Risk Of Secondary Acute Leukemia Research Articles

Secondary Acute Leukemia in Sarcoma Patients: A Population-Based Study

Tocompare rates of secondary acute leukemia between sarcoma patients and the general population, using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registry, and to examine whether various patient, tumor, and treatment factors were associated with development of a secondary acute leukemia. Patients with a primary diagnosis of connective tissue malignancy between 1973 and 2008 in the SEER database were included. Multivariable competing risk analysis was used to determine risk factors associated with subsequent development of acute leukemia. Using observed-to-expected ratios, we compared incidence rates of secondary acute leukemia between sarcoma patients and the general population. A total of 72,945 patients were identified, with median follow-up of 131months. On multivariable competing risk analysis, factors associated with increased risk of secondary acute leukemia included receipt of radiation therapy (hazard ratio [HR] 1.67, P=.02), distant disease (HR 2.67, P=.004), male gender (HR 1.53, P=.03), year of diagnosis (HR 0.98, P=.049), and Ewing sarcoma histology (HR 9.95, P < .0001) and osteosarcoma histology (HR 5.06, P=.0001). The observed-to-expected ratio for development of a secondary acute leukemia was 3.67 (95% confidence interval [CI] 1.95-6.28), 3.41 (95% CI 2.73-4.20), and 1.6 (95% CI 1.38-8.19) for acute lymphocytic leukemia, acute myeloid leukemia, and acute monocytic leukemia, respectively. The 10-year cumulative incidence of secondary acute leukemia for patients who did and did receive radiation therapy was 0.3% versus 0.1% (P=.02). Patients treated for sarcoma, in particular those with Ewing sarcoma and osteosarcoma histology, seem to have a higher incidence of secondary acute leukemia as compared with the general population. Treatment factors including radiation therapy and chemotherapy seem to play a role in this increased risk, although the absolute incidence nevertheless remains very small.

Family history of breast or ovarian cancer modifies the risk of secondary leukemia after breast cancer: Results from a population‐based study

We evaluated the impact of a family history of breast/ovarian cancer on the risk of secondary leukemia following breast cancer. At the Geneva cancer registry, we identified 4,397 patients diagnosed with invasive breast cancer between 1990 and 2004. Patients were followed up for leukemia until the end of 2005. Family history was categorized as positive in patients with >or=1 first- or second-degree relative with breast/ovarian cancer. We compared leukemia rates in patients with positive and negative family histories with those expected in the general population, generating standardized incidence ratios (SIRs). With Cox regression analysis, we calculated adjusted risks of secondary leukemia in patients with familial risks compared to those without it. Breast cancer patients had a significantly increased risk of secondary acute leukemia (SIR 3.2, 95% CI: 1.2-6.9) but not of chronic leukemia (SIR 1.6, 95% CI: 0.6-3.5). Among patients with a positive family history (n = 1.125, 25.6%), the SIRs were 5.7 (95% CI: 1.2-16.6) for acute and 5.2 (95% CI: 1.4-13.3) for chronic leukemia. Among breast cancer patients, family history was independently associated with leukemia [adjusted hazard ratio (HR(adj)) of 3.2, 95% CI: 1.1-9.2, among patient with vs. without family history]. The effect of family history was stronger for chronic leukemia (HR(adj): 11.6, 95% CI 1.3-104.7) than for acute leukemia (HR(adj) 1.6, 95% CI: 0.4-6.6). Breast cancer patients with a family history of breast/ovarian have an increased risk of secondary leukemia, both compared to the general population as well as to breast cancer patients without family histories. This excess risk is largely due to the increased risk of secondary chronic leukemia.

Risk of Acute Leukemia Post-Autologous Stem Cell Tranplant (ASCT) for Hodgkin's Lymphoma (HL) Depends on Choice of Salvage Chemotherapy and Use of Radiation.

Background: Late treatment-related mortality (TRM) and second cancers (SC) have an important impact on the long-term outcome of patients (pts) with HL. The optimum salvage regimen (based on efficacy and acute and late toxicity) as part of second-line therapy with ASCT is not known. Pts undergoing ASCT are at high risk of both solid tumors and leukemia (Proc ASCO 2007 abstr #8016). We analyzed our single-institution data to determine the contribution of the components of salvage therapy to leukemia risk post-transplant.Methods: From Dec 1986 to Nov 2005, 321 pts with relapsed/refractory HL after doxorubicin-based primary chemotherapy (+ involved/extended field radiation [RT]: 46%) received salvage chemotherapy to best response, followed by etoposide 60 mg/kg day-4 and melphalan 160–180 mg/m2 [day-3] supported by autologous bone marrow (46%), mobilized PBSCs (49%) or both (5%) [day 0]. 27% received involved field RT post-ASCT. Risk of treatment failure and second cancers was estimated using competing risks methods. Leukemia risk with time was determined by cumulative incidence function.Results: Patient characteristics: male: 61%; median age 33 yrs (range16–67). No. of salvage regimens pre-ASCT: 1: 76%; 2: 19%; ≥3: 5%. Salvage chemotherapy: BCNU, etoposide, cytarabine, melphalan (miniBEAM, [MB]) 162 (50%); cisplatinum-based regimens (dexamethasone, cytarabine, cisplatin [DHAP] or gemcitabine, dexamethasone, cisplatin [GDP]) 128 (40%); other 10%. Disease status post-salvage chemotherapy: CR 28%, PR 66%. With a median follow-up of 4.7 yrs post-ASCT (range 1–17), estimates of OS, PFS and disease relapse are 53%, 53% and 46% at 5 years, and 39%, 51% and 48% at 10 yrs. The cumulative incidence of treatment-related death (from toxicity or SC) continues to increase from 9% (6–13) at 3 years to 15% (11–20) 10 yrs post-ASCT. The probability of SC is 5% (2.8–7.8) at 3 years and 12% (7.9–16.7) at 10 years (leukemia risk: 7%, solid tumour risk: 5%). There have been a total of 154 deaths, 104 from progressive HL alone and 37 from treatment-related events - 14 (9%) of these were from SC with no evidence of relapsed HL. There were an additional 11 deaths from a combination of causes (relapsed HL and other), 9 (6%) of these were related to SC. 30 SC were identified, 12 solid tumors and 18 AML/MDS. The risk of secondary acute leukemia differs according to salvage chemotherapy received - 0.9% (0.1–6.2) and 3.4% (0.7–15.1) at 3 and 10 yrs respectively in DHAP/GDP pts, compared to 4.6% (2.2–9.4) and 9.1% (5.4–15.3) in pts treated with MB [p=0.051]. Pts who received radiation (pre- or post-ASCT) have a leukemia risk of 4% (1.8–8) at 3yrs increasing to 8.5% (4.9–14.4) at 10yrs, while pts who never received radiation had a stable leukemia risk of 1.8% (0.3–12%) [p=0.19].Conclusions: In this single institution experience with HL pts undergoing ASCT with a consistent salvage therapy strategy, long-term survivors have an on-going increasing risk of SC and leukemia which contributes to late mortality. Specific components of therapy appear to influence this risk. Our observation of an unexpected increased risk of AML in HL patients receiving miniBEAM salvage prior to transplant suggests that the contribution of other salvage regimens to late adverse effects warrants further investigation.

Persistent abnormalities in red cell parameters following treatment of lymphoma.

Patients who have recovered from malignant lymphoma are at an increased risk of secondary acute leukemia (AL), and overt AL is frequently preceded by a myelodysplastic syndrome. Although the statistical risk is significant, only a minority of the patients will be so affected. We have reviewed peripheral blood counts of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) treated in the Departments of Hematology at the Edith Wolfson and Chaim Sheba Medical Centers, Israel. Included were only those who went into a complete remission and remained lymphoma free for extended periods. There were 85 patients with HD and 36 with NHL. In both groups peripheral blood counts at diagnosis were within the normal range. A prolonged follow-up (> 4 y), during which no further treatment was given, revealed a sustained increment over time of MCV (delta MCV) both in HD and NHL. A persistent monocytosis in HD patients was also evident. delta MCV was larger in HD. The difference at the end of the follow-up period was as follows: 10.1 fl + 11.8 in HD vs 5.0 fl + 6.2 in NHL, (P < 0.001). In addition, a significant loss of the normal correlation between the MCV and levels of hemoglobin was seen at the last follow-up. The change in MCV was present in all treatment groups, its magnitude increasing from radiotherapy to chemotherapy to combined radio chemotherapy. This trend is in analogy to the risk of secondary AL which is lower in NHL vs HD. Furthermore, it is lowest post radiotherapy and highest when both treatment modalities are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Splenectomy and the increasing risk of secondary acute leukemia in Hodgkin's disease.

Following irradiation alone, secondary acute nonlymphocytic leukemia (ANLL) is uncommon; following chemotherapy alone, the risk is increased, but not as much as when combined modality treatments are used. Because ANLL seems more likely to occur in splenectomized patients, attention is focused on an unexpected association between splenectomy and the risk of secondary leukemia. The risk of ANLL was assessed in 503 patients with Hodgkin's disease (HD) homogeneously treated with combined modality therapy (mechlorethamine, vincristine, procarbazine, and prednisone [MOPP] plus radiotherapy). These patients were diagnosed from 1970 through 1984 and monitored until June 1991. ANLL was observed in one of 145 (0.69%) patients not splenectomized and in 21 of 358 (5.86%) splenectomized patients, demonstrating a significantly higher frequency of ANLL in the group of patients who underwent splenectomy. The group of patients who developed ANLL received a statistically greater number of MOPP courses than did the group not developing ANLL. ANLL was statistically more frequent in those patients who received more than four cycles of MOPP. Sex, symptoms, extent of radiotherapy, splenectomy, age, and number of MOPP courses were assessed for their impact on ANLL incidence by multivariate analysis. Cox's proportional hazards regression showed that splenectomy and, as previously described by others, the number of courses of MOPP are prognostic factors that increase the risk of secondary ANLL in HD patients treated with combined modality therapy. These data raise interesting questions regarding the possible role of the spleen in leukemia development.

Risk of secondary acute leukemia and preleukemia after Hodgkin's disease: the Institut Gustave-Roussy experience.

From 1960 to 1984, 871 patients were treated for Hodgkin's disease at the Institut Gustave-Roussy. Twenty-six percent of the cohort were treated with radiotherapy (RT) alone, 6% with chemotherapy (CT) alone, and 68% with a combination of RT and CT, either at first line or for salvage treatment. MOPP chemotherapy was given to 42% of the patients. Overall, 19 secondary acute leukemias or preleukemias were observed, 3 of them after extended RT alone, the other 16 after a combination of RT and MOPP. Among the alkylating agents used, only nitrogen mustard (mechloretamine) was shown in a multivariate analysis to be significantly associated (P less than 0.001) with an increased risk of secondary leukemia. A dose response was observed, with the risk relative to general population incidence rates being 45 in patients having been treated with 1-59 mg (total dose) of nitrogen mustard, 211 in those treated with 60-119 mg, and 636 in those treated with greater than or equal to 120 mg. No other factors were found to be associated with leukemia risk. The 10-year cumulative incidence of leukemia was zero in patients treated with limited RT alone, 2.4% in those treated with extended RT alone, 0% in those treated with a combination of RT and CT without nitrogen mustard, and 12.4% in those treated with RT + nitrogen mustard. Whether other alkylating agents give a similar result remains to be determined; these data suggest that the use of nitrogen mustard at a higher total dose than 60 mg is questionable in the treatment of Hodgkin's disease.