The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantation for follicular lymphoma.

The impact of the follicular lymphoma (FL) histologic grade on outcomes after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) is unknown. We evaluated 219 consecutive patients with grades 1-3 FL who underwent HDT and ASCT at our center. Overall survival (OS), progression-free survival (PFS), relapse and non-relapse mortality (NRM) was estimated for each grade after controlling for other predictive factors. The number of patients with grades 1, 2 and 3 FL was 106 (48%), 75 (34%) and 38 (17%), respectively. Five-year outcome estimates for the entire cohort included 60% OS, 39% PFS and 46% relapse (median follow-up=7.8 years). PFS and relapse were nearly identical among patients with grade 3 FL versus grades 1-2 FL after adjusting for other contributing factors (hazard ratio (HR)=0.90, P=0.68; HR=1.07, P=0.80, respectively). The hazard for mortality (HR=0.70, P=0.23) and NRM (HR=0.33, P=0.07) was non-significantly lower among patients with grade 3 FL compared to patients with grades 1-2 disease. Factors associated with inferior PFS included elevated lactate dehydrogenase (HR=1.52, P=0.03), chemoresistance (HR=1.82, P=0.02), > or =2 prior therapies (HR=1.8, P=0.03) and prior radiation (HR=1.99, P=0.003). These data suggest that the histologic grade of FL does not impact PFS or relapse following HDT and ASCT.

Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue.

PURPOSE: Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND METHODS: Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty-nine patients received therapeutic infusions of single-agent (131)I-anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi [10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support. RESULTS: Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic dose-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS). CONCLUSION: Myeloablative (131)I-anti-B1 RIT is relatively well tolerated when given with autologous stem-cell support and often results in prolonged remission durations with few late toxicities.

Comparison of the L10M consolidation regimen to an alternative regimen including escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a Southwest Oncology Group Study.

The effectiveness of intensive post-remission chemotherapy regimens for adult patients with acute lymphoblastic leukemia (ALL) is limited by both a high rate of disease recurrence and a substantial incidence of treatment toxicity. To evaluate a potentially more effective and less toxic approach, we conducted a multicenter phase III trial of consolidation therapies comparing the standard L10M regimen with one combining the brief, intensive L17M regimen and escalating methotrexate (MTX) and L-asparaginase (L-asp). Patients over age 15 with previously untreated ALL were eligible. Induction therapy included vincristine, prednisone, doxorubicin, cyclophosphamide and intrathecal methotrexate administered over 36 days. Patients who achieved complete remission (CR) were randomized to receive consolidation with either the L10M regimen or with DAT (daunomycin, cytosine arabinoside, 6-thioguanine) and escalating MTX and L-asp. The randomization was stratified by age, WBC and Ph chromosome status. Maintenance therapy was the same in both arms. Of 353 eligible patients, 218 (62%) achieved CR and 195 were randomized. The treatment arms did not differ significantly with respect to disease-free survival (DFS; P= 0.46) or overall survival (P= 0.39). Estimated DFS at 5 years was 32% (95% confidence interval (CI) 23-42%) in the L10M arm and 25% (95% CI 16-33%) in the DAT/MTX/L-asp arm. In each arm, 4% of patients died of toxicities (infection in all but one case). Infections and nausea/vomiting were somewhat more common in the L10M arm (occurring in 68% and 53% of patients respectively) than the DAT/MTX/L-asp arm (56% and 33%). The DAT/MTX/L-asp consolidation regimen was associated with some reduction in nonfatal toxicities, but no significant improvement in DFS, overall survival or non-relapse mortality when compared to the standard L10M regimen.

Phase I study of a humanized anti-CD11/CD18 monoclonal antibody in multiple sclerosis.

OBJECTIVE: To evaluate the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of a humanized anti-CD11/CD18 monoclonal antibody (Hu23F2G) in patients with multiple sclerosis. METHODS: In this phase I uncontrolled dose escalation study, patients (n = 24) with primary or secondary progressive multiple sclerosis received single intravenous infusions of Hu23F2G (0.01 to 4.0 mg/kg). Study parameters included safety, pharmacology, immunogenicity, and brain magnetic resonance imaging (MRI). RESULTS: Hu23F2G had few adverse effects, but 2 cases of urinary tract infection and 2 cases of gingivitis did occur. Transient leukocytes developed in some subjects receiving > or = 1.0 mg/kg. The pharmacokinetic response was nonlinear, with the area under the curve increasing out of proportion to the increase in dose. The mean terminal half-life increased with dose and was 21.9 (SD, 12.8) hours at the 4.0 mg/kg dose. High saturation (> 80%) of CD11/CD18 on circulating leukocytes was achieved with doses > or = 0.2 mg/kg. The duration of high leukocyte saturation was dose-dependent, persisting for more than a week at the 4.0 mg/kg dose. A marked decrease in leukocyte migration in response to cutaneous inflammation was observed. Antibodies against Hu23F2G were not detected. The neurologic examinations were stable except for 1 subject who had worsening weakness associated with an infection. No significant changes were noted on brain MRI scans. CONCLUSIONS: Hu23F2G was tolerated at doses that achieved high degrees of leukocyte CD11/CD118 saturation with in vivo inhibition of leukocyte migration. Because this phase I study was not designed to determine the clinical efficacy of Hu23F2G, further studies are needed.

Samarium-153-EDTMP biodistribution and dosimetry estimation.

Fifty-two patients were treated with single doses of 153Sm-EDTMP in a Phase I escalating dose protocol for palliation of bone pain from metastatic prostate carcinoma. Samarium-153 (T1/2 46.3 hr), maximum beta-particle energies 810 keV (20%), 710 keV (30%), 640 keV (50%), gamma photon 103 keV (28%), was complexed to the tetraphosphonate chelate, EDTMP. Five groups of patients were treated at doses of 1.0, 1.5, 2.0, 2.5, and 3.0 mCi/kg to evaluate toxicity from treatment. Patients were screened prior to treatment and followed after treatment with 99mTc-MDP bone scans. Biodistribution data on this group of patients were acquired and showed rapid uptake of 153Sm-EDTMP into bone with complete clearance of nonskeletal radiotoxicity by 6-8 hr. Also included are complete sets of dosimetry estimations on an additional seven patients who received 0.5 mCi/kg 153Sm-EDTMP Ca++ as part of a multiple dose therapy trial. Estimated radiation absorbed doses to bone surfaces averaged 25,000 mrad/mCi (6686 Gy/MBq), and urinary bladder doses averaged 3600 mrad/mCi (964 Gy/MBq).

Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial.

Samarium-153-ethylenediaminetetramethylene phosphoric acid (EDTMP), a bone-seeking radiopharmaceutical, was given to prostate cancer patients in a dose escalation protocol for pain palliation to determine the maximally tolerated dose. Fifty-two patients with hormone refractory prostate cancer with bony metastases were treated with doses beginning at 0.5 mCi/kg (18.5 MBq/kg), escalating in 0.5-mCi (18.5 MBq) increments to 3.0 mCi/kg (111 MBq/kg). Pain response after treatment was assessed as well as hematologic and serum chemistry parameters. Pain palliation with a mean duration of 2.6 mo was present in 74% of the patients. Toxicity was exclusively hematologic at the highest dose levels. No infectious or bleeding complications occurred, with 45 of the 52 (86%) patients demonstrating complete hematologic recovery. Patients receiving higher doses had significantly greater reductions in serum prostate specific antigen and serum prostatic acid phosphatase levels. The patients receiving greater doses also showed a trend toward improved survival.

A phase I study of induction chemotherapy for older patients with newly diagnosed acute myeloid leukemia (AML) using mitoxantrone, etoposide, and the MDR modulator PSC 833: a southwest oncology group study 9617.

Older patients with acute myelogenous leukemia (AML) have overexpression of P-glycoprotein (Pgp+), and this has been shown to correlate quantitatively with therapeutic outcome. Since Pgp-mediated efflux of cytotoxic drugs can be inhibited by the cyclosporine analogue, PSC 833, we investigated the use of this agent with a 5-day mitoxantrone/etoposide regimen in patients over age 55 with newly diagnosed AML. Previous studies suggested a 33% incidence of grade IV/V non-hematologic toxicity with the use of mitoxantrone 10 mg/M(2) and etoposide 100 mg/M(2), each for 5 days, in this patient population. Since PSC 833 alters the pharmacokinetic excretion of MDR-related cytotoxins, this phase I dose-finding study was performed to identify doses of mitoxantrone/etoposide associated with a similar 33% incidence of grade IV/V non-hematologic toxicity, when given with PSC 833. Mitoxantrone/etoposide (M/E) doses were escalated in fixed ratio from a starting dose of M: 4 mg/M(2) and E: 40 mg/M(2), to M: 7 mg/M(2) and E: 70 mg/M(2), in successive cohorts of eight patients each. PSC 833 was well tolerated and the MTD of this M/E regimen with PSC 833 in this population was M: 6 mg/M(2) and E: 60 mg/M(2). The complete response (CR) rate for all patients was 50% (15/30) and was considerably higher for de novo than for secondary AML. These data suggest that the addition of PSC 833 to an M/E regimen for older patients with untreated AML is well tolerated but requires a reduction in M/E dosing to avoid increased toxicity.

Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies.

The purpose of this study was to determine the maximal tolerated dose of thiotepa administered with busulfan 12 mg/kg and melphalan 100 mg/m2 followed by autologous stem cell transplantation in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose busulfan 12 mg/kg, melphalan 100 mg/m2 and escalating doses of thiotepa 450-550 mg/m2 followed by infusion of cryopreserved autologous peripheral blood stem cells (n = 26) or marrow (n = 2). The maximum tolerated dose was determined to be busulfan 12 mg/kg, melphalan 100 mg/m2 and thiotepa 500 mg/m2. Two of three patients receiving thiotepa 550 mg/m2 experienced grade 3 colitis. Twenty patients were enrolled at the maximum tolerated dose and the incidence of grade 3-4 regimen-related toxicity and mortality was 10% and 5%, respectively. Ninety-five per cent of patients experienced grade 1-2 mucositis, 50% grade 1-2 gastrointestinal toxicity, 35% grade I hepatic toxicity and 20% experienced grade 1-2 skin toxicity. The median time to achieve a granulocyte count of 0.5 x 10(9)/I was 10 days (range 8-20 days) and platelet transfusion independence was 10 days (range 1-26 days). Five of ten patients with stage 4 refractory breast cancer achieved a complete and two a partial remission with a complete response rate of 50% and a overall response rate of 70%. In conclusion, busulfan, melphalan and thiotepa can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy sensitive malignancies are warranted.

Autologous stem cell transplantation for Hodgkin's disease: busulfan, melphalan and thiotepa compared to a radiation-based regimen.

We evaluated prognostic factors and treatment outcome of patients with relapsed/refractory Hodgkin's disease (HD) receiving autologous stem cell transplantation (ASCT). In total, 92 patients received total body irradiation, cyclophosphamide and etoposide (TBI/CY/E) (n=42) or busulfan, melphalan and thiotepa (Bu/Mel/T) (n=50) supported with ASCT. A total of 33 (66%) patients receiving the Bu/Mel/T regimen had a prior history of dose-limiting irradiation. Mucositis, hepatic and pulmonary toxicities were the main causes of morbidity and mortality, irrespective of the conditioning regimen. The transplant-related mortality was 15%. With a median follow-up of 6 years (range 2.5-11), the cumulative probabilities of survival, event-free survival (EFS) and relapse at 6 years were 55, 51 and 32%. The 6-year Kaplan-Meier (KM) probabilities of EFS for patients with less advanced disease (patients in first chemotherapy-responsive relapse or second remission (n=42)) and more advanced disease (all other patients (n=50)) were 60 and 44%. No differences in toxicities and efficacy between the conditioning regimens were found. ASCT is an effective treatment for patients with refractory/relapsed HD. Female patients and patients with less advanced disease at transplant had a better outcome. Patients with prior irradiation benefited from the Bu/Mel/T regimen.

Efficacy of high-dose therapy and autologous hematopoietic stem cell transplantation for non-Hodgkin's lymphoma in adults 60 years of age and older.

High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the optimal treatment for patients with relapsed aggressive non-Hodgkin's lymphoma (NHL). HDT, however, is often reserved for relatively younger patients due to limited data in older adults. We treated 53 patients aged 60 years and older (median age 62 years, range 60.3-67.7 years) with HDT and ASCT for NHL at our centers. Forty-four patients (83%) had aggressive histology, 75% had chemosensitive disease and all had failed anthracycline therapy. Conditioning regimens included busulfan, melphalan, and thiotepa (45%); cyclophosphamide (CY), etoposide (VP-16), and total body irradiation (TBI) (30%); CY and TBI (15%); and other regimens (10%). Estimated 4-year overall survival (OS), progression-free survival, and treatment-related mortality (TRM) were 33%, 24% and 22%, respectively. A multivariable analysis demonstrated that patients with chemosensitive disease (P = 0.03) and < or =3 prior regimens (P = 0.03) had superior survival. Four-year OS in patients with chemosensitive disease was 39% vs 15% in patients with chemoresistant disease. Reduced TRM was associated with the CY, VP-16 and TBI regimen (P = 0.02). HDT therapy with ASCT may result in prolonged survival and potential cure for about a quarter of elderly patients, and for almost 40% with chemosensitive disease. Optimal conditioning regimen selection may further improve outcome by reducing TRM. Age alone should not be used to exclude patients from receiving myeloablative therapy with ASCT.

Interleukin-2 after autologous stem cell transplantation for hematologic malignancy: a phase I/II study.

The success of autologous stem cell transplantation (ASCT) for hematologic malignancy is limited largely by a high relapse rate. It is postulated that IL-2 administered after ASCT may eliminate minimal residual disease and thereby reduce relapses. A phase I/II study was performed to identify a regimen of IL-2 (Chiron) that could be given early after ASCT in phase III trials. In the phase I study, beginning a median of 46 days after ASCT for hematologic malignancy, cohorts of three to four patients received escalating doses of 'induction' IL-2 of 9, 10, or 12 x 10(6) IU/m2/day for 4 or 5 days by continuous i.v. infusion (CIV), followed by a 4-day rest period, and then 1.6 x 10(6) IU/m2/day of maintenance IL-2 by CIV for 10 days. The maximum tolerated dose (MTD) of induction IL-2 was 9 x 10(6) IU/m2/day x 4. In the phase II study, 52 patients received the MTD. Eighty percent of patients completed induction IL-2. Most patients exhibited some degree of capillary leak. One patient died of CMV pneumonia and one died of ARDS. Maintenance IL-2 was well tolerated. In the phase I/II study, 16 of 31 patients with non-Hodgkin lymphoma (NHL), 3/8 with Hodgkin disease (HD), 4/17 with AML, and 4/5 with ALL remain in CR. Two of six multiple myeloma (MM) patients remain in PR. Although the regimen of IL-2 identified had significant side-effects in some patients, it was well tolerated in the majority of patients. Phase III prospectively randomized clinical trials are in progress to determine if this IL-2 regimen will decrease the relapse rate after ASCT for AML and NHL.

High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer.

The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.

Phase II study of high-dose busulfan, melphalan and thiotepa with autologous peripheral blood stem cell support in patients with malignant disease.

The purpose of this study was to determine the toxicities and potential effectiveness of high-dose busulfan, melphalan and thiotepa (Bu/Mel/TT) followed by autologous peripheral blood stem cell (PBSC) infusion in patients with a variety of diseases. A phase II clinical trial of Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC infusion in 104 patients with breast cancer (n = 48), malignant lymphoma (n = 25), ovarian cancer (n = 13), multiple myeloma (n = 7) and other malignancies (n = 11) was performed. Sixty-two patients were treated in an academic medical center and 42 in a community cancer center. Grade 3-4 regimen-related toxicities occurred in 14% of patients, causing regimen-related mortality in six (6%) patients with an overall transplant-related mortality of 9%. Transplant-related deaths occurred in 6/62 patients (10%) treated in an academic medical center and in 3/42 (7%) treated in a community cancer center. Complete remissions (CR) were achieved in 1/17 (6%) patients with refractory stage IV breast cancer, 4/4 patients with responsive stage IV breast cancer, 6/13 (46%) with more-advanced lymphoma and 4/4 with less-advanced lymphoma. These patients are alive and disease-free a median of 712, 279, 461 and 404 days after transplant, respectively. Nineteen of 22 patients with stage II-III breast cancer remain alive and disease-free a median of 365 days after transplant. Complete remissions were also seen in 4/9 patients with ovarian cancer and 3/7 with multiple myeloma. The Bu/Mel/TT regimen followed by autologous PBSC infusion is associated with acceptable morbidity and mortality, appears to have significant activity in patients with breast cancer and is well tolerated in the adjuvant setting of stage II-III breast cancer. Bu/Mel/TT also appears to have significant activity in patients with lymphoma, multiple myeloma and possibly ovarian cancer. Further phase II-III studies are warranted in patients with these and other malignancies.

Lymphoproliferative disorders presenting as mediastinal neoplasms.

Lymphoproliferative disorders may present in any organ of the body. The mediastinum is an uncommon location for presentation of these heterogeneous disorders, but involvement of the mediastinum may be the sole site of disease for several aggressive lymphomas. Both Hodgkin's disease and non-Hodgkin's lymphoma may present in the mediastinum. The most common types of non-Hodgkin's lymphoma involving the mediastinum include lymphoblastic lymphoma and mediastinal large cell lymphoma. These lymphomas most commonly develop in the anterior mediastinum but may be seen in the middle and posterior mediastinum. Symptoms associated with a mediastinal presentation of a lymphoproliferative disorder are often attributable to compression of mediastinal structures (eg, superior vena cava syndrome) or invasion of thoracic structures such as the pericardium or pleura. Although staging can be performed with routine imaging studies, surgical intervention is often required to ensure accurate histologic diagnosis of these lymphomas. Once a diagnosis has been established, therapeutic modalities usually include chemotherapy and/or radiotherapy.

Intrathoracic granulocytic sarcomas.

Recent trends in the treatment of intrathoracic granulocytic sarcoma (IGS) call for an overview of its radiographic manifestations. Nine patients from our institution and a review of 41 from the literature provide the basis of our conclusions on the typical and atypical appearance of IGS. Of the nine patients with IGS, all had chest radiographs, five had computed tomographic (CT) scans, and one had magnetic resonance (MR) scans. Radiographic studies and medical records were examined to establish the site and appearance of IGS. Three cases were histologically proved; in the others, the diagnosis was based on clinical presentation and response to chemotherapy. The mediastinum was the most common site of involvement (six of nine cases). A focal mass or mediastinal widening was visible on chest radiographs, and a focal mass or diffuse infiltration or replacement of fat was visible on chest CT. Less common sites of involvement were the lungs (two cases), the pleura (two), the pericardium (two), and the hilar (two). Mediastinal or hilar mass or mediastinal widening is the characteristic finding in IGS. Less common manifestations such as pleural and pericardial effusions and lung opacities should be confirmed histologically, since fluid or tissue is readily accessible.

Declining rates of treatment-related mortality in patients with newly diagnosed AML given 'intense' induction regimens: a report from SWOG and MD Anderson.

Less-intense remission induction regimens for adults with newly diagnosed acute myeloid leukemia (AML) aim to reduce treatment-related mortality (TRM), here defined as death within 4 weeks after starting induction therapy. This assumes that TRM rates are similar to the 15-20% observed 20 years ago. Herein we test this assumption. We examined TRM rates in 1409 patients treated on SWOG (Southwest Oncology Group) trials and 1942 patients treated at MD Anderson (MDA) from 1991 to 2009. Eighty-eight percent of SWOG patients received '3+7' or regimens of similar intensity while 92% of the MDA patients received ara-C at 1.5-2.0 g/m(2) daily × 3-5 days+other cytotoxic agents. We examined the relationship between time and TRM rates after accounting for other covariates. TRM rates between 1991 and 2009 decreased from 18-3% in SWOG and 16-4% at MDA. Multivariate analyses showed a significant decrease in TRM over time (P=0.001). The decrease in TRM was not limited to younger patients, those with a better performance status or a lower white blood cell count. Though our observations are limited to patients treated with intensive therapy at SWOG institutions and MDA, the decrease in TRM with time emphasizes the problem with historical controls and could be considered when selecting AML induction therapy.

Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study.

The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18-5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23-5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09-0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis.

Molecular alterations of the IDH1 gene in AML: a Children's Oncology Group and Southwest Oncology Group study.

Recent whole-genome sequencing efforts led to the identification of IDH1(R132) mutations in acute myeloid leukemia (AML) patients. We studied the prevalence and clinical implications of IDH1 genomic alterations in pediatric and adult AML. Diagnostic DNA from 531 AML patients treated on Children's Oncology Group trial COG-AAML03P1 (N=257), and Southwest Oncology Group trials SWOG-9031, SWOG-9333 and SWOG-9500 (N=274), were tested for IDH1 mutations. Codon R132 mutations were absent in the pediatric cohort, but were found in 12 of 274 adult patients (4.4%, 95% CI 2.3-7.5). IDH1(R132) mutations occurred most commonly in patients with normal karyotype, and those with FLT3/ITD and NPMc mutations. Patients with IDH1(R132) mutations trended toward higher median diagnostic white blood cell counts (59.2 x 10(9) vs 29.1 x 10(9) per liter, P=0.19) than those without mutations, but the two groups did not differ significantly in age, bone marrow blast percentage, overall survival or relapse-free survival. Eleven patients (2.1%) harbored a novel V71I sequence alteration, which was found to be a germ-line polymorphism. IDH1 mutations were not detected in pediatric AML, and are uncommon in adult AML.