Evidence Of Relapse Research Articles

Current Leukemia Free Survival After Tyrosine Kinase Inhibitor (TKI) for Chronic Myeloid Leukemia (CML): A New Method That Accounts for Restoring Response with Sequential TKI.

Abstract 2197Poster Board II-174 Background:Imatinib is very effective for patients with CML in chronic phase (CP). While some patients (pts) may fail therapy with imatinib (because of resistance or intolerance), effective salvage therapy is available with new generation TKI (dasatinib, nilotinib, bosutinib). Currently the efficacy of each therapy is judged by their individual impact on overall survival (OS) and event free survival (EFS). However calculations of EFS for a patient does not take into account the effect of successful salvage therapy with subsequent TKI. We therefore studied the current leukemia free survival (CLFS) to obtain a more accurate impression of the outcome of pts with CML treated with sequential TKI. Aim:To provide an accurate estimation of long-term outcome with TKI therapy among pts with CML treated with sequential TKI. Methods:All pts with CP CML who received imatinib after failure to interferon-alpha (IFN) therapy at MD Anderson Cancer Center (MDACC) were included n this analysis. Events were defined as failure to achieve a complete cytogenetic response (CCyR) by 12 months of therapy, loss of CCyR, or discontinuation of therapy because of toxicity or any other causes after 18 months without achieving CCyR. Pts who failed imatinib either went to a 2nd TKI or other class of therapy. EFS is defined as survival without evidence of relapse at anytime after imatinib while CLFS is defined as survival without evidence of leukemia relapse at the time of most recent assessment. Thus, a loss of response would count as an event, but a response to salvage therapy would “repair” that event. Pts receiving any therapy other than a TKI after imatinib or other TKI is counted as an irreparable failure. Results:Three hundred and five pts were treated at MDACC with imatinib after IFN failure. The median age was 54 years (range 23-81), 169 (55%) were males. Median time on IFN was 1.5 yrs (range 0.1-10 yrs). Best response to IFN was MCyR in 114 (37%), minor cytogenetic response in 35 (11%), and CHR in 86 (28%). Among the others, 15 were intolerant to IFN, 29 pts were resistant and 26 pts had an unknown response. Reasons for being off IFN included 141 (46%) cytogenetics .{/MAIN;137}resistance, 37 (12%) hematological resistance, 123 (40%) intolerance, and 4 (1%) unknown. On imatinib 201 (66%) pts achieved CCyR; 64 of them discontinued imatinib in CCyR because of toxicity or other reasons, none of 64 pts received a 3rd line TKI. 27 (9%) pts who failed imatinib were treated with another TKI and attained CCyR. Of them, 18 remained in CCyR, 7 eventually lost CCyR, and 2 lost CCyR but attained and maintained CCyR with a 3rd TKI. Seventy-seven (25%) pts failed imatinib and could not be salvaged either due to unavailability of a 2nd TKI or failure to achieve CCyR with a 2nd TKI. EFS for this patient population is 63% at 7 years, whereas the CLFS is 70%. Conclusion:CLFS can measure the actual benefit of TKI therapy by accounting for failures and subsequent responses. Despite the unavailability of 2nd generation TKI during the early part of the observation period, the CLFS of 71% at 7 years demonstrates the extraordinary benefit obtained with these agents alone or, when needed, in sequence. [Display omitted] Disclosures:Kantarjian:BMS: Research Funding; Novartis: Research Funding. Cortes:Novartis: Research Funding; BMS: Research Funding.

Aggressive surgical treatment of multidrug-resistant tuberculosis

Because extensively drug-resistant tuberculosis has emerged, adequate control of drug-resistant tuberculosis has become increasingly important. We report on our experience using liberal adjuvant resectional surgery as part of aggressive treatment for multidrug-resistant tuberculosis. We retrospectively reviewed the records of 56 consecutive patients who underwent pulmonary resections for multidrug-resistant tuberculosis between January 2000 and June 2007. There were 42 males and 14 females (mean age, 46 years; range, 22-64 years). Isolates were resistant to a mean of 5.6 drugs (range, 2-10 drugs). Multi-drug regimens employing 3 to 7 drugs (mean, 4.6 drugs) were initiated in all patients. Indications for surgery were a high risk of relapse for 37 patients, persistent positive sputum for 18, and 1 with associated empyema. The 56 patients underwent 61 pulmonary resections (3 completion pneumonectomies, 19 pneumonectomies, 33 lobectomies, and 6 segmentectomies). Bronchial stumps were reinforced with muscle flaps in 54 resections. Operative mortality and morbidity rates were 0% and 16%, respectively. All patients attained postoperative sputum-negative status. Relapse occurred in 5 patients; 3 were converted by a second resection, and 1 responded to augmentation of chemotherapy. Late death occurred for 2 patients without evidence of relapse. Among 54 survivors, 53 (98%) were considered cured. Surgical treatment that complements medical treatment has proved safe and efficacious for patients with multidrug-resistant tuberculosis. In an era with extensively drug-resistant tuberculosis, an aggressive treatment approach to multidrug-resistant tuberculosis continues to be justified until a panacea for this refractory disease is available.

Multiple Frame 18F-Fluorocholine or 11C-Acetate PET/CT Compared with Multi-modality MRI in Prostate Cancer Patients after Curative RT without Evidence of Relapse

To investigate the value of MRI and PET studies with either 18F-Fluorocholine (FCH) or 11C-acetate in patients with long term low and stable PSA levels after curative radiotherapy (RT) for prostate cancer. We aimed to test the ability of the above mentioned imaging modalities to differentiate benign radiation induced changes in the prostate from early local recurrences.

Accelerated R-COP: A Pilot Study for the Treatment of Advanced Low Grade Lymphomas that Has a High Complete Response Rate

This pilot study tested the hypothesis that dose intensity/dose density treatment may improve the response rate and remission duration in patients with advanced low grade lymphomas. Ten patients with low grade lymphomas: follicular lymphoma grades I and II, marginal zone lymphoma, and small cell lymphocytic lymphoma with progressive disease were studied. Patients had an ECOG performance of 0-2, and Stage III and IV disease. Both untreated and previously treated patients with progressive disease were eligible. Patients received a combination of rituximab 375 mg/m2, cyclophosphamide 1000 mg/m2, and vincristine 1.4 mg/m2 (up to a maximal dose of 2 mg), administered by intravenous infusion every two weeks, for ten treatments. prednisone 50 mg was administered every other day orally for thirty days and then tapered over the next thirty days. Granulocyte colony stimulating factor (G-CSF) was administered on days seven to ten following each cycle of chemotherapy. After 5 and 10 cycles, patients were evaluated for response that included imaging with Ct and pet scans. A total of 10 patients (7 untreated and 3 previously treated) were enrolled into this pilot study between May 2003 and July 2004. Untreated patients received an average of 8.3 cycles of therapy (range 5 to 10 cycles). Seven of 7 untreated patients achieved a complete response (CR), and 5 had not relapsed as of 32-43 months later. Previously treated patients received an average of 9.3 cycles of therapy (range 6 to 12 cycles). One of three previously treated patients achieved a complete response and has no evidence of relapse at 29 months. The other two heavily pretreated patients achieved partial responses, lasting 2 and 5 months. Toxicity was mild consisting mainly of parasthesias requiring attenuation of the vincristine dose. There were no instances of neutropenic fever requiring hospitalization. This program is well tolerated with a high CR rate, and may serve as a basis for future trials.

Adding a motivational interviewing pretreatment to cognitive behavioral therapy for generalized anxiety disorder: A preliminary randomized controlled trial

Seventy-six individuals with a principal diagnosis of generalized anxiety disorder (GAD) were randomly assigned to receive either an MI pretreatment or no pretreatment (NPT), prior to receiving CBT. Significant group differences favoring the MI-CBT group were observed on the hallmark GAD symptom of worry and on therapist-rated homework compliance, which mediated the impact of treatment group on worry reduction. Adding MI pretreatment to CBT was specifically and substantively beneficial for individuals with high worry severity at baseline. There was evidence of relapse at 6-month follow-up for high severity individuals who received MI-CBT, but significant moderator effects favoring the high severity MI-CBT group were again apparent at 12-months post-treatment. Pending replication in a more controlled test, these findings suggest that MI may be a promising adjunct to CBT for GAD for those of high severity, a group which has been less responsive to CBT in past research.

Successful Treatment of Membranous Glomerulonephritis with Rituximab in Calcineurin Inhibitor-Dependent Patients

Calcineurin inhibitors (CNIs) induce remission of proteinuria in most nephrotic patients with membranous glomerulonephropathy (MGN). However, 60% of patients become treatment dependent and are at risk of chronic nephrotoxicity. The aim of this study was to evaluate the efficacy of rituximab in patients with long-term dependence on CNIs. Thirteen patients with MGN, normal renal function, and proven dependence on CNIs, despite previous treatment with other immunosuppressant drugs, received a single trial of four weekly doses of rituximab (375 mg/m(2)). Outcome measures were the percentage of patients with CNI withdrawal and no evidence of relapse and the percentage of patients with complete or partial remission 30 mo after CNI withdrawal. After rituximab, proteinuria decreased significantly (2.5 +/- 0,76 basal versus 0.85 +/- 0.17 at 6 mo; P = .0003). CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse. After CNI withdrawal, GFR increased significantly (90.3 +/- 15 basal to 106.4 +/- 20 at 3 mo with a mean increase of 15.3% [range 0-20]). Three patients suffered a relapse of nephrotic proteinuria 19, 23, and 28 mo after rituximab treatment; all were successfully treated with a second course of rituximab. At 30 mo, all patients were in remission. In patients with MGN with long-term CNI dependence, rituximab can be an effective tool to overcome dependence on CNI, thus avoiding the risk of nephrotoxicity related to the chronic exposure to these drugs.

Inflammatory tumour of the prostate in a 4-year-old boy

An inflammatory tumour of the prostate is very rare in young boys without genital anomalies. We report a 4.5-year-old boy presenting with pollakisuria, dysuria, secondary urinary incontinence and decreased urine stream. Ultrasonography, magnetic resonance imaging and transrectal tumour biopsy justified the diagnosis of an inflammatory tumour of the prostate with a size of 5x3x5cm. Under antibiotic therapy the clinical symptoms disappeared within 6weeks. Three months later ultrasonography revealed a normal prostate with a residual midline cyst of 3x4mm. Follow-up examinations for 2years did not show any evidence of relapse. We believe that the inflammatory tumour can be explained by the embryologic development of the prostate and the persistence of an intraprostatic cyst.

Etoposide and mitoxantrone in newly diagnosed acute myeloid leukemia patients with persistent leukemia after a course of induction therapy with cytarabine and idarubicin

7073 Background: The goal of induction chemotherapy in acute myeloid leukemia (AML) is complete remission with restoration of normal bone marrow. If residual leukemia is present after the first course of induction therapy, patients receive a second course identical to the first or receive a non-cross resistant antileukemic regimen. Methods: In a retrospective study of adult patients with newly-diagnosed AML treated at the University of Pittsburgh Cancer Institute between December 2002 and May 2008, we evaluated the efficacy and toxicity of mitoxantrone (10 mg/m2/d) and etoposide (100 mg/m2/d), both administered intravenously within 5 days as second course therapy of patients not responding to first-course induction therapy with cytarabine and idarubicin. Univariate and multivariate associations between patient characteristics and complete response (CR) were assessed by logistic regression, with overall- and relapse-free survival estimated by Kaplan-Meier analysis. Results: 74 AML patients (mean age 56 years, range: 18–73 years) completed treatment with etoposide and mitoxantrone; 29 (39%) achieved CR. Lower CR rate was associated with unfavorable cytogenetic risk status at diagnosis and higher percent blasts prior to treatment with mitoxantrone and etoposide. Ten (14%) patients died due to infectious complications. No grade 3 or 4 hepatic toxicities were observed. One patient developed grade 3 cardiac toxicity. Median duration of neutrophil recovery following therapy in patients achieving CR was 29 days. Median overall survival was 9.0 months (95% CI 5.8–14.9 months). The 29 patients who achieved CR received postremission therapy: 16 of these eventually relapsed, while 4 others died without evidence of relapse. Median duration of relapse-free survival in these 29 patients was 11.0 months (95% CI: 9.0–19.3 months). Conclusions: Our study suggests that the combination of etoposide and mitoxantorne is an active and well-tolerated regimen as second-course therapy in newly diagnosed AML patients who have persistent leukemia after a first course of induction therapy with cytarabine and idarubicin. No significant financial relationships to disclose.

Diagnostic Value of Colonoscopy in Intestinal Diphyllobothrium latum Infection

Diphyllobothrium latum is an intestinal tapeworm that infests mammals. This report presents a case with small intestinal D latum infection that was successfully diagnosed and treated with endoscopy and Gastrografin. A 19-year-old man consulted the hospital because a tapeworm was spontaneously discharged in his feces. Colonoscopy disclosed a flat, yellow-white tapeworm at the terminal ileum (Figure A). To remove this tapeworm by endoscopy, it was grasped with a retrieval basket and gently and slowly pulled out through the anus to avoid tearing it (Figures B and C). However, it could not be completely removed (Figure D). The worm was identified as D latum on the basis of the morphologic characteristics. In 1986, Waki et al1Waki K. Oi H. Takahashi S. et al.Successful treatment of Diphyllobothrium latum and Taenia saginata infection by intraduodenal “Gastrografin” injection.Lancet. 1986; 2: 1124-1126Abstract PubMed Scopus (15) Google Scholar reported that a gastrointestinal contrast medium, Gastrografin, was effective for extirpating D latum, and several groups also reported its usefulness.2Fujita M. Koga H. Iida M. et al.The diagnostic yield of colonoscopy and the therapeutic value of intraduodenal amidotrizoic acid injection in intestinal Diphyllobothrium latum infection: report of a case.Am J Gastroenterol. 2002; 97: 2468-2470Crossref PubMed Scopus (9) Google Scholar, 3Ko S.B. Ohmiya N. Nakamura M. et al.Observation of deworming process in intestinal Diphyllobothrium latum parasitism by gastrografin injection into jejunum through double-balloon enteroscope.Am J Gastroenterol. 2008; 103: 2149-2150Crossref PubMed Scopus (6) Google Scholar Just after the diagnosis of the D latum infection, 200 mL of Gastrografin (Nihon Shering, Osaka, Japan) was injected into the third portion of duodenum by using an upper gastrointestinal fiberscope. It is important to inject Gastrografin immediately into the jejunum to treat such a tapeworm. Using endoscopy is an easy way to deliver large amounts of Gastrografin to the duodenum.3Ko S.B. Ohmiya N. Nakamura M. et al.Observation of deworming process in intestinal Diphyllobothrium latum parasitism by gastrografin injection into jejunum through double-balloon enteroscope.Am J Gastroenterol. 2008; 103: 2149-2150Crossref PubMed Scopus (6) Google Scholar When the Gastrografin passed rapidly through the small intestine, the worm was carried away from the jejunum toward the colon by intestinal peristalsis (Figure E). In the discharge, an actively moving worm, measuring approximately 200 cm in length with an intact scolex (circle) and neck, was noted (Figure F). The whole course of the tapeworm discharge was observed radiologically, which took only a short time (35 minutes). There was no evidence of relapse during the next 9 months. Treatments with anthelmintics occasionally have toxic effects on the host, require the specific preparation of the patient before treatment, and cause the death of the tapeworm. However, the Gastrografin method can attack the tapeworm in its active form and remove it with an intact scolex. It is important to remove the scolex to avoid a recurrence of infection. Gastrografin injection is therefore considered to be easy to perform as well as a safe and effective treatment in comparison to the use of anthelmintics.

Superficial Bladder Tumors In Childhood

PURPOSE To present the clinical, histological features and the prognosis of superficial bladder tumors (SBT) in childhood. MATERIAL AND METHODS A total of 6 male children, 4-14 yrs old (mean age 11yrs.), treated at our Department between 1984 and 2006, were found to have SBT. Presenting symptoms included gross heamaturia in 5, irritative voiding and microscopic heamaturia in 1. Initial diagnosis was made by ultrasound. Cystoscopy confirmed the diagnosis and 5 patients underwent transurethral resection of the tumor which was solitary. The remaining patient underwent transvesical excision due to the presence of two exophytic lesions measuring 3,2 and 2,5 cm in diameter respectively. Follow up consisted of ultrasound which was performed every 3 months in the first year and every 6 months later. RESULTS Pathologic evaluation revealed low grade pTa transitional cell carcinoma (TCC) in 5 cases and nephrogenic adenoma (NA) in 1. The case with NA had been operated on obstructive megaureter in early infancy.During follow up (2-24 years), there was no evidence of relapse. CONCLUSIONS Despite the fact that S.B.T. are rare in childhood, all children presented with gross heamaturia must be investigated. Bladder ultrasound is the most sensitive scan in exophytic lesions > 3mm. The appropriate treatment option is transurethral resection of the tumor which mostly is solitary. During follow up there was no evidence of relapse.

Partial Breast Brachytherapy as the Primary Treatment for Breast Cancer Diagnosed After Mantle Radiation Therapy for Hodgkin's Disease

Mastectomy is the most widely accepted treatment for managing breast cancer in patients who have previously received mantle radiation therapy (RT). With accumulating evidence supporting partial breast irradiation, we treated newly diagnosed breast cancer among lymphoma survivors who had history of RT with lumpectomy and breast brachytherapy. Five patients, with history of Hodgkin disease (HD) underwent lumpectomy and sentinel lymphadenectomy +/- axillary dissection followed by low dose rate Ir-192 interstitial brachytherapy. A multicatheter technique was used and all patients received 45 Gy to the target volume over 4 to 5 day time interval. Adjuvant systemic therapy when indicated was administered after completion of brachytherapy. The median time from the treatment of the HD to the diagnosis of breast cancer was 242 months (range: 68-322 months). The median T-size of the invasive breast cancer is 0.7 cm. The range of follow up after brachytherapy is 5 to 67 months. All 5 patients have an intact breast and are without evidence of relapse. No patients developed an infection. No skin toxicity > or =grade 2 was observed. All patients have an excellent cosmetic result. No excessive fibrosis or necrosis has been observed. The preliminary experience using partial breast brachytherapy (PBB) in patients with previous history of mantle RT suggests low complication rates, and acceptable cosmetic results. The excellent local control and freedom from mastectomy for local recurrence warrants further investigation to establish brachytherapy as an acceptable alternative to mastectomy for early stage breast cancer among HD survivors with history of prior RT.

Scedosporium apiospermumskeletal infection in an immunocompetent child

Abstract This is a case of Scedosporium apiospermum skeletal infection in a 10-year-old immunocompetent girl whose chief complaint was left knee swelling and pain. The child had a history of a bicycle accident two months before with a resultant deep penetrating trauma. Systematic administration of broad-spectrum antibiotics for 10 days was used, with no clinical improvement. Magnetic Resonance Imaging and arthrotomy of the affected joint revealed findings suggestive of osteomyelitis. Empirical intravenous antimicrobial therapy was instituted for a total of two months but one month after completion of antibacterial therapy the child returned to the hospital because of persistent knee swelling and pain. Following a new arthrotomy, Scedosporium apiospermum was isolated. The patient was cured with intravenous administration of voriconazole without any side effects and has no evidence of relapse after four years of follow-up.

Does the Occurrence of Invasive Fungal Infection in Acute Leukemia Patients, Impact on the Chemotherapy Schedule and Event-Free Survival? a Case-Control Study

Background: In acute leukemia (AL) patients, mortality rates of the most common IFI (i.e., aspergillosis and candidiasis) are well illustrated in the literature from the IFI diagnosis, as well as the rate of fungal relapse during subsequent periods at risk, such as neutropenic phases, or transplant. However, few data are available about the impact of IFI on the subsequent chemotherapy schedule and the indirect impact of IFI on the relapse-free and overall survival. Clinicians are usually reluctant to give the full chemotherapy doses on time, due to the risk of life-threatening fungal relapse during the subsequent courses. Even with secondary prophylaxis, they often delay or decrease the doses of chemotherapy. This may impact on the leukemia outcome. The aim of this case-control study was to assess the potential impact of proven or probable IFI onset on the application of the chemotherapy schedule in AL patients, and its consequences on the leukemia outcome, by comparing patients with and without IFI in a single institution. Delays and changes in chemotherapy doses and drug choices were evaluated and compared to the planned schedule in the protocol.Methods: All consecutive AL patients with a first episode of proven or probable IFI according to the EORTC-MSG criteria between 2000–2006 were reviewed. All patients have been treated in, or according to, clinical research protocols where timing and doses of chemotherapy were predefined. Patients who were planned for allogeneic transplant were excluded as those who were at their last consolidation course when they got IFI or in a palliative phase of the leukemia. Any delay, dose decrease, or dose change were defined as any difference compared to the planned schedule. We planned to include 3 control patients for each case, selected among AL patients without IFI, and matched for age, sex, type of AL, chemotherapy protocol, and year of treatment. 27 case and 76 control patients were finally included. The event-free survival (EFS) was defined as survival without evidence of relapse or progression, or death of any cause.Results: The mean age of the 27 case patients (26 myeloid and 1 lymphoblastic AL) was 52 y (± 13), the M/F ratio was 14/13 IFI (7 candidiasis, 19 aspergillosis, 1 zygomycosis) was proven for 10 patients (37%), and probable for 17 (63%). Twenty (71%) of these IFI occurred during the first induction phase. All patients were treated for their IFI with ≥ 1 antifungal, and 4 of them had a surgical resection of the main fungal lesion(s). These 27 patients were compared to 76 controls (73 myeloid and 3 lymphoblastic AL) without IFI. A delay of the next course of chemotherapy according to the planned protocol was significantly more frequent in the IFI group (16/27, 59%) than in the control group (16/76, 21%) (p=.001). Similarly, the dose or choice of the drugs was modified more frequently in the IFI group (7/27, 26%) than in the control group (6/76, 8%) (p=.037). Only 9 (33%) patients got their next chemotherapy course without any modification in time, dose, or choice of drug, vs. 19/76 (75%) in the control group (p<.0001). The EFS of the IFI group was lower than that of the control group, although this difference was not significant.Conclusion: In this single-institution case-control study, the occurrence of IFI significantly modified the application of chemotherapy courses, both on timing of the courses, and dose and choice of the drugs when compared to patients without IFI. Although the difference was not significant, there was a tendency for a lower EFS in the IFI group when compared to the control group.−

Donor Lymphocyte Infusions (DLI) for the Treatment of Disease Relapse in Hematological Malignancies Following Allogeneic Transplantation: Similar Efficacy Following RIC or Myeloablative Regimen

DLI have been shown to have a potent GVL effect in relapsing chronic phase CML while for reasons that remain unclear, they appear less effective in treating relapsing diseases other than CML. A lack of tumor-specific antigens, the absence of co-stimulatory molecules on tumor cells, or inhibition of effector cells may account for the lower therapeutic effect. Given the sub-optimal results of DLI in non-CML diseases, predictive factors of DLI efficacy such as type and stage of the disease and levels of chimerism would serve to better guide the use of leukocytes infusions.We analyzed a series of 73 patients (pts) who received DLI for various indications (disease relapse or progression, n=66; persistent mixed chimerism (less than 90% donor cells) without evidence of relapse, n=4; EBV lymphoproliferation, n=3). Diagnosis included: CML (n=9), MDS or AML (n=21), LAL (n=5), myeloma (n=18), NHL (n=10), Hodgkin's disease (n=5), CLL (n=2), and other (n=3). Median age at transplantation was 46 (1–62) years. Eigthy-six percent of donors were HLA-matched siblings, while 12% were MUD, one donor was a haplo-identical sibling, and two had one class I mismatch. Reduced intensity conditioning was used in 39 patients (52%; fludarabine, busulfan and ATG), and 35 pts (48%) received a standard myeloablative TBI/cyclophosphamide-based regimen. The graft was T-cell depleted in 14 cases. GHVD prophylaxis consisted of CsA alone in RIC patients, and CsA+Mtx in the myeloablative group. DLI was given at a median of 247 (19–3163) days after transplantation. Escalating dose were given if no response or GVHD were observed: one DLI n=36, 2 infusions (n=36), 3 infusions (n=5), 4 infusions (n=1). The median pre-DLI lymphocyte count was 0.95×109/L (0.05–4.38). In addition to DLI, 22 pts (47%) received prior (n=9, 19%) or subsequent chemotherapy to enhance disease control. In those who received DLI for mixed chimerism alone, all four returned to full donor chimerism. In those who received DLI for relapsing/progressive disease, CR was achieved in 21 pts (28%), including 15 with non-CML diseases (23%): 6/21 AML, 5/18 MM, 2/10 NHL, 1/5 HD, 1/5 ALL. In 16 pts, CR was obtained with DLI only. Two of the three patients who received DLI for EBV lymphoproliferation responded. Response to DLI was comparable between pts receiving RIC regimen and myeloablative regimen (p=ns). The rate of acute GVHD II-IV and chronic GVHD was 27% and 23%. The incidence of acute GVHD II-IV did not differ whether the conditioning was myeloablative or RIC while the rate of GVHD was higher in recipient of DLI from unrelated donor (60%, although the number is small). Chimerism was performed on unselected WBC and available prior DLI for 7/9 of CML pts, and 54/65 non-CML pts. For non-CML disease donor chimerism was <90% for 17 pts (including 6 pts with <50%) and ≥90% for 37 pts with an incidence of acute grade II-III GVHD of 52% and 32% respectively (p=ns). Correlation was observed between GVHD and graft versus malignancy in non-CML diseases (.015). The median overall survival was 28.3 months. The overall probability of survival following DLI at 2 and 4 years was 50.7% and 40.5% (95% CI, 27.7–53.3) for the whole group; the survival at 4 years according to the disease was 38.8% for AML/MDS, 40% for NHL, 35.7% for myeloma. With a median follow-up of 1662 days from the time of the initial DLI, 33/73 pts of the whole group (45%) are alive, while in the non CML group 26/64 (37.5%) pts are alive and 18/64 (28%) alive in CR. These results indicate that DLI combined with chemotherapy for disease relapse or mixed chimerism is similarly effective in non-CML diseases following RIC or standard allografting and works in one case out of four in AML and myeloma. Its efficacy can be further improved with the use of more tumor-specific DLI and reduction of the suppressing activity of regulatory T cells.

Autologous Hematopoietic Stem Cell Transplantation (HSCT) for Autoimmune Diseases: 10 Years Experience from the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Autoimmune Diseases

Introduction Since 1996 a joint collaborative effort from the European Group for Blood and Marrow Transplantation (EBMT) and League against Rheumatism (EULAR) collected cases of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for patients (pts) with severe autoimmune diseases (AD). This retrospective observational study was designed to assess patients outcome and analyse the determinants of treatment responses after AHSCT.Methods All consecutive AD pts treated by AHSCT from 1996 to 2007 according to the EBMT-EULAR consensus statement with ethics committee approved protocol were included. Data were reported yearly via the electronic EBMT data management system PROMISE and outcomes updated as December 2007. Standard AHSCT techniques used either bone marrow (BM), peripheral blood stem cells (PBSC) or both. PBSC were collected with cyclophosphamide CY (CY 4 g/m2) + granulocyte-colony stimulating factor (G-CSF), or with G-CSF alone if cardiac function prevented CY.Cell selection used either CD34+ selection with or without monoclonal antibodies, particularly anti-CD52, anti-CD3, anti- CD19 or anti-CD20. Conditioning regimen used either Total Body Irradiation (TBI) or chemotherapy alone, with various combinations of CY, Busulfan, BEAM ± Antithymocyte Globulins (ATG), which were then subgrouped arbitrarily intohigh intensity regimen, including Busulfan or TBI,low intensity restricted to CY alone, Melphalan alone and Fludarabine-based regimens, orintermediate regimen with all the other combinations.Primary outcome measure was Progression Free Survival (PFS) defined as survival without evidence of relapse or progression. Secondary outcomes were the Overall Survival (OS) defined as time to death, irrespective of the cause and Transplant Related Mortality (TRM) at day 100, defined as death without ADs relapse or progression. Cumulative incidence curves were used for TRM, considering relapse or progression within 100 days as a competing event and compared using the Gray's test. Kaplan-Meier estimate was used to calculate PFS Probabilities and the log-rank test for univariate comparisons. For all pronostic analyses, continuous variables were categorised and the median was used as a cut-off point. Associations of patient, disease and graft characteristics with outcomes were evaluated in multivariate analyses, using Cox proportional hazards for PFS, and proportional hazard regression model of Fine and Gray for NRM. Results: From 1996 to December 2007, 900 AD pts (64 % female, median 35 years) from 171 teams in 27 countries treated by AHSCT were reported to the EBMT data base, mainly multiple sclerosis (MS, n=345), systemic sclerosis (SSc, n=175), systemic lupus erythematosus (SLE, n=85), rheumatoid arthritis (RA, n=89), juvenile idiopathic arthritis (JIA, n=65), vasculitis (VASC, n=26) and hematological immune cytopenia (HIC, n=37). PSC were used as stem cell source for 92% of the pts; 42 % of the pts had in vitro cell selection, mostly with CD34+ selection. All types of conditioning regimens were used in all disease categories with very few patients (7%) with TBI. On the overall population, the 5 years PFS was 43 ± 2 % and OS was 85 ± 1 %. Three years after AHSCT:PFS was 61±5 % for SSc, 55±3 % for MS, 54±6 % for SLE, 52±7 % for JIA, 53±15 % for PMDM, 47±11 % for VASC, 34±9 % for HIC and 23±5 % for RA,);OS was 98 ± 2 % for RA, 93 ± 2 % for MS, 82 ± 5 % for JIA, 83 ± 5 % for SLE and 77 ± 4 % for SSc, depending primarily on AD type (p<0.001).By multivariate analysis, the age > 35 yrs (HR 0.73, 95%CI (0.59–0.89), p=0.002), AHSCT performed before December 2000 (HR 0.69, 95%CI (0.55–0.85), p=0.008) and number of AHSCT for ADs per centre £ 13 (HR 0.82, 95%CI (0.67–0.99, p=0.05) were associated with a lower PFS. The day 100 TRM was 5 ± 1% overall and appeared significantly lower for a number of patients per centre > 13 (HR 0.45, 95% CI (0.21–0.99), p=0.05).ConclusionThe EBMT registry allowed to collect 900 ADs pts with AHSCT after 10 years of collaborative effort. Although retrospective, this largest cohort studied worldwide so far showed that patient age, AD type and number of AHSCT per centre are important determinants of the response. AHSCT appeared a good therapeutic alternative for severe Ads unresponsive to conventional treatment, supporting the ongoing European and north American phase 3 trials comparing AHSCT to standard therapies in SSc, MS, SLE and Crohn's disease.

Detection of Pre-Transplant Clonal Cytogenetic Abnormalities in Stem Cells Used for Autologous Stem Cell Transplant in Relapsed Non-Hodgkin Lymphoma Is a Predictor of Relapse

Autologous stem cell transplant is used for chemotherapy sensitive relapsed Non-Hodgkin Lymphoma (NHL). Patients who receive an autologous stem cell transplant after high dose chemotherapy for relapsed NHL have significantly superior survival compared to those receiving conventional chemotherapy. Relapsed patients who achieve a second remission are treated with myeloablative chemotherapy followed by autologous stem cell transplant. These patients can achieve 5-year event free survival close to 50% and 5-year overall survival of greater than 50%. We performed a retrospective analysis of our center's transplant data and reviewed pre-transplant cytogenetic analysis on the patient's collected stem cells. 259 patients underwent autologous stem cell transplant from 1998 through 2007 for relapsed NHL. Cytogenetic evaluations of the patient's pre-transplant stem cells had been done to look for evidence of MDS or characteristics of their lymphoma. Clonal cytogenetic abnormalities were found in 12 of the 259 patients. Two of these patients died within 45 days of transplant without evidence of relapse. One from infection and a second from non-treatment related causes. Nine of the remaining 11 (81%) patients with clonal cytogenetic abnormalities have relapsed and died. All patients relapsed with their original lymphoma. The cytogenetic abnormalities were varied. Out of the 9 relapses, 3 had cytogenetic abnormalities in the stem cells that are associated with lymphoma, 2 that are associated with AML, 1 that is associated with MDS, and 2 were abnormalities whose significance was unknown. In one patient cytogenetic changes of the original lymphoma were identified. The patients that had clonal cytogenetic abnormalities in their collected stem cells had an 81% relapse rate as opposed to 30% in the patients whose stem cells had a normal karyotype. Our findings show that cytogenetic changes in the collected stem cells are associated with a higher rate of lymphoma relapse.

A patient with funny spells

A 42 year old nurse presented to her general practitioner with a five year history of intermittent episodes of dizziness, palpitations, and sharp central chest pain. There was no radiation or aggravating or alleviating factors. She complained that the colour of her hands and feet would drain to white, and they would feel cold. Her pulse would become impalpable, progressing to a weak irregular rhythm before returning to normal. All symptoms started at the same time, each episode lasting up to a minute before resolving simultaneously. They were not associated with exercise or posture, and her general condition improved quickly after each episode. She had no associated symptoms of breathlessness, syncope, or fits. She was diagnosed as having chronic myeloid leukaemia at 32 and treated with bone marrow transplant and irradiation, with no evidence of relapse. She had never smoked and rarely drank alcohol. On examination, her blood pressure was 110/80 mm Hg, with postural hypotension, and her pulse was 80 beats/min, with normal sinus arrhythmia. …

Study to Determine Adequate Margins in Radiotherapy Planning for Esophageal Carcinoma by Detailing Patterns of Recurrence After Definitive Chemoradiotherapy

To ascertain the adequacy of radiotherapy (RT) margins by studying the relapse patterns after definitive chemoradiotherapy for carcinoma of the esophagus. We performed a retrospective study assessing the first site of disease relapse after definitive chemoradiotherapy that included four 3-weekly cycles of cisplatin and continuous infusion 5-fluorouracil, with conformal RT (50 Gy in 25 fractions) concurrent with Cycles 3 and 4. The RT planning target volume was the endoscopic ultrasonography/computed tomography-defined gross tumor volume with 1.5-cm lateral and 3-cm superoinferior margins. A total of 145 patients were included. Their average age was 65.4 years, 45% had adenocarcinoma, 61% had lower third esophageal tumors, and 75% had Stage III-IVA disease. After RT, of 142 patients, 85 (60%) had evidence of relapse at a median follow-up of 18 months. The relapse was local (within the RT field) in 55; distant (metastatic) in 13, and a combination of local and distant in 14. The local relapse rates were not influenced by tumor stage, lymph node status, or disease length. Three patients developed a relapse in regions adjacent to the RT fields; however, it is unlikely that larger field margins would have been clinically acceptable or effective in these cases. The median overall survival was 15 months. The gross tumor volume-planning target volume margins in this study appeared adequate. Future efforts to improve outcomes using definitive chemoradiotherapy should be directed toward reducing the high rates of in-field and distant relapses.

A Pharmacodynamic Model for the Time Course of Tumor Shrinkage by Gemcitabine + Carboplatin in Non–Small Cell Lung Cancer Patients

This tumor response pharmacodynamic model aims to describe primary lesion shrinkage in non-small cell lung cancer over time and determine if concentration-based exposure metrics for gemcitabine or that of its metabolites, 2',2'-difluorodeoxyuridine or gemcitabine triphosphate, are better than gemcitabine dose for prediction of individual response. Gemcitabine was given thrice weekly on days 1 and 8 in combination with carboplatin, which was given only on day 1 of every cycle. Gemcitabine amount in the body and area under the concentration-time curves of plasma gemcitabine, 2',2'-difluorodeoxyuridine, and intracellular gemcitabine triphosphate in white cells were compared to determine which best describes tumor shrinkage over time. Tumor growth kinetics were described using a Gompertz-like model. The apparent half-life for the effect of gemcitabine was 7.67 weeks. The tumor turnover time constant was 21.8 week.cm. Baseline tumor size and gemcitabine amount in the body to attain 50% of tumor shrinkage were estimated to be 6.66 cm and 10,600 mg. There was no evidence of relapse during treatment. Concentration-based exposure metrics for gemcitabine and its metabolites were no better than gemcitabine amount in predicting tumor shrinkage in primary lung cancer lesions. Gemcitabine dose-based models did marginally better than treatment-based models that ignored doses of drug administered to patients. Modeling tumor shrinkage in primary lesions can be used to quantify individual sensitivity and response to antitumor effects of anticancer drugs.

Diagnosis and treatment of hepatocellular adenoma

Objective To study the clinicopathological characteristics, the procedure of diagnosis and treatment and prognosis of hepatocellular adenoma. Methods The clinicopathological data and prognoses of 11 cases of hepatocellular adenoma treated in our hospital from January 1 989 to March 2006 were retrospectively analyzed. Results There was no specific symptom among the patients. The average diameter of the tumors was 6.27 cm. Loeal excision was performed in 6 cases. Segmental excision of the liver was performed in 3 patients. Two patients underwent left hepatectomy after TACE. All patients were followed up for 5-232 months and the average survival time was 53.5 months. No evidence of relapse and metastasis in these patients was found. Conclusion Hepatocellular adenoma is a rare kind of benign tumor of the liver and surgical resection is the effective way to cure it. The choice of surgical procedures depends on the location and size of the tumor. Complete resection results in good prognosis. Key words: Liver neoplasms; Diagnosis; Treatment; Prognosis