Tigran Torosian

Disseminated adenovirus disease in immunocompromised patient successfully treated with oral ribavirin: a case report

In patients with immunological disorders, adenovirus infections are associated with significant rates of morbidity and mortality. Only few hematological units use molecular virological methods, such as polymerase chain reaction, for surveillance of adenovirus infection, and treatment strategies have never been evaluated in multicenter clinical trials. This report describes the detection and treatment of human adenovirus (HAdVs) disseminated disease in the case of a 46-year-old immunocompromised female having myelodysplastic syndrome with refractory cytopenia with multilineage dysplasia: International Prognostic Scoring System 1. Serum and urine samples were tested for the presence of adenoviral DNA using the quantitative real-time polymerase chain reaction (PCR) assay. For additional confirmation, sequencing of PCR products was also performed. With real-time PCR, we detected HAdV DNA in both serum and urine samples. The viral level constantly decreased with applied oral ribavirin therapy. As the result of sequencing, HAdVs type 11 was determined. Surveillance of adenovirus by real-time PCR is useful in detecting and monitoring disseminated HAdV infection; it is a potential standard diagnostic approach that could assist clinicians to decide whether antiviral therapy ought to be administered.

Prevalence of human herpesvirus 6 antibodies and DNA in allogeneic stem cell transplant patients: two-year single centre experience

Introduction:Human herpesvirus 6 (HHV-6) has been recognized as a potentially significant pathogen in hemopoietic stem cell transplant (HSCT) recipients. Different clinical manifestations have been described, including fever, skin rash, bone marrow suppression, and encephalitis.Materials and Methods:A retrospective review of a group of 26 adult recipients of allogeneic HSCTs was conducted. Serum samples taken before transplant were examined for the presence of specific anti-HHV-6 IgM and IgG antibodies. After transplantation, quantitative real-time PCR was used to determine viral load in plasma samples from days 0–80 post-transplant.Results:HHV-6 DNA was detected in plasma samples in 8 (30%) of the 26 recipients between days 18 and 40 after transplantation. All of them developed fever of unknown origin and over 50% had graft-versus-host disease features. Three individuals from this group died during detectable HHV-6 viremia. Another two recipients showed a single positive PCR result at a later time. Infection with HHV-6 was thus confirmed in 10 (38.5%) of the 26 graft recipients.Conclusions:There is a high frequency of detectable HHV-6 viral load in stem cell transplant recipients in Poland. Further investigation to monitor HHV-6 reactivation in graft recipients will be important to improve outcome for these patients.

A multidisciplinary team approach to the management of patients with suspected or diagnosed invasive fungal disease

Implementation of evidence-based guidelines for the treatment of invasive fungal disease (IFD) requires collaboration among numerous clinical and laboratory services, as partners in patient care. The multidisciplinary team (MDT) approach has emerged as a way of providing comprehensive medical care by bringing together professionals from a wide range of disciplines in a coordinated and effective manner. Here, we propose an MDT model for IFD management aimed at facilitating communication among consultants, adherence to clinical pathways and optimized use of resources available at each centre.

Case-adjusted bortezomib-based strategy in routine therapy of relapsed/refractory multiple myeloma shown to be highly effective—A report by Polish Myeloma Study Group

The observational study was aimed at evaluating response, survival and toxicity of bortezomib-based, case-adjusted regimens in real-life therapy of 708 relapsed/refractory MM patients. Bortezomib was combined with anthracyclines, steroids, thalidomide, alkylators or given in monotherapy. The ORR was 67.9% for refractory and 69.9% for relapsed MM. The median PFS was 14 months and OS 57 months. Patients responding to the therapy had the probability of a 4-year OS at 67.0%. No toxicity was noted in 33.1% of patients. Severe events (grade 3/4) were reported in 35.9% of patients: neurotoxicity (16.7%), neutropenia (9.2%), thrombocytopenia (8.5%), and infections (6.5%). Bortezomib-based, case-adjusted regimens are in real-life practice effective in salvage therapy offering reliable survival with acceptable toxicity for relapsed/refractory MM patients.

Human Herpesvirus 7 in Allogeneic Hemopoietic Stem Cell Transplant Recipients in the Central Clinical Hospital in Warsaw: A Three-Year Survey

Objectives: Human herpesvirus 7 (HHV-7) is spread worldwide and has been described as a potential pathogen in immunosuppressed patients. Different clinical manifestations have been described including fever and skin rash; HHV-7 may also be a possible cofactor for cytomegalovirus disease in transplant recipients. Materials and Methods: A retrospective review of a group of 58 adult recipients of allogeneic hemopoietic stem cell transplantation was made. Serum samples taken in the range of 0–180 days after transplant were examined for presence of specific HHV-7 sequences using the quantitative real-time PCR method. Results: HHV-7 DNA was detected in plasma samples in 26 (45%) of the 58 recipients between day 20 and day 65 of transplantation. All of them developed fever of unknown origin; also HHV-5 DNA was detected in plasma samples collected from 11 HHV-7-positive patients. None of the described individuals died during detectable HHV-7 or HHV-5 viremia periods. Conclusions: There is a high frequency of detectable HHV-7 viral load in allogeneic stem cell transplant recipients in Poland. Limited availability and sensitivity of serological methods along with the necessity of rapid introduction of antiviral treatment has forced the development of molecular diagnostics. Furthermore, establishment of appropriate procedures for monitoring active HHV-7 infection is important to clarify the virus infection in transplant recipients.

Triple transplantation of autologous peripheral blood stem cells each time following conditioning with 100 mg/m2 of melphalan for multiple myeloma patients in poor performance status ☆

Approximately one third of multiple myeloma patients (below 60 years) are diagnosed either in advanced disease or with significant comorbidities. Many other patients referred to transplant centers have already been heavily pretreated with multiple courses of various conventional chemotherapies. These patients are frequently in bad or even grave clinical condition; they are unlikely to survive standard high-dose melphalan (200 mg/m(3)) chemotherapy and autologous hematopoietic stem cell transplantation. Palumbo et al reported a protocol for elderly patients that utilized reduced conditioning (melphalan 100 mg/m(2) three times at 2-month intervals, each time supported by autologous hematopoietic rescue). We have used this protocol as a start to develop a method to induce a remission in the aforementioned subgroup of myeloma patients. Patients with stage III disease and WHO performance status 2 or higher are treated with one or two cycles of cyclophosphamide (2 to 4 g/m(2)) and undergo peripheral blood stem cells collection. Subsequently, they are treated with three to four doses of melphalan (100 mg/m(2)) at 8- to 12-weeks intervals each time supported by infusion of peripheral blood stem cells. To date 13 patients have been entered into the protocol. With one exception of transiently stable disease, the remaining patients obtained at least partial remission and three, complete remission. The compliance was good and better with each subsequent course. For half of the patients the problem was a short duration of response. This method when developed may offer a new treatment alternative for a subgroup of high-risk multiple myeloma patients.

Bone marrow harvest from unrelated donors – up to date methodology

Bone marrow harvesting is one of the essential sources of stem cells for hematopoietic stem cell transplantation. We describe here the current “up‐to‐date” standard of the bone marrow harvest in unrelated stem cell donors.

High-Dose Melphalan and Autologous Hematopoietic Stem Cell Transplantation in Primary Amyloidosis: Single-Center Results

BACKGROUND Systemic immunoglobulin light-chain amyloidosis (AL) is a plasma cell dyscrasia resulting in multisystem organ failure and death. Autologous hematopoietic stem-cell transplantation (ASCT) has been widely used to treat patients with AL. However, treatment-related mortality remains high and reported series are subject to selection bias. METHODS To define the role of patient selection in stem cell transplantation, we evaluated 24 consecutive AL patients transplanted at our center. RESULTS Complete hematologic response was achieved in all 20 patients surviving >100 days posttransplantation. The 1-year overall survival (OS) rate after ASCT was 78.5%. The 5- and 10-year progression-free and OS rates were 57% and 47%, respectively. Treatment-related deaths owing to cardiovascular problems occurred in 16% of cases. CONCLUSION ASCT for AL amyloidosis can be safely performed in experienced transplantation centers, and increased risk is associated mainly with cardiovascular system involvement.

Lack of persistent remission following initial recovery in patients with type 1 diabetes treated with autologous peripheral blood stem cell transplantation

AIMS To assess metabolic control in patients with newly diagnosed type 1 diabetes mellitus who underwent immunoablation followed by autologous peripheral blood stem cell transplantation (APBSCT) as a treatment of diabetes. METHODS APBSCT was performed in 23 patients. Control group comprised 8 non-APBSCT patients in whom after diagnosis insulin therapy was initiated. Fasting plasma glucose, glycated hemoglobin, fasting and postprandial C-peptide were assessed in all subjects and continuous glucose monitoring was performed at 6th, 12th, 24th, 36th, 48th month after transplantation. The APBSCT group was observed for 72 months. RESULTS Six months after the procedure, 22 of 23 transplant patients remained insulin-free, but after 6 years, there was only one APBSCT insulin-free patient. Good glycemic control was observed in all patients throughout the observation period, although fasting plasma glucose in control group was significantly higher in comparison with the both transplanted groups up to the 36th month. HbA1c values were significantly lower in the insulin-free group only at the 24th and 36th month. Fasting and postprandial C-peptide concentrations were higher in APBSCT group as compared with control group. The most serious adverse event was a fatal case of Pseudomonas aeruginosa sepsis. CONCLUSIONS The effectiveness of APBSCT as a treatment for newly diagnosed DM1 seems to be limited in time. The metabolic control of APBSCT patients is similar to conventionally treated patients. The lower fasting plasma glucose and higher C-peptide achieved with APBSCT seem to not exceed the risks associated with the procedure.

Evaluation of relative anti-myeloma activity of high-dose melphalan followed by the first peripheral blood stem cell transplantation, as compared with the second transplantation, and to VAD chemotherapy.

Current treatment in multiple myeloma consists of three courses of chemotherapy in low doses with subsequent hematopoietic stem cell mobilization to the peripheral blood using high-dose cyclophosphamide, collection and conditioning with high-dose chemotherapy (melphalan) followed by retransplantation of autologous peripheral blood stem cells (PBSCT). Only a few studies compare the effects of different phases of therapy on parameters, such as monoclonal immunoglobulin level and the presence of malignant CD38(+) and CD56(+) cells in blood and marrow. The aim of this study was to compare the effects of these two major phases of treatment (conventional and high dose) in the same patients, and furthermore, to compare the effects of the second course of high-dose therapy followed by PBSCT with the effects of the first one. Fifteen patients were included in the study. On average, conventional chemotherapy only slightly reduced the values of all disease markers. In contrast, high-dose therapy resulted in a dramatic effect, rapidly normalizing the values of all parameters. The effects of second PBSCT were only modest compared to the first. These data suggest that high-dose therapy is an efficient method to reduce tumor load in multiple myeloma. Conventional-dose chemotherapy may be simply a waste of time for some patients and may be either omitted or administered after high-dose therapy to consolidate remission.