Erden Atilla

A review of infectious complications after haploidentical hematopoietic stem cell transplantations

BackgroundAllogeneic hematopoietic stem cell transplantation from haploidentical donor is a feasible option for patients with hematological diseases who lack a suitable HLA-matched donor, but viral and fungal infections are still the most common causes of morbidity and mortality in haploidentical transplantation setting because of delayed immune reconstitution, increased risk of graft vs host disease (GvHD) or systemic steroid use. Therefore, this review will focus on the infectious complications after haploidentical hematopoietic stem cell transplantation (HSCT).Materials and methodsElectronic publications were searched until February 2017 throughout databases, including Pubmed, Cochrane, and Embase. The following keywords were used ‘haploidentical transplantation’, ‘infection’, ‘T cell replete’, and ‘T cell deplete’.ResultsAn increased incidence of bacterial, fungal, or viral infections is detected in haplo-HSCT compared to related, unrelated, or cord blood transplantations. Neutropenia and use of systemic steroid for GvHD and delayed immune reconstitution are important risk factors for infection after haplo-HSCT.ConclusionA shift towards T cell repletes haplo-HSCT with post-transplant cyclophosphamide (CY) for GvHD has been emerged in recent years, in which the incidence of viral and fungal infections is detected to be lower. Prophylaxis and pre-emptive treatment strategies should be applied according to patient status.

Central nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty‐eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow‐up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy‐related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575–580, 2016.

A Review of Myeloablative vs Reduced Intensity/Non-Myeloablative Regimens in Allogeneic Hematopoietic Stem Cell Transplantations

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment option for both malignant and some benign hematological diseases. During the last decade, many of the newer high-dose regimens in different intensity have been developed specifically for patients with hematologic malignancies and solid tumors. Today there are three main approaches used prior to allogeneic transplantation: Myeloablative (MA), Reduced Intensity Conditioning (RIC) and Non-MA (NMA) regimens. MA regimens cause irreversible cytopenia and there is a requirement for stem cell support. Patients who receive NMA regimen have minimal cytopenia and this type of regimen can be given without stem cell support. RIC regimens do not fit the criteria of MA and NMA: the cytopenia is reversible and the stem cell support is necessary. NMA/RIC for Allo-HSCT has opened a new era for treating elderly patients and those with comorbidities. The RIC conditioning was used for 40% of all Allo-HSCT and this trend continue to increase. In this paper, we will review these regimens in the setting of especially allogeneic HSCT and our aim is to describe the history, features and impact of these conditioning regimens on specific diseases.

An overview of hematopoietic stem cell transplantation related thrombotic complications

Thrombotic episodes are far less common than bleeding complications after hematopoietic stem cell transplantation (HSCT). However, they lead to significant morbidity and mortality. These complications are classified into four groups, including venous thromboembolic events (VTE), catheter-induced thrombosis (CIT), transplant-associated thrombotic microangiopathy (TA-TMA) and sinusoidal obstruction syndrome (SOS) or veno-occlusive disease (VOD). The frequency of VTE is increased among patients undergoing HSCT due to some acquired conditions including underlying malignancy, infections, administration of myeloablative conditioning regimens and/or total body irradiation, prolonged hospitalizations leading to immobility and presence of central venous catheters. Central venous catheters provide a convenient long-term venous access during HSCT. But they may lead to VTE and related complications such as pulmonary embolism or post-thrombotic syndrome by inducing endothelial trauma and inflammation. TA-TMA is a heterogeneous, fatal disorder seen within 100days post-transplant and presents with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. SOS or VOD is another life threatening complication occuring within the first 35-40days following a myeloablative regimen and presents with painful hepatomegaly, weight gain and elevated serum bilirubin levels. In this review, we aimed to define the epidemiology, specific risk factors, prevention and management of each group of complications in view of the recent relevant literature.

Successful desensitization of a patient with rituximab hypersensitivity.

Rituximab is a monoclonal antibody which targets CD20 in B cells that is used for the treatment of CD20 positive oncologic and hematologic malignancies. Rituximab causes hypersensitivity reactions during infusions. The delay of treatment or loss of a highly efficient drug can be prevented by rapid drug desensitization method in patients who are allergic to rituximab. We report a low grade B cell non-Hodgkin lymphoma patient with rituximab hypersensitivity successfully treated with rapid drug desensitization. In experienced centers, drug desensitization is a novel modality to break through in case of hypersensitivity that should be considered.

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

Iron overload is an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation (HSCT). In the HSCT setting, pretransplant and early posttransplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload was shown to be related to infections, hepatic sinusoidal obstruction syndrome, mucositis, liver dysfunction, and acute graft-versus-host disease. Hyperferritinemia causes decreased survival rates in both pre- and posttransplant settings. Serum ferritin levels, magnetic resonance imaging, and liver biopsy are diagnostic tools for iron overload. Organ dysfunction due to iron overload may cause high mortality rates and therefore sufficient iron chelation therapy is recommended in this setting. In this review the management of iron overload in adult HSCT is discussed.

Current treatment strategies in relapsed/refractory mantle cell lymphoma: where are we now?

The management of relapsed/refractory mantle cell lymphoma remains challenging. Patients with relapsed mantle cell lymphoma have been treated with multi-agent salvage chemotherapies; however, outcomes are poor. Although there have been studies in the relapse/refractory setting, current data indicate that autologous hematopoietic stem cell transplantation may be an especially useful approach in the front line setting in patients in first complete or partial remission following induction chemotherapy. Allogeneic hematopoietic stem cell transplantation is the only curative option, although reduced intensity conditioning in chemo-sensitive relapse or refractory mantle cell lymphoma provides better survival rates. In addition, bortezomib, lenalidomide, temsirolimus, and ibrutinib have opened a new therapeutic era. More randomized trials should be conducted to evaluate the appropriate use of these new molecules. In this review, I discuss autologous and allo-transplant options as well as the data regarding recently approved novel agents in the relapse/refractory setting in patients with MCL.

A Quasi-Experimental Study Analyzing the Effectiveness of Portable High-Efficiency Particulate Absorption Filters in Preventing Infections in Hematology Patients during Construction.

Objective: The increased risk of infection for patients caused by construction and renovation near hematology inpatient clinics is a major concern. The use of high-efficiency particulate absorption (HEPA) filters can reduce the risk of infection. However, there is no standard protocol indicating the use of HEPA filters for patients with hematological malignancies, except for those who have undergone allogeneic hematopoietic stem cell transplantation. This quasi-experimental study was designed to measure the efficacy of HEPA filters in preventing infections during construction. Materials and Methods: Portable HEPA filters were placed in the rooms of patients undergoing treatment for hematological malignancies because of large-scale construction taking place near the hematology clinic. The rates of infection during the 6 months before and after the installation of the portable HEPA filters were compared. A total of 413 patients were treated during this 1-year period. Results: There were no significant differences in the antifungal prophylaxis and treatment regimens between the groups. The rates of infections, clinically documented infections, and invasive fungal infections decreased in all of the patients following the installation of the HEPA filters. When analyzed separately, the rates of invasive fungal infections were similar before and after the installation of HEPA filters in patients who had no neutropenia or long neutropenia duration. HEPA filters were significantly protective against infection when installed in the rooms of patients with acute lymphocytic leukemia, patients who were undergoing consolidation treatment, and patients who were neutropenic for 1-14 days. Conclusion: Despite the advent of construction and the summer season, during which environmental Aspergillus contamination is more prevalent, no patient or patient subgroup experienced an increase in fungal infections following the installation of HEPA filters. The protective effect of HEPA filters against infection was more pronounced in patients with acute lymphocytic leukemia, patients undergoing consolidation therapy, and patients with moderate neutropenia.

Allogeneic Transplantation In Chronic Myeloid Leukemia And The Effect Of Tyrosine Kinase Inhibitors On Survival, A Quasi-Experimental Study.

Objective: Tyrosine kinase inhibitors (TKIs) have changed the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia (CML). Therefore, we aimed to evaluate the effect of TKIs on allo-HSCT in CML. Materials and Methods: In this quasi-experimental study, we compared patient, disease, and transplantation characteristics as well as allo-HSCT outcomes between the pre-TKI era (before 2002) and the post-TKI era (2002 and later) in patients with CML. A total of 193 allo-HSCTs were performed between 1989 and 2012. Results: Patients in the post-TKI era had more advanced disease (>chronic phase 1) at the time of transplant and more frequently received reduced-intensity conditioning compared to patients in the pre-TKI era. Relapse/progression occurred more frequently in the year ≥2002 group than in the year <2002 group (48% vs. 32% at 5 years, p=0.01); however, overall survival (OS) was similar in these two groups (5-year survival was 50.8% vs. 59.5%, respectively; p=0.3). TKIs (with donor lymphocyte infusions or alone) for treatment of relapse after allo-HSCT were available in the post-TKI era and were associated with improved OS. While the rates of hematologic remission at 3 months after allo-HSCT were similar between TKI eras, patients having remission had better disease-free survival (DFS) [relative risk (RR): 0.15, confidence interval (CI) 95%: 0.09-0.24, p<0.001] and OS (RR: 0.14, CI 95%: 0.09-0.23, p<0.001). Male allo-HSCT recipients had worse DFS (RR: 1.7, CI 95%: 1.2-2.5, p=0.007) and OS (RR: 1.7, CI 95%: 1.1-2.6, p=0.02) than females. Conclusion: TKIs are an effective option for the treatment of relapse after allo-HSCT in CML. Hematologic remission after allo-HSCT is also an important factor for survival in CML patients.

A review of late complications of allogeneic hematopoietic stem cell transplantations

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is an effective and curative treatment of different malignant and non‐malignant diseases. Early transplant‐related mortality after allo‐HSCT has decreased with reduced‐intensity conditioning regimens and effective anti‐infectious treatments, but late transplant‐related mortality is still a problem. Physicians are now paying more attention to late complications that may worsen the quality of life of many transplant recipients. Chronic graft versus host disease (cGVHD) is one of the major causes of late transplant‐related mortality after allo‐HSCT. This review discusses recent advances that have been made in clinical evaluation and treatment of late transplant‐related complications including cGVHD. The different sites of involvement are organs, especially the skin and eye, and the gastrointestinal, endocrinologic, metabolic, renal, cardiologic, pulmonary, connective tissue, and neurological systems. In addition, this review includes infections and secondary malignancies in post‐transplant settings that worsen quality of life in long‐term follow‐ups.