Treatment of Therapy-Related Leukemia and Myelodysplastic Syndrome

Kantarjian, Hagop M.; Estey, Elihu H.; Keating, Michael J.

doi:10.1016/s0889-8588(18)30259-4

Cited by 97 publications

(78 citation statements)

References 89 publications

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“…38 The remaining cytogenetic abnormalities found in our patients, that is, trisomy 13 and t(1;7), are more rarely described in secondary MDS/AML patients. [37][38][39] In conclusion, our results show that the type and intensity of pre-transplant chemotherapy affect progenitorcell yield, hematological recovery, and transplant-related toxicity. We found an independent association between high cumulative doses of etoposide and CD34 þ cell collection, platelet engraftment, and TRM.…”

Section: Discussionmentioning

confidence: 57%

Effect of cumulative etoposide doses on the outcome of autologous peripheral-blood progenitor-cell transplantation for lymphoma

Martı́n

Pérez‐Simón

Caballero

et al. 2004

Bone Marrow Transplant

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Summary:Studies evaluating the effects of previous chemotherapy on stem-cell yield and hematological recovery after autologous peripheral-blood progenitor-cell transplantation (PBPCT) have shown conflicting results. We have retrospectively analyzed 103 consecutive lymphoma patients treated with the BEAM regimen and autologous PBPCT. The impact of the different chemotherapeutic drugs (cumulative doses) on stem-cell yield and transplant-related toxicity was investigated. Highly significant differences in platelet recovery (420 Â 10 9 /l) were observed between patients receiving less or more than 750 mg/m 2 of etoposide before transplant (15 vs 29 days, P ¼ 0.001), and between patients receiving less or more than 1.2 Â 10 6 /kg CD34 þ cells (27 vs 14 days, Po0.001). Differences in neutrophil engraftment between groups were not clinically significant. Pre-transplant cumulative doses of etoposide 4750 mg/m 2 were associated with low CD34 þ cell collections on multivariate analysis. The actuarial incidence of transplant-related mortality (TRM) was 14% at 5 years. Pre-transplant cumulative doses of etoposide 4350 mg/m 2 and previous administration of procarbazine were found to be independent prognostic factors for TRM.

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Section: Discussionmentioning

confidence: 57%

Effect of cumulative etoposide doses on the outcome of autologous peripheral-blood progenitor-cell transplantation for lymphoma

Martı́n

Pérez‐Simón

Caballero

et al. 2004

Bone Marrow Transplant

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“…30 While, in general, the prognosis of sAML occurring after topoisomerase II inhibitor treatment is poor, 31 there are controversial reports about the prognosis in patients with balanced translocations t(8;21), t(15;17) or inv(16) after topoisomerase II inhibitor treatment. Some investigators reported these cytogenetic abnormalities as favorable with the same response, and survival as de novo AML, 32,33 but others reported a poor outcome. 7,31,34 One patient in our study with AML M3 t(15;17) received a second autologous transplant and is now more than 3 years disease-free from both breast cancer and AML.…”

Section: Discussionmentioning

confidence: 99%

Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

Kröger

Damon

Zander

et al. 2003

Bone Marrow Transplant

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Summary:The incidence of secondary myelodysplasia/acute myeloid leukemia (AML) was retrospectively assessed in an international joint study in 305 node-positive breast cancer patients, who received mitoxantrone-based high-dose chemotherapy (HDCT) followed by autologous stem cell support as adjuvant therapy. The median age of the patients was 57 years (range 22-67). In all, 268 patients received peripheral blood stem cells, and 47 patients received autologous bone marrow. After a median followup of 57 months (range 10-125), three cases of secondary AML (sAML) were observed, resulting in a cumulative incidence of 0.94%. One case of sAML developed 18 months after HDCT (FAB M3) The karyotype was translocation 15;17 and, after induction therapy, the patient underwent autologous stem cell transplantation, and is in complete remission (CR) of both breast cancer and AML. The second patient developed AML (FAB M4eo with inversion 16) 5 months after HDCT. This patient achieved CR after induction therapy, but died of infectious complication. A third patient developed AML (FAB M4) 6 months after HDCT. She achieved CR after induction therapy, but relapsed and expired 28 months after diagnosis of AML. sAML after mitoxantrone-based HDCT is a possible, but rare complication in breast cancer patients. Bone Marrow Transplantation (2003) 32, 1153-1157. doi:10.1038/sj.bmt.1704291 Keywords: high-dose chemotherapy; adjuvant therapy; breast cancer; mitoxantrone; secondary AML Secondary myelodysplasia (MDS) or acute myeloid leukemia (AML) in breast cancer patients is a rare but wellknown long-term complication of prior chemotherapy or radiation therapy as adjuvant therapy. 1-3 Specific risk factors are the combinations of chemotherapy and radiation therapy, the cumulative dose of alkylating agents and the duration of therapy. 2 Two different types of treatmentrelated leukemia can be distinguished. The first type results from prior therapy with alkylating agents or radiation therapy, and occurs after a latency period of 5-7 years. This type of AML is often preceded by a preleukemic period of MDS. Nearly 90% of the patients with alkylating agentrelated MDS or AML show clonal chromosome aberrations including monosomy or deletions on chromosomes 5 and/or 7 or complex aberrations involving chromosomes 3, 12, 17, and 21. 4 The second type of therapy-related leukemia is induced by topoisomerase II-targeted drugs like etoposide, anthracyclines or, recently, anthracenediones. [5][6][7] This type of AML usually occurs after a median of 2 years and is not preceded by a myelodysplastic syndrome. According to the French-American-British (FAB) classification, more frequently, M4 or M5 subtype is observed and cytogenetic analysis showed a high frequency of rearrangements of the chromosome band as 11q23, translocation (t)(8;21), t(15;17), inversion 16 (inv(16)) or t(8;16), as in de novo AML. 5,8 Recently, several studies indicated that adjuvant chemotherapy consisting of the anthracenedione mitoxantrone, a topoisomerase II-targeted drug, may induce sec...

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“…MDS may occur as a consequence of marrow injury caused by chemotherapeutic agents or radiation used to treat prior benign or malignant conditions. [3][4][5][6][7] More commonly, MDS may occur as a primary disorder, in which no ascertainable cause for the disease can be identified. Even in the absence of leukemic evolution, most patients with MDS succumb to infection or transfusion-related complications, such as platelet alloimmunization or iron overload.…”

Section: Introductionmentioning

confidence: 99%

Primary myelodysplasia occurring in adults under 50 years old: a clinicopathologic study of 52 patients

et al. 2002

Leukemia

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Although myelodysplastic syndromes (MDSs) are generally thought to be diseases of elderly patients, younger patients also have rarely been diagnosed with MDS. This is a report of the clinical, morphologic and cytogenetic features of 52 cases of primary MDS occurring in adults under the age of 50 years. Cases secondary to chemotherapy or radiotherapy were excluded. There were 31 males and 21 females. The median age at presentation was 39 years (range, 18 to 49 years). The interval between onset of symptoms and diagnosis was brief (median, 4 weeks; range, 1-32 weeks). Of the 49 patients for whom information about duration of symptoms was available, 13 (27%) were asymptomatic. Forty-two (81%) of the patients were classified using FAB criteria for blood and bone marrow morphology: refractory anemia (RA), 11; refractory anemia with ringed sideroblasts (RARS), four; refractory anemia with excess blasts (RAEB), 12; chronic myelomonocytic leukemia (CMML), three; refractory anemia with excess blasts in transformation (RAEB-T), 12 patients. Ten patients could not be categorized. Abnormalities involving chromosome 7 was the most frequent cytogenetic abnormality (31%). Partial chromosomal deletion and chromosome gain were also common abnormalities (22% and 9%, respectively). Translocations accounted for only 9% of the main cytogenetic abnormalities encountered in this patient population. For the 49 patients for whom information regarding AML transformation was available, 23 (47%) progressed to acute myeloid leukemia, with an overall median time to progression of 2 months (range 3 weeks to 3 years). In each category except for RARS, approximately half of the patients progressed, with a slightly less median time to progression in RAEB-T than for the other subtypes of MDS. Thirteen patients underwent bone marrow transplantation at the time of presentation of their disease. Leukemia (2002) 16, 623-631.

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Treatment of Therapy-Related Leukemia and Myelodysplastic Syndrome

Cited by 97 publications

References 89 publications

Effect of cumulative etoposide doses on the outcome of autologous peripheral-blood progenitor-cell transplantation for lymphoma

Effect of cumulative etoposide doses on the outcome of autologous peripheral-blood progenitor-cell transplantation for lymphoma

Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

Primary myelodysplasia occurring in adults under 50 years old: a clinicopathologic study of 52 patients

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