Summary:Genetic aberrations have emerged as major prognostic factors for patients with multiple myeloma (MM). We evaluated 126 MM patients for t(4;14) or t(11;14), 13q or p53 deletions and correlated the number of genetic aberrations with patient's clinical outcome following undergoing autologous stem cell transplantation. We demonstrate the significance of genetic-based risk classification that clearly segregate patients into low (no genetic abnormalities or only t(11;14)), intermediate (any one of the genetic abnormalities other than t(11;14)) and highrisk groups (any two or more of the genetic abnormalities other than t(11;14)). High-risk patients do not benefit from stem cell transplant and should be offered alternative therapies. deletions; p53 deletions; fluorescence in situ hybridization; autologous stem cell transplantation Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by recurrent genetic changes that include chromosome 13q14 deletions and translocations involving the immunoglobulin heavy chain switch region (IgH) with various partner genes, most commonly t(11;14) and t(4;14).1,2 We and others have found that t(4;14) but not t(11;14) detected by cytoplasmic fluorescence in situ hybridization (cIg-FISH), is an adverse risk factor for MM patients receiving high-dose therapy and autologous stem cell transplantation (ASCT). 3,4 In addition, we found that p53 deletions are an independent adverse prognostic factor in MM patients undergoing ASCT. 5 We now extend our analysis by studying MM patients evaluated by cIg-FISH for each of these four genetic abnormalities and propose a new genetic-based risk stratification model for MM patients treated with high-dose chemotherapy and ASCT. Specifically, we suggest that genetically high-risk patients do not benefit from high dose melphalan and should be offered alternative therapies. Patients and methodsA total of 126 MM patients who received melphalan-based high-dose chemotherapy and ASCT were studied. The major clinical and biological features are summarized in Table 1. After institutional ethics review board approval, bone marrow aspirates were obtained, mononuclear cells enriched for by Ficoll separation and cytospin slides prepared and stored at À701C. To improve FISH scoring specificity, we combined interphase FISH with immunofluorescent detection of the cytoplasmic light chain as previously described. 6 The FISH probes for detection of 13q deletions, t(11;14), t(4;14) and p53 deletions were previously described by us. 6 A total of 100 cells were scored for each abnormality and the percentages of cells with abnormal patterns recorded.Progression-free survival (PFS) and overall survival (OS) were calculated from the transplant date by the KaplanMeier method. Survival curves between risk groups were compared by log-rank tests. Multivariate analysis of PFS and PS was performed using the COX proportional hazards regression model. P-values o0.05 were considered significant. ResultsChromosome 13q deletions were detected by cIg-FISH in 39 of 104...

CD56 is a neural adhesion molecule and expressed in 70-80% cases of multiple myeloma (MM). Lack of CD56 expression has shown to be a poor prognosis in MM patients treated with conventional chemotherapy, but its prognostic relevance in MM treated with high dose chemotherapy and autologous stem cell transplant (ASCT) is not known. CD56 expression was evaluated by immunohistochemistry on bone marrow paraffin embed specimens from 107 MM cases undergoing Melphalan-based high dose therapy and ASCT. CD56 was expressed by the myeloma cells in 71% of the patients. CD56 negative myeloma was associated with bone lesions (p = 0.032), but there was no association with any other biological or genetic risk factors including deletions 13q, p53 and IgH translocations, as evaluated by fluorescence in situ hybridization (FISH). There was no significant difference between CD56 positive and CD56 negative myeloma for progression free or overall survival (p = 0.28 and p = 0.67, respectively). In contrast to reports of CD56 in myeloma treated with conventional chemotherapy, CD56 negativity was not found to confer a poor prognosis in these patients, suggesting Melphalan-based high-dose chemotherapy and ASCT may overcome the adverse influence of CD56 negative myeloma.

On February 19, 2020, the first case of a patient infected with Coronavirus Disease-2019 (COVID-19) was announced in Iran. The number of infected patients increased rapidly, and all health care centers faced an extremely challenging situation in Iran. The centers had to adopt new regulations and approaches to keep their patients and staff safe while providing service to society. Patients diagnosed with a malignancy are at a higher risk for infection with COVID-19 with a poorer prognosis. The Pardis Noor Radiology-Oncology center is a private center in Tehran composed of different departments, including radiation therapy and chemotherapy. Soon after the outbreak, we changed our rules and regulations for patients and staff. This is a report from a private radiology-oncology center in Tehran during the COVID-19 outbreak.

NCT00982059; results.

No abstract

Busulfan and cyclophosphamide (BuCy) are currently the most widely used myeloablative regimen to treat malignancies with allogeneic stem cell transplantation. Fludarabine has considerable efficacy in both immunosuppression and tumor cells killing with a minimal extramedullary toxicity. We evaluated the efficacy of 40 mg/m 2 fludarabine i.v. for 5 days and busulfan 4 mg/ kg/day p.o. for 4 days as myeloablative conditioning regimen in 70 patients (median age 24 years) with acute leukemia or chronic phase of myelogenous leukemia. They all had human leukocyte antigen-matched sibling donors. The patients received 10 lg/kg granulocyte colony stimulating factor (GCSF), 24 h after stem cell infusion until engraftment occurred. Graft-versus-host disease (GVHD) prophylaxis included 3 mg/kg cyclosporine-A i.v. from day À2 to þ 6 followed by 12 mg/kg p.o. until day þ 60. The median time of neutrophil recovery (40.5 Â 109/l) and platelet recovery (420 Â 109/l) were 10 and 12 days, respectively. Mucositis (93%) and hepatic toxicity (16%) resolved with conservative therapy. The incidence of acute GVHD grade I-II and III-IV were 38.6 and 15.7% respectively. Overall survival and disease-free survival were 71 and 64% respectively with 17 months median follow-up for surviving patients. We conclude that FluBu may be used as a substitute for BuCy with almost the same efficacy and with a lower transplant adverse effect but to increase anti-leukemic effects, especially in acute lymphoblastic leukemia patients, it needs some modifications.

No abstract

These results indicate that the analysis of translocations using FISH after in vitro irradiation correlates with clinical response to radiation. This cytogenetic assay should be considered as a potential predictor of radiosensitivity.