Lower Body Mass Index and Prognostic Nutritional Index Are Associated with Poor Posttransplant Outcomes in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.

INTRODUCTION: Pretransplant inflammatory and nutritional status has not been widely explored in terms of its impact on autologous hematopoietic stem cell transplantation (auto-HSCT) outcomes in lymphoma patients. We aimed to evaluate the impact of body mass index (BMI), prognostic nutritional index (PNI), and C-reactive protein to albumin ratio (CAR) on auto-HSCT outcomes. METHODS: We retrospectively analyzed 87 consecutive lymphoma patients who underwent their first auto-HSCT at the Adult Hematopoietic Stem Cell Transplantation Unit at Akdeniz University Hospital. RESULTS: The CAR had no impact on posttransplant outcomes. PNI ≤50 was an independent prognostic factor for both shorter progression-free survival (PFS) (hazard ratio [HR] = 2.43, p = 0.025) and worse overall survival (OS) (HR = 2.93, p = 0.021), respectively. The 5-year PFS rate was significantly lower in patients with PNI ≤50 than in patients with PNI >50 (37.3% vs. 59.9%, p = 0.003). The 5-year OS rate in patients with PNI ≤50 was significantly low when compared with patients who had PNI >50 as well (45.5% vs. 67.2%, p = 0.011). Patients with BMI <25 had higher 100-day transplant-related mortality compared with patients with BMI ≥25 (14.7% vs. 1.9%, p = 0.020). BMI <25 was an independent prognostic factor associated with shorter PFS and OS (HR = 2.98 [p = 0.003], HR = 5.06 [p < 0.001], respectively). The 5-year PFS rate was significantly lower in patients with BMI <25 than patients with BMI ≥25 (40.2% vs. 53.7%, p = 0.037). Similarly, the 5-year OS rate in patients with BMI <25 was significantly inferior compared to patients with BMI ≥25 (42.7% vs. 64.7%, p = 0.002). CONCLUSION: Our study confirms that lower BMI and CAR have negative impacts on auto-HSCT outcomes in lymphoma patients. Furthermore, higher BMI should not be considered an obstacle for lymphoma patients who need auto-HSCT; conversely, it could be an advantage for posttransplant outcomes.

The Prognostic Impact of Pretreatment Geriatric Nutritional Risk Index in Patients with Diffuse Large B-Cell Lymphoma.

The prognostic value of the geriatric nutritional risk index (GNRI) is not clear in patients with diffuse large B-cell lymphoma (DLBCL). This study was designed to analyze the GNRI in DLBCL patients and to investigate its prognostic value in DLBCL. The archive records of DLBCL patients between 2008 and 2020 at the Akdeniz University Hospital were retrospectively analyzed. A total of 206 patients with DLBCL were recruited and classified into two GNRI-based groups based on nutrition status. The GNRI cut off value was determined by ROC analysis. In the univariate Cox regression analysis for overall survival (OS), age, lactate dehydrogenase, B symptoms, infiltration of bone marrow, and the GNRI were determined as prognostic factors for mortality. The OS of patients with a GNRI ≤104.238 was significantly lower than that of patients with a GNRI >104.238 (p = 0.001). The progression-free survival (PFS) of patients with GNRI ≤104.238 was significantly lower compared to the patients with GNRI >104.238 (p = 0.010). Based on the results of the present study with a relatively large hospital-based cohort, the GNRI can be recommended for use as an independent prognostic marker for OS and PFS in patients with DLBCL.

Long-Term Complete Clinical and Hematological Response With Bortezomib: The Report of a Case With TEM(P)I Syndrome and a Review of the Literature.

TEMPI syndrome was first defined in 2011 and classified as a plasma cell neoplasm with associated paraneoplastic syndrome in 2016. The pathogenesis of the syndrome is not well understood. Recognition of a combination of telangiectasia, erythrocytosis with a high erythropoietin level, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunt is the first step in managing the disease. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other dermatological, renal, and pulmonary disorders. Without early diagnosis significant disability results from the pulmonary damage. The article we present here describes a clinical case of TEMPI-syndrome in a 58-year-old woman, which illustrates the difficulties associated with the timely recognition of this unusual disease. Here, we also review the clinical features of TEMPI syndrome, differential diagnosis and available treatment options, based on current literature. Although limited in number, with the addition of new patients to the literature, TEMPI syndrome is evolving into a well characterized multisystem syndrome. This rare disorder should not be missed, especially if the patient has a putative diagnosis of essential telangiectasia with a monoclonal gammopathy and polistemia. Increasing the awareness of clinicians about the disease and adding new patient data to the literature may contribute to a better understanding of the pathophysiology of the disease and standardization of treatment.

Outcomes of stem cell mobilization and engraftment in patients with multiple myeloma according to CD56 expression status.

BACKGROUND: The molecular mechanism underlying the mobilization and engraftment of CD34+ cells is poorly understood. The most relevant factors in the regulation of stem cell release and engraftment include chemokines, adhesion molecules, and chemokine receptors. Previously, it was suggested that the absence of CD56 expression could be used as a predictive factor for mobilization failure at the time of diagnosis. Here, we investigated the effect of CD56 expression status on both mobilization and engraftment processes. Additionally, other factors affecting mobilization and engraftment efficacy were investigated. METHODS: Data from 79 multiple myeloma patients undergoing autologous stem cell transplantation between 2015 and 2020 were analyzed for peripheral stem cell mobilization and posttransplant neutrophil and platelet engraftment according to CD56 expression on myeloma cells. RESULTS: No difference in either the median number of CD34+ cells collected or time to engraftment was found between the CD56+ and CD56- groups. The age of the patients (p = 0.025) and peak number of circulating CD34+ cells in peripheral blood (p = 0.005) were important predictors for a higher number of collected CD34+ cells. The average time to recovery of leukocytes and platelets after transplantation was markedly correlated with the number of transplanted stem cells and peak number of circulating CD34+ cells in peripheral blood, respectively (p = 0.049 and p = 0.003). CONCLUSIONS: Our results indicated no effect of CD56 expression status on the mobilization and engraftment of PBSCs. Our results also support the notion that the peak number of circulating CD34+ cells in peripheral blood is clinically important for rapid platelet engraftment following HPC transplantation.

Recurrent arthritis as an unexpected side effect associated with azacitidine in a patient with myelodysplastic syndrome.

INTRODUCTION: Hypomethylating agents have confirmed efficacy for myelodysplastic syndrome and acute myeloid leukemia and are widely used. Although arthralgia is common side effect associated with hypomethylating agents, arthritis has not been reported previously. CASE REPORT: We present the first recorded patient with arthritis after azacitidine treatment. The patient we presented here had severe cytopenias requiring transfusion with erythrocyte and platelet suspensions, and a complete hematological response was obtained for myelodysplastic syndrome after three cycles of azacitidine (AZA) treatment. However, interestingly, after each AZA treatment cycle, the patient had recurrent attacks of arthritis. MANAGEMENT AND OUTCOMES: The episodes of arthritis were possibly acute flares of pre-existing crystal-induced arthritis, as exhibited with azacitidine treatments and were managed effectively with nonsteroidal anti-inflammatory drugs. DISCUSSION: Because it is a rare condition, clinicians should not overlook AZA as a possible cause of arthritis exacerbations when arthritis of unknown etiology develops in patients treated with AZA.

Evaluation of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in Turkey: a multicenter retrospective analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings.

Prognostic impact of the psoas muscle index, a parameter of sarcopenia, in patients with diffuse large B-cell lymphoma treated with rituximab-based chemoimmunotherapy.

Muscle mass, defined as the psoas muscle index (PMI), is an important parameter of sarcopenia and it has been shown to be a prognostic factor of non-hematological cancers. This study aimed to investigate the prognostic impact of sarcopenia defined using PMI measurement in patients with diffuse large B-cell lymphoma treated with R-CHOP. We retrospectively investigated the impact of pretreatment PMI on survival and response to treatment. One hundred and twenty patients with DLBCL were included in the study, of whom 65 had baseline sarcopenia according to the defined PMI cutoffs. Sarcopenic patients displayed a worse response to treatment compared with non-sarcopenic patients. In a multivariate analysis, sarcopenia remained predictive of outcomes for overall survival (p = .009), progression free survival (p = .028), and response to treatment (p = .006). Sarcopenia defined by evaluating PMI is a simple and routinely applicable method that can predict poor outcomes in patients with DLBCL.

Minimal Residual Disease Eradication by Azacitidine Maintenance in a Patient with Core-Binding Factor Acute Myeloid Leukemia.

Although core-binding factor AML (CBF-AML) has a favorable outcome, disease relapses occur in up to 35% of patients. Minimal residual disease (MRD) monitoring is one of the important tools to enable us to identify patients at high risk of relapse. Real-time quantitative PCR allows MRD to be measured with high sensitivity in CBF-AML. If the patient with CBF-AML is in complete morphologic remission but MRD positive at the end of treatment, what to do for those is still uncertain. Preemptive intervention approaches such as allogeneic hematopoietic stem cell transplantation or intensive chemotherapy could be an option or another strategy might be just follow-up until overt relapse developed. Although using hypomethylating agents as a maintenance therapy has not been widely explored, here, we report a case with CBF-AML who was still positive for MRD after induction/consolidation therapies and whose MRD was eradicated by azacitidine maintenance.

Comparison of Various Hematopoietic Stem Cell Mobilization Regimens in Patients with Lymphoma and Myeloma.

BACKGROUND: The aim of this study was to evaluate the efficacy of cyclophosphamide-based (CB) and platinum-based (PB) chemotherapy regimens for hematopoietic stem cell mobilization in patients with Multiple Myeloma (MM), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL) and the less well-known IEV (iphosphamide, epirubicin, etoposide) regimen in terms of stem cell harvesting competence, factors affecting stem cell com-petence, and toxicity. METHODS: A retrospective evaluation was made of 203 patients (94 MM, 37 HL, and 72 NHL) with peripheral blood stem cell mobilization in different chemotherapy regimens between 2000 and 2010 at the Department of He-matology, Faculty of Medicine, Akdeniz University. RESULTS: There were no differences between CB or PB mobilization regimens and IEV chemotherapy schema in terms of sufficiency of peripheral stem cell harvest, which was predefined as the collected number of peripheral stem cells ≥ 3 x 106/kg for single hematopoietic stem cell transplantation (HSCT) and ≥ 5 x 106/kg for tandem HSCT. There were also no significant differences between low dose cyclophosphamide, high dose cyclophosphami-de, and HCVAD (cyclophosphamide, vincristine, dexamethasone, methotrexate, cytosine arabinoside [ARA-C]) among the subgroups of cyclophosphamide-based regimens. The number of peripheral blood stem cells collected using ESHAP (ethoposide, methylprednisolone, ARA-C, cisplatin), a platin-based regimen, was significantly higher than the other platin-based regimens including DHAP (dexamethasone, ARA-C, cisplatin), ICE (iphosphamide, carboplatin, ethopocide), and EDAP (etoposide, dexamethasone, ARA-C, cisplatin). The toxicity profiles of CB, PB, and IEV chemotherapies were similar. To determine the independent predictors of the efficacy of the stem cell harvest procedure and collected stem cell count, age, diagnosis, duration of disease, number of treatment sequences before mobilization, and number of rescue regimens were included into multiple logistic regression analysis. However, no correlations were determined. CONCLUSIONS: The results of this study provide information on the effectiveness of different stem cell mobilization regimens. Although no significant difference was determined between the three major chemotherapy regimens, the ESHAP regimen appears to be the preferred treatment regimen for stem cell mobilization in selected lymphomas.

Investigation of seasonal frequency and pathogens in febrile neutropenia.

BACKGROUND: In patients with hematological malignancies, febrile neutropenia (FEN) is the most frequent complication and the most important cause of mortality. Various risk factors have been identified for severe infection in neutropenic patients. However, to the best of our knowledge, it is not defined whether there is a change in the risk of febrile neutropenia according to seasons. The first aim of study was to determine the difference in frequency of febrile neutropenic episodes (FNEs) according to months and seasons. The second aim was to document isolated pathogens, as well as demographical and clinical characteristics of patients. METHODS: In the study, 194 FNEs of 105 patients who have been followed with hematological malignancies between June 2013 and May 2014 were evaluated retrospectively. RESULTS: Although the number of FNEs increased in autumn, there was no significant difference in frequency of FNEs between months (p = 0.564) and seasons (p = 0.345). There was no isolated pathogen in 54.6% of FNEs. In 45.4% of 194 FNEs, pathogens were isolated. Of all pathogens, 50.4% were gram negative bacteria, 29.2% were gram positive bacteria, 13.3% were viruses, 5.3% were fungi, and 1.8% were parasites. CONCLUSIONS: The frequency of FEN does not change according to months or seasons. Also, the relative proportions of different pathogens in the cause of FEN do not vary according to seasons.

Efficacy of 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography/Computerized Tomography for Bone Marrow Infiltration Assessment in the Initial Staging of Lymphoma.

OBJECTIVE: Currently 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computerized tomography (PET/CT) is being successfully used for staging and follow-up of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). Various studies have demonstrated that PET/CT effectively detects bone marrow involvement (BMI) and is concordant with bone marrow biopsy (BMB) findings, thus it is deemed as a complementary method. This study was aimed to evaluate18F-FDG-PET/CT efficiency for detection of BMI in HL and NHL. METHODS: The study included 172 lymphoma cases who were admitted to Akdeniz University Medical School Department of Nuclear Medicine for initial staging with PET/CT. Visual and semiquantitative assessments were performed for PET/CT scan findings of the cases. The maximum standard uptake (SUVmax) value was the quantitative parameter used for 18F-FDG-PET scan. In visual assessment, bone marrow metabolic activity that is greater than the liver was considered as pathologic. For semiquantitative assessment, regions of interest were drawn for SUVmax estimation, which included iliac crest in cases with diffusely increased metabolic activity and the highest activity area in cases with focal involvement. BMB was considered as the reference test. RESULTS: On visual assessment of all the cases, PET/CT was found to yield 31% sensitivity and 85% specificity rate for detection of BMI. On visual assessment of HL cases, sensitivity rate was determined as 80%, and specificity as 78%, while in NHL cases the corresponding values were 24% and 90%, respectively. On semiquantitative assessment of HL cases, considering SUVmax≥4, sensitivity was found as 80% and specificity as 68%. In NHL patients, considering SUVmax≥3.2, sensitivity rate was detected as 65% and specificity as 58%. CONCLUSION: In this study, a moderately high concordance was observed between PET/CT and BMB findings. PET/CT appears to be a significant method for detecting BMI. Although PET/CT is not a substitute for BMB, we suggest it can be used as a guide to biopsy site and a complementary imaging technique for BMB.

Consideration of difficulties and exit strategies in a case of face allotransplantation resulting in failure.

We describe the first rescue procedure in a case of total face allotransplantation. The recipient was a 54-year-old man with severe disfigurement of the entire face following an accidental gunshot injury 5 years previously. The large defect included the maxilla, mandible, and mid-face. Full face procurement was performed from a multiorgan cadaveric donor and was allotransplanted to the recipient. The post-transplant induction immunosuppressive regimen included ATG combined with tacrolimus, mycophenolate mofetil, and prednisone, while maintenance was provided by the last three of these. Although the early postoperative period was uneventful, squamous cell carcinoma developed in the upper and lower extremities in the fifth postoperative month, and post-transplant lymphoproliferative disorder (PTLD) occurred in the sixth month postoperatively. Malignancies were treated, involving both surgical and medical approaches. The patient developed opportunistic pulmonary and cerebellar aspergillosis. In order to reduce the adverse affects and metabolic and immunological load, the transplanted face was removed and replaced with a free flap. Although the early postoperative period was promising, with the transferred flap surviving totally and all vital signs and general status appearing to be improving, the patient was eventually lost due to complicated infectious and metabolic events. Although this case was unsuccessful, we suggest that the immunological and metabolic load should be reduced as soon as stable medical conditions are established in case of diagnosis of a situation involving a high rate of mortality, such as PTLD and untreatable opportunistic infections. This should include withdrawal of all immunosuppressive drugs and removal of all allotransplanted tissues.

Azacitidine versus decitabine in patients with refractory anemia with excess blast-Results of multicenter study.

The present study aimed to compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndrome (MDS). A total of 88 patients diagnosed with refractory anemia with excess blast (RAEB) treated with azacitidine (n=57) or decitabine (n=31) were evaluated. Comparisons between azacitidine and decitabine groups were performed in the whole cohort, and in a 1:1 propensity score-matched cohort in order to reduce the simple selection bias. Patients who received azacitidine or decitabine had comparable overall response rates in both the unmatched (49.1% vs. 64.5%, p=0.166) and the propensity-matched cohorts (52% vs. 68%, p=0.248). The cumulative incidence of AML transformation at one year was comparable between azacitidine and decitabine in the unmatched (24.0% vs. 31.3%, p=0.26) and in the propensity-matched cohorts (18.7% vs. 31.5%, p=0.11). There was no difference in terms of transfusion requirement, febrile neutropenia episodes or the need for antifungal use during the treatment cycles in the propensity-matched cohort. The median overall survival was 20.4 months for azacitidine and 16.8 months for decitabine (p=0.59). Finally, we found that at least a four-cycle treatment with any HMA was a favorable factor. In conclusion, both azacitidine and decitabine have similar efficacy and toxicity profiles in the treatment of MDS-RAEB.

C-MYC and BCL2 translocation frequency in diffuse large B-cell lymphomas: A study of 97 patients.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. MYC and BCL2 rearrangements have been reported in a proportion of DLBCLs, where they may be associated with an adverse clinical outcome. The aim of this study was to determine the frequency of MYC and BCL2 translocations in DLBCL and assess the prognostic impact in DLBCL patients. MATERIALS AND METHODS: In the present study, we evaluated the expression patterns of CD 10, BCL6, and MUM 1 by immunohistochemistry in 121 cases with DLBCL in tissue microarray (TMA): 62 cases in germinal center B-cells (GCBs); and 59 cases in activated B-cells (ABCs) of which 60 were females and 61 were males. MYC and BCL2 rearrangements were investigated by interphase fluorescence in situ hybridization on TMAs in 97 DLBCLs. RESULT: MYC rearrangements were observed in 11 of 97 cases. There was no association with other clinical features, including age, sex, and nodal/extranodal disease. MYC rearrangement was associated with significantly worse overall survival (P < 0.01). BCL2 rearrangements were observed in 14 of 97 cases. There was no association with other clinical features including age and sex. BCL2 rearrangement had a worse outcome (P < 0.01). MYC and BCL2 rearrangements were observed in 3 of 97 cases with the age of  53 (female), 53, 63 years old, respectively, died in 24, 18, and 35 months after the diagnosis. Two cases had primary nodal and one case primary extranodal presentations. All these patients had stage IV disease. CONCLUSION: We concluded that C-MYC and BCL2 may contribute to aggressive transformation, and more mechanism-based therapy should be explored. Targeted therapies involving these rearrangements and its associated pathways may change the fate of DLBCLs. Analysis of MYC gene rearrangement along with BCL2 is critical in the identification of high-risk patients with poor prognosis.

inv (4)(p13q13) in patient with essential thrombocythemia: A case report.

The inv (4)(p13q13) cytogenetic abnormality is uncommon in hematologic malignancies. So far, it has not been previously reported in patients with essential thrombocythemia (ET). We report a first case of ET with inv (4)(p13q13) karyotype in a 69-year-old female patient who developed myelofibrosis at follow up. Conventional cytogenetic analysis from a bone marrow sample showed 46, XX, inv (4)(p13q13) [3]/46, XX [4] at diagnosis and subsequent analysis revealed the same abnormal karyotype during the myelofibrosis phase (46, XX, inv (4)(p13q13) [13]/46, XX [26]). The prognostic significance of this chromosomal abnormality is unknown.

T-cell prolymphocytic leukemia presenting with leukemic serous effusion in a prostate cancer patient.

T-cell prolymphocytic leukemia (T-PLL) is highly aggressive mature postthymic lymphoproliferative disorder, which is characterized by several clinical features. Leukemic prolymphocytes are found in the peripheral blood, bone marrow, lymph nodes, spleen, liver, and sometimes skin. T-PLL and solid tumor coincidence was reported by only four previous cases. Solid tumor components included breast cancer, classic Kaposi sarcoma, gastric cancer, and lung cancer in those cases. We report the first case of T-PLL, an extremely rare disease, presented with serous effusion in an elderly prostate cancer patient in literature.

Previously Unreported Chromosomal Aberrations of t(3;3)(q29;q23), t(4;11)(q21;q23), and t(11;18)(q10;q10) in a Patient with Accelerated Phase Ph+ CML.

Chronic myelogenous leukemia (CML) is a clonal hematological disorder, which is characterized by the presence of the classical or variant Philadelphia translocations. During the progression to blastic phase of the disease secondary chromosomal abnormalities may emerge. Such secondary chromosomal abnormalities are nonrandom, the more frequent ones being trisomy 8 and 19, supernumerary i(17q), and extra Philadelphia chromosomes. Furthermore, a minor percentage of the patients may acquire different secondary chromosomal abnormalities including translocations between other chromosomes. We report here a patient with Ph+ CML presenting secondary chromosomal abnormalities including t(4;11)(q21;q23), t(3;3)(q29;q23) and t(11;18)(q10;q10) during the course of CML progression.