Effective presentation of tumor antigens is fundamental to strategies aimed at enrolling the immune system in eradication of residual disease after conventional treatments. Myeloid malignancies provide a unique opportunity to derive dendritic cells (DCs), functioning antigenpresenting cells, from the malignant cells themselves. These may then co-express leukemic antigens together with appropriate secondary signals and be used to generate a specific, antileukemic immune response. In this study, blasts from 40 patients with acute myeloid leukemia (AML) were cultured with combinations of granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor ␣, and development to DCs was assessed. After culture, cells from 24 samples exhibited morphological and immunophenotypic features of DCs, including expression of major histocompatibility complex class II, CD1a, CD83, and CD86, and were potent stimulators in an allogeneic mixed lymphocyte reaction (MLR). Stimulation of autologous T-cell responses was assessed by the proliferative response of autologous T cells to the leukemic DCs and by demonstration of the induction of specific, autologous, antileukemic cytotoxicity. Of 17 samples, 11 were effective stimulators in the autologous MLR, and low, but consistent, autologous, antileukemic cytotoxicity was induced in 8 of 11 cases (mean, 27%; range, 17%-37%). This study indicates that cells with enhanced antigen-presenting ability can be generated from AML blasts, that these cells can effectively prime autologous cytotoxic T cells in vitro, and that they may be used as potential vaccines in the immunotherapy of AML. (Blood. 2001; 97:2764-2771)
Lymphomatoid granulomatosis (LG) is a very rare, Epstein-Barr virus-associated lymphoproliferative disorder of B cells. Prognosis is poor, particularly after relapse and no curative treatment exists. We report the results of high-dose therapy and autologous stem cell transplantation (ASCT) or reduced-intensity conditioning and allogeneic stem cell transplantation (alloSCT) in patients with multiply relapsed LG. A European Group for Blood and Marrow Transplantation survey identified 10 patients who had received 9 ASCT and 4 alloSCT. All patients had active disease at the time of transplantation. With a median follow-up of 5.1 (range, 1.4 to 6.3) years, 6 patients are alive and disease-free. Two ASCT patients died of septicemia early after transplantation, and 1 committed suicide after being in continuous complete remission 19 months after ASCT. Another patient allografted 4 years after ASCT remained disease-free but died of severe graft-versus-host disease 3 months after alloSCT. High-dose therapy followed by ASCT and alloSCT are effective therapeutic options and should be considered in all patients with refractory and multiply relapsed LG.
Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) can stimulate megakaryopoiesis in vitro in some myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) patients. We assessed PEG-rHuMGDF combined with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin 3 (IL-3), IL6, stem cell factor (SCF) or erythropoietin in 40 MDS, 33 AML and 16 normal bone marrow samples. CD61-positive cells in suspension cultures increased with PEG-rHuMGDF alone in 20/25 RA + RAS, 11/14 RAEB + RAEBt and 29/33 AML cases. Further increases when IL-3 and/or SCF were added to PEG-rHuMGDF occurred in 14/20 RA + RAS, 8/13 RAEB + RAEBt and 18/26 AML cases. CFU-Mk growth was poor overall, but could be enhanced by PEG-rHuMGDF combinations in some patients. Stimulation of megakaryopoiesis by PEG-rHuMGDF can be augmented by IL-3 and SCF in many MDS and AML patients.
3550 Introduction: Older patients diagnosed with acute myeloid leukemia (AML) present the clinician with particularly difficult treatment decisions. A number of attempts have been made to develop algorithms to assist clinician decision making but these are not widely used. The United Kingdom Medical Research Council AML14 Trial failed to recruit to a randomization between intensive and non-intensive treatment approaches, suggesting that clinicians preferred to use clinical judgement when selecting patients for intensive chemotherapy despite the lack of evidence on how this should be done. Methods: Several published scoring systems were evaluated and two applied retrospectively to 54 consecutive patients older than 60 years old presenting with AML between January 2009 and December 2010 to three collaborating Hematology departments. In addition, the role of the peripheral blast count (less than versus equal to or more than 0.1×109/L), as a marker of degree of proliferation, in predicting outcome was assessed. Treatment decisions for all patients had been based on clinical assessment by a senior physician and discussion by a multidisciplinary team rather than on application of a scoring system. Patients received palliative care only (2), best supportive care (16), non-intensive (9) and intensive (27) chemotherapy. Results: Median overall survival was 5.5 months. A significant difference in survival (12.0 versus 3.2 months, p<0.005 log-rank test) was seen, irrespective of treatment received, between those with low (<6.9, equivalent to predicted treatment related mortality (TRM) of 3%) versus high (>6.9, equivalent to predicted TRM of 20%) scores using the AML Treatment-Related Mortality (AML-TRM) score (Walter RB et al, 2011, J.Clin Oncol. 29:4417), which was developed to predict risk of early death following induction chemotherapy in older patients. Despite the use of clinical assessment only, 65% of low risk patients by AML-TRM had received intensive chemotherapy; 70% of high risk patients had not received intensive chemotherapy. By contrast, the Hematopoetic cell transplantation - specific comorbidity index (HCT-CI) (Sorror ML et al, 2005, Blood 106:2912), developed to assess fitness for transplantation in younger patients, did not predict outcome in this patient group. A peripheral blast count of less than versus equal to or more than 0.1×109/L was found to predict outcome for patients who received best supportive care (Table 1). Four patients with peripheral blast counts equal to or more than 0.1×109/L who received non-intensive chemotherapy also showed poor survival (median 2.0 months). Conclusions: The previously validated AML-TRM score is a strong predictor of outcome in older patients with AML irrespective of treatment received. However, it is not clearly better than a treatment decision based on clinical assessment by an experienced physician. The peripheral blast count was a single parameter which could be used to influence treatment decisions. In this series, patients with peripheral blast counts less than 0.1×109/L, correlating with less proliferative disease, did at least as well with best supportive care as with intensive chemotherapy. These patients should be offered best supportive care unless a clear curative plan, including for example an allogeneic stem cell transplant after intensive chemotherapy, can be made. However, patients with a peripheral blast count equal to or more than 0.1×109/L did very badly with best supportive care only or with non-intensive chemotherapy and should be offered intensive chemotherapy where possible. Disclosures: No relevant conflicts of interest to declare.
Summary. Systemic mastocytosis is uncommon. Symptoms result from local infiltration and degranulation of mast cells. Reports in the literature describe successful use of interferon α and radiotherapy to produce reduction in symptoms and bulk of disease. We report a patient who responded to radiotherapy but not interferon α.
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