Despite improvements in first-line therapies, published results on the treatment of relapsed adult acute lymphoblastic leukemia (ALL) show that prognosis is still poor. The aim of the present ...retrospective analysis of the German Multicenter Study Group for Adult ALL was to identify prognostic factors and options for improvement. A total of 547 patients with a median age of 33 years (range, 15-55) experiencing their first relapse (406 vs 141 shorter or longer than 18 months from diagnosis) were evaluated. The aim of salvage therapy was to achieve a complete remission (CR) with subsequent a stem cell transplantation (SCT). The CR rate (assessed in Philadelphia chromosome– and BCR-ABL–negative ALL without CNS involvement) after the first salvage in relapse after chemotherapy (n = 224) was 42%. After failure of first salvage (n = 82), the CR rate after second salvage was 33%. In relapse after SCT (n = 48) the CR rate after first salvage was 23%. The median overall survival after relapse was 8.4 months and survival was 24% at 3 years. Prognostic factors for survival were relapse localization, response to salvage, performance of SCT, and age. Overall survival appeared superior compared with previously published studies, likely because of the high rate of SCT in the present study (75%). Further improvement may be achieved with earlier relapse detection and experimental approaches in early relapse. The study is registered at www.clinicaltrials.gov as NCT00199056 and NCT00198991.
Objectives Cell therapy may offer novel therapeutic options for chronic ischemic heart disease. In a clinical trial, we first assessed the feasibility and safety of intramyocardial CD133+ bone marrow ...cell injection together with coronary artery bypass grafting (CABG). We then tested the hypothesis that CABG plus CD133+ cell injection would result in better contractile function than CABG alone. Methods Fifteen patients took part in the safety study, followed by 40 patients who underwent either CABG with cell therapy or CABG alone. Bone marrow was harvested from the iliac crest one day before surgery, and purified CD133+ progenitor cells were injected in the infarct border zone during the CABG operation. LV function was measured by echocardiography and myocardial perfusion by SPECT. Results In the safety study, no procedure-related complications were observed for up to 3 years. LV injection fraction (LVEF) increased from 39.0% ± 8.7% preoperatively to 50.2% ± 8.5% at 6 months and 47.9% ± 6.0% at 18 months ( F = 6.03, P = .012). In the efficacy study, LCEF rose form 37.4% ± 8.4% to 47.1% ± 8.3% at 6 months in the group with CABG and cell therapy ( F = 24.16, P < .0001) but only from 37.9% ± 10.3% to 41.3% ± 9.1% in the CABG-only group ( F = 7.72, P = .012). LVEF was significantly higher at 6 months in the group with CABG and cell therapy than in the CABG-only group ( P = .03). Similarly, perfusion of the infarcted myocardium improved more in patients treated with CABG and cell therapy than in those treated with CABG alone. Conclusion Intramyocardial delivery of purified bone marrow stem cells together with CABG surgery is safe and provides beneficial effects, though it remains to be seen whether thewe effects produce a lasting clinical advantage.
Rituximab has been shown to be active in follicular lymphoma (FL), both as monotherapy and in combination with chemotherapy. We conducted a randomized trial comparing mitoxantrone, chlorambucil, and ...prednisolone (MCP) chemotherapy plus rituximab with MCP alone.
Previously untreated patients with stage III or IV CD20+ indolent or mantle cell lymphoma were randomly assigned to either eight 28-day cycles of MCP plus rituximab (R-MCP; n = 181) or eight cycles of MCP alone (n = 177). All patients who achieved a complete or partial remission were treated with interferon maintenance until relapse. Herein, we report the results from the primary analysis population of patients with FL, who constituted the majority of patients (56%) recruited to the trial (n = 201; R-MCP, n = 105; MCP, n = 96).
Rates of overall and complete response were significantly higher in the R-MCP arm than the MCP arm (overall response, 92% v 75%, respectively; P = .0009; complete response, 50% v 25%, respectively; P = .004). With a median follow-up time of 47 months, median event-free survival (EFS) and progression-free survival (PFS) times were significantly prolonged with R-MCP compared with MCP (EFS, not reached v 26 months, respectively; P < .0001; PFS, not reached v 28.8 months, respectively; P < .0001), and overall survival (OS) was significantly improved with R-MCP compared with MCP (4-year OS rate, 87% v 74%, respectively; P = .0096).
The R-MCP regimen significantly improves complete and overall response rates, EFS, PFS, and OS in patients with previously untreated advanced FL, without a clinically significant increase in toxicity.
Implantation of bone-marrow stem cells in the heart might be a new method to restore tissue viability after myocardial infarction. We injected up to 1.5×10
6 autologous AC133+ bone-marrow cells into ...the infarct border zone in six patients who had had a myocardial infarction and undergone coronary artery bypass grafting. 3–9 months after surgery, all patients were alive and well, global left-ventricular function was enhanced in four patients, and infarct tissue perfusion had improved strikingly in five patients. We believe that implantation of AC133+ stem cells to the heart is safe and might induce angiogenesis, thus improving perfusion of the infarcted myocardium.
Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony-stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells ...(MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man.
Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11 MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(-1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to 1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control), and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control).
G-CSF and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.
Abstract Patients lose protective immunity to vaccine-preventable diseases after haematopoietic stem cell transplantation (HSCT). Therefore, revaccination of HSCT recipients represents an important ...strategy for reducing morbidity and mortality associated with these infections. Since there is little consensus on vaccine recommendations and practices for allogeneic HSCT recipients with active chronic graft-versus-host disease (GVHD) the German–Austrian–Swiss-Consensus Conference on Clinical Practice in Chronic GVHD developed an immunization schedule with the aim to provide optimal patient care. The proposed vaccine recommendations include immunization against Haemophilus influenzae type b , pertussis, pneumococci, meningococci, tetanus, diphtheria, hepatitis A and B, measles, mumps and rubella, influenza, poliomyelitis, varicella-zoster virus, human papilloma virus, and tick-borne encephalitis with a particular focus on vaccination of patients with active chronic GVHD.
In the prospective study 02/96 on primary GI lymphoma, we have collected data on histology, clinical features, and treatment results. In particular, in stages I and II localized primary gastric ...lymphoma (PGL), our objectives were to reduce treatment intensity and to confirm our hypothesis from study 01/92, which maintained that an organ-preserving approach is not inferior to primary surgery.
Patients receiving radiotherapy and/or chemotherapy were stratified for histologic grade, stage, and whether surgery had been carried out or not (as decided by each participating center). Patients with aggressive PGL received six cycles of CHOP-14 (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by involved-field radiotherapy (40 Gy). Patients with indolent PGL (including patients experiencing treatment failure with antibiotic therapy for Helicobacter pylori) were treated with extended-field radiotherapy. The volume depended on stage. The irradiation dose was 30 Gy, followed by a boost of 10 Gy (the latter omitted after complete resection) to the tumor region.
Seven hundred forty-seven patients were accrued. Of these patients, 393 with localized PGL were treated with radiotherapy and/or chemotherapy only or additional surgery between December 1996 and December 2003. The survival rate at 42 months for patients treated with surgery was 86% compared with 91.0% for patients without surgery.
In this nonrandomized study (02/96), we reproduced the previous results of study 01/92 showing no disadvantage for an organ-preserving treatment. Therefore, primary stomach resection should be questioned.
Treosulfan was introduced recently as a conditioning agent for allogeneic blood stem-cell transplantation. The favorable nonhematologic toxicity profile at 3 x 10 g/m(2) was the basis for dose ...escalation in this prospective, multicenter trial.
Fifty-six patients with various hematologic malignancies who were not eligible for standard conditioning were treated with one of three doses: 10 g/m(2), 12 g/m(2), or 14 g/m(2) of intravenous treosulfan, which was administered on days -6 to -4 combined with fludarabine 30 mg/m(2) on days -6 to -2. Patients in complete remission (CR; 42%) or non-CR (58%) received grafts from matched related (47%) or matched unrelated (51%) donors; one patient had a mismatched related donor (2%).
No engraftment failure occurred. Overall, extramedullary toxicity and the nonrelapse mortality rate at 2 years (20%) were low and did not increase with dose. Cumulative incidence of relapse/progression reached 31%. The overall survival and progression-free survival rates were 64% and 49%, respectively, in the total study population. An inverse dose dependency of relapse incidence was indicated in the subgroup receiving transplantations from matched related donors (P = .0568).
Treosulfan-based conditioning was feasible at all three doses. The 3 x 14 g/m(2) dose was selected for additional studies, because it combines desired characteristics of low toxicity and a low relapse rate.
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