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J Yahalom

Publications and source records attributed to J Yahalom.

At least 19 recordsLinked to original sources
PubMed2006

Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials.

BACKGROUND: Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial. PATIENTS AND METHODS: We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method. RESULTS: Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25). CONCLUSIONS: Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.

Combined Modality Therapy↗
PubMed2005

FDG-PET scanning for detection and staging of extranodal marginal zone lymphomas of the MALT type: a report of 42 cases.

BACKGROUND: Although reports have suggested that FDG-PET scans were not useful for staging of extranodal marginal zone lymphomas (MZL), experience at our center suggests otherwise. Thus we reviewed the findings of FDG-PET scans in patients with extranodal MZL seen at our center. PATIENTS AND METHODS: A database of 175 patients with histologically-confirmed diagnoses of extranodal MZL was reviewed. Forty-two patients who had had FDG-PET scans for initial staging were identified. All information was obtained by retrospective review of medical records and PET scans. RESULTS: Thirty-four (81%) patients had focal tracer uptake within verified tumor sites, six (14%) patients did not, and two (5%) patients had indeterminate uptake. Seven of the 34 (21%) patients with uptake within verified tumor sites had uptake in regional lymph nodes and four patients were upstaged due to FDG-PET findings. Eight patients also obtained post-treatment FDG-PET scans. In five of those eight, the repeated FDG-PET scan indicated a complete response, and in three there was an indeterminate or mixed response. CONCLUSION: FDG-PET scans carried out for initial staging of extranodal MZL detected disease in a high proportion of patients. This study suggests that imaging with FDG-PET scans is useful for both initial staging and follow-up of patients with extranodal MZL.

Adult↗
PubMed2004

The NHL-15 protocol for aggressive non-Hodgkin's lymphomas: a sequential dose-dense, dose-intense regimen of doxorubicin, vincristine and high-dose cyclophosphamide.

BACKGROUND: The NHL-15 protocol is a novel, dose-intense, dose-dense, sequential chemotherapy program developed to improve outcome in advanced, aggressive non-Hodgkin's lymphomas. PATIENTS AND METHODS: The phase II NHL-15 protocol comprised: (i) induction [doxorubicin 60 mg/m(2) i.v. on weeks 1, 3, 5 and 7 plus vincristine 1.4 mg/m(2) i.v. (no cap) on weeks 1, 2, 3, 5 and 7]; and (ii) consolidation (cyclophosphamide 3000 mg/m(2) i.v. on weeks 9, 11 and 13 plus granulocyte colony-stimulating factor 5 microg/kg subcutaneous on days 3-10 following each cyclophosphamide dose). Patients with aggressive non-Hodgkin's lymphomas (working formulation: intermediate grade or immunoblastic), bulky stage I and stages II-IV, were eligible. RESULTS: There are 165 eligible patients with a 6.9-year median follow-up (range 0.5-141 months) and a median age of 48 years. For the entire group, 72.1% achieved complete remission, and at 5 years disease-free survival was 57.8% and overall survival (OS) was 62.2%. Ideal dose delivery was >90%. Acute and late toxicities of treatment were manageable and acceptable. Toxic death on treatment was 2.4%. When the diffuse large cell lymphoma histologies were grouped according to the International Prognostic Index (IPI), complete remission and OS in the low-intermediate (LI), and high-intermediate (HI) risk groups were improved by 5%-15% compared with historical CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). This improvement was also noted for LI and HI risk groups in the age-adjusted (aa)IPI analysis for patients < or =60 years of age. CONCLUSIONS: The NHL-15 program can be administered safely and effectively to achieve high rates of durable remission when used for the treatment of advanced stage, aggressive, non-Hodgkin's lymphomas. The 5%-15% improvement in 5-year OS compared with historical CHOP, according to the IPI/aaIPI model (in LI and HI risk groups), is encouraging. Further evaluation and prospective testing of the NHL-15 protocol appears to be warranted.

Adolescent↗
PubMed2003

Progressive disease following autologous transplantation in patients with chemosensitive relapsed or primary refractory Hodgkin's disease or aggressive non-Hodgkin's lymphoma.

To determine the outcome of patients with chemosensitive relapsed or primary refractory Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL) whose disease progresses after autologous stem cell transplantation (ASCT), we reviewed the records of 82 patients with HD and 139 patients with NHL transplanted between 1993 and 2000. Disease progression occurred in 25 patients with HD and 66 patients with NHL, with median times to progression (TTP) of 3.8 and 5.1 months, respectively. Median survival times following ASCT failure were 26 and 7.7 months for patients with HD and NHL, respectively. The second-line international prognostic index (sIPI) and the TTP (before or after 3 months from ASCT) independently were predictive of survival for NHL patients. In addition, treatment with rituximab for patients with B cell NHL was associated with improved survival (median 28.6 vs 4.1 months, P=0.003), independent of the sIPI and TTP. Prognostic factors for patients with HD were not identified. Only two patients, one of whom was among six patients who received second autologous transplants, remain disease-free. The uniformly poor outcome associated with disease progression after ASCT should prompt efforts to assess the feasibility and utility of detecting and treating post transplant residual disease during a minimal disease state, before overt progression.

Adolescent↗
PubMed2003

Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma.

Despite advances in the management of aggressive non-Hodgkin's lymphoma, the treatment of relapsed and primary refractory disease remains a major challenge. High-dose chemotherapy or radio-chemotherapy followed by autologous or allogeneic stem cell transplantation (SCT) is a potentially curative treatment approach; however, the applicability of this approach is restricted to patients responding to second-line chemotherapy. Thus, second-line therapy must be both efficacious and without stem cell or organ toxicity that would compromise the ability to proceed to SCT. The ifosfamide, carboplatin and etoposide (ICE) regimen was developed to address these challenges. In a series of prospective clinical trials, 222 patients were treated with the ICE regimen. with an overall response rate of 72%. The mobilization of stem cells with this regimen was excellent,with 86% of patients mobilizing at least 2.0 x 10(6) CD34+ cells/kg. The incidence of treatment-related toxicity precluding SCT after ICE is very low. Herein, we report the clinical results of this treatment program for 222 patients with 5-year median follow-up for surviving patients. Rituximab was subsequently added to the ICE regimen for patients with diffuse large B-cell lymphoma (DLBCL) to improve upon these favorable results. This resulted in an increased complete remission rate. Additional follow-up is necessary to determine if this improvement in the complete remission rate will confer an increase in the overall survival following SCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

The involved field is back: issues in delineating the radiation field in Hodgkin's disease.

During the last century, the role of radiation therapy in the treatment of Hodgkin's disease (HD) has changed drastically. From a palliative treatment reserved for bulky lymph nodes of an incurable disease at the beginning of the century, to an exciting primary treatment used alone to cure most stages in the 1960s and 1970s, to the present more limited role as consolidation treatment after chemotherapy. Interestingly, the radiation field size has always influenced the evolution of treatment principles of HD. Over several decades, large or extended field radiotherapy has become synonymous with the successful treatment of HD. But the critical transformation from a single-modality to a combined-modality therapy, together with improvement in imaging and radiation planning techniques, mandates a reassessment of the delineation of appropriate radiation fields in HD. In this manuscript we review the comeback of the involved field, address design questions and offer field borders for common disease sites.

Clinical Trials as Topic↗
PubMed2001

A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model.

Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P <.001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT.

Adolescent↗
PubMed2001

A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles.

The mechanisms underlying neoplastic epithelial cell killing by ionizing radiation are largely unknown. We discovered a novel response to radiation manifested by autophagy and the development of acidic vesicular organelles (AVO). Acidification of AVO was mediated by the vacuolar H+-ATPase. Staining with the lysosomotropic agent acridine orange enabled us to quantify AVO accumulation and to demonstrate their time- and dose-dependent appearance. The appearance of AVO occurred in the presence of the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethyl ketone, but was inhibited by 3-methyladenine, an inhibitor of autophagy. The accretion of AVO in surviving progenies of irradiated cells, and the increased incidence of clonogenic death after inhibition of vacuolar H+-ATPase suggest that formation of acidic organelles represents a novel defense mechanism against radiation damage.

Adenine↗
PubMed2001

Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor.

Recent studies from our laboratory have revealed that basic fibroblast growth factor (bFGF) selectively inhibits the proliferation of human MCF-7 breast cancer cells. It has also been shown to enhance cis-platinum-induced apoptosis, decrease levels of the anti-apoptotic gene product bcl-2, and increase levels of the cyclin-dependent protein kinase inhibitor p21/WAF1/Cip1. Transforming growth factor beta-1 (TGFbeta1), a cell growth regulator has been found to have an inhibitory effect on breast cancer cells. The aim of the present study was to evaluate the possible role of TGFbeta1 in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGFbeta1 mRNA expression in the cells and enhanced the secretion of TGFbeta1 into culture medium. However, exogenous addition of TGFbeta1 neither led to a decrease in bcl-2 nor induced an increase in the levels of p21/WAF1/Cip1 and neutralizing antibodies to TGFbeta1, did not reverse bFGF-induced G1 arrest northe increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGFbeta1 abrogated the antiproliferative effects and inhibited the induction of p21/WAF1/Cip1 by bFGF in MCF-7 cells. These data suggest that the anti-proliferative effects of bFGF in human MCF-7 breast cancer cells are mediated by endogenous TGFbeta1, while exogenous TGFbeta1 does not mimic all the effects of bFGF on these breast cancer cells. These findings provide an important basis for further investigations into the autocrine and paracrine processes that control the growth of breast cancer cells.

Angiogenesis Inhibitors↗
PubMed2000

High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis.

High-dose chemoradiotherapy (HDT) with autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, its role in the treatment of patients with primary refractory disease is not well defined. The outcomes of 85 patients with primary refractory aggressive NHL who underwent second-line chemotherapy with ICE with the intent of administering HDT/ASCT to those patients with chemosensitive disease were reviewed. Patients were retrospectively classified as induction partial responders (IPR) if they attained a partial response to doxorubicin-based front-line therapy or as induction failures (IF) if they had less than partial response. Forty-three patients (50.6%) had ICE-chemosensitive disease; there was no difference in the response rate between the IPR and the IF groups. Intention-to-treat analysis revealed that 25% of the patients were alive and 21.9% were event-free at a median follow-up of 35 months. Among 42 patients who underwent transplantation, the 3-year overall and event-free survival rates were 52.5% and 44.2%, respectively, similar to the outcomes for patients with chemosensitive relapsed disease. No differences were observed between the IPR and IF groups, and there were no transplantation-related deaths. More than one extranodal site of disease and a second-line age-adjusted International Prognostic Index of 3 or 4 before ICE chemotherapy were predictive of poor survival. These results suggest that patients with primary refractory aggressive NHL should receive second-line chemotherapy, with the intent of administering HDT/ASCT to those with chemosensitive disease. Newer therapies are needed to improve the outcomes of patients with poor-risk primary refractory disease.

Adult↗
PubMed2000

Low-grade MALT lymphoma of the stomach: a review of treatment options.

PURPOSE: Low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach (MLS) is often associated with the presence of Helicobacter pylori (H. pylori) bacteria. Eradication of the infection with antibiotic therapy may result in regression of the lymphoma. But when antibiotic treatment fails to reverse the malignant process or if H. pylori is absent, other treatment options should be considered. Because MLS is often confined to the stomach and regional lymph nodes, it is potentially curable with local therapy. Endoscopy and improved imaging, with endoscopic ultrasound (EUS) and computerized tomography (CT), have reduced the prior dependence on surgery for diagnosis and staging of gastric lymphomas. METHODS AND RESULTS: This review details the advances in the diagnosis, classification, and imaging of MLS. We also describe the experience that supports the use of radiation therapy as the preferred treatment of MLS in patients who have not responded to antibiotic therapy or have not had evidence for H. pylori infection. CONCLUSIONS: Radiation therapy for MLS is not only effective and safe, but offers the significant advantage of low morbidity and gastric function preservation.

Anti-Bacterial Agents↗
PubMed2000

Optimal matchline blocking and matchline dosimetry for lymphoma patients.

Patient setup and geometrical factors can potentially lead to excessive spinal cord doses when treating lymphoma patients with matched mantle and para-aortic (PAN) fields. To ensure cord protection, partial transmission blocks are often used at the matchline. This study evaluates optimal placement of these blocks. Three patients were planned using a variety of mantle/PAN field geometries, including significantly different field lengths and isocenter vertical positions. Field matching in all cases was based on a standard gap calculation. Half-transmission blocks (HTB) were positioned on (a) both posterior fields, (b) both anterior fields, and (c) the posterior PAN field only. Doses were calculated with and without effects of setup uncertainty. HTB on both posterior fields yielded a lower maximum cord dose but slightly poorer target coverage than HTB on both anterior fields. HTB on the posterior PAN field alone resulted in a maximum cord dose similar to HTB on both anterior fields. Setup uncertainty decreased but did not eliminate the differences between block placement methods. HTB of sufficient size on both posterior fields ensures a maximum cord dose less than the prescription without significant compromise of target coverage.

Humans↗
PubMed2000

Treatment for primary CNS lymphoma: the next step.

PURPOSE: The use of preradiotherapy (RT) methotrexate (MTX) has improved disease control and survival in patients with primary CNS lymphoma (PCNSL). The reported protocol was designed to optimize and enhance the chemotherapeutic component of treatment. PATIENTS AND METHODS: Fifty-two patients were treated with five cycles of high-dose MTX 3.5 g/m(2), procarbazine 100 mg/m(2)/d, and vincristine 1.4 mg/m(2). Thirty patients received whole-brain RT (45 Gy). Twenty-two older patients deferred RT to diminish the risk of delayed neurotoxicity; these patients are compared with 12 older patients who completed the entire treatment regimen. Most patients (n = 35) received high-dose cytarabine after RT. RESULTS: Objective response rate to the induction chemotherapy regimen was 90%; overall median survival is 60 months. Grade 3 or 4 myelosuppression was seen in 30 patients, primarily in association with cytarabine; grade 3 nephrotoxicity due to MTX was seen in two patients. Older patients had similar median survival with or without the addition of RT: 32 versus 33 months, respectively. However, late neurotoxicity was significantly more common in those older patients who received RT (P: =.00004). Patients younger than 60 years who received the complete treatment regimen have not reached median disease-free or overall survival. CONCLUSION: Increasing the dose of MTX and adding procarbazine and vincristine improved disease control and overall survival in patients with newly diagnosed PCNSL. Younger patients in particular fared extremely well with this treatment regimen. In older patients, deferring whole-brain RT did not compromise overall survival but did reduce treatment-related toxicity.

Adult↗
PubMed2000

Radiotherapy in the management of plasma cell tumors.

Most patients with plasma cell tumors receive radiation therapy at some time during the course of their disease. Plasma cell tumors are radio-responsive, but the systemic nature of the disease in most patients limits the application of localized irradiation. In patients with solitary plasmacytomas (osseous and non-osseous), radiation therapy is the primary treatment modality. It provides excellent local control that may translate into a long remission and even cure. Adequate dose and careful anatomic planning are essential. In patients with multiple myeloma, effective palliation of pain can be achieved with relatively small fields and low doses of radiation. Hemibody irradiation has been shown to provide cost-effective palliation but is associated with toxicity and has failed to contribute to a more definitive therapeutic approach. Hemibody irradiation is rarely used today. Total-body irradiation is often employed in conditioning regimens prior to autologous or allogeneic stem-cell transplantation for multiple myeloma. However, the magnitude of its contribution to the efficacy of high-dose programs in multiple myeloma remains to be studied. This article explores the rationale for and various aspects of providing effective radiotherapy in patients with plasma cell tumors.

Humans↗