSC ¼ peripheral blood stem cell; TBI ¼ total body irradiation.…”

Pathophysiology of Acute Lymphoblastic Leukemia

“…The AML are hematologic malignancies characterized by the uncontrolled myeloid blast proliferation in the bone marrow and in peripheral tissues. (Sevilla et al, 2002) Differ according to the cytological, immunophenotypic and cytogenetic characteristics. (Paietta, 1995;Head, 1996) On the other hand the MDS are dis-hematopoietics processes of bone marrow, characterized by alteration in the maturation and differentiation of hematopoietic cell lines (with involvement of one, two or all three blood cell lineages) and in some cases, by the presence of bone marrow blasts, without showing acute leukemia criteria.…”