Peripheral blood stem cells mobilization in patients with relapsed or refractory lymphomas: A single-center experience.

CONTEXT: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is an established treatment for chemosensitive patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). AIMS: We present the results of using different salvage chemotherapy plus granulocyte colony stimulating factor (G-CSF) for mobilization of peripheral blood stem cells in R/R lymphoma patients. SUBJECTS AND METHODS: For salvage chemotherapy, 93 patients received platinum-containing regimens, 4 patients received cytarabine-containing regimens, and 5 patients received other regimens. Patient distributions were HL (n = 35) and NHL (n = 67). RESULTS: In 87.2% of patients, first mobilization trial was successful (>2 × 106 CD34+ cells/kg). In 58.8% of patients, first apheresis season >5 × 106 CD34+ cells/kg collections was achieved. All 12.7% of patients were poorly mobilized at the first mobilization. There was no statistical difference between the previous chemotherapy numbers and failed mobilization (P > 0.05). Five patients who were poorly mobilized and 4 patients who were successfully mobilized underwent a previous radiotherapy (P < 0.05). Thirteen patients who were poorly mobilized in the first mobilization underwent a platinum-containing salvage regimen. At the time of the first mobilization, the average peripheral CD 34 counts in the successfully mobilized group were statistically higher than that in the poorly mobilized group (P < 0.01). CONCLUSIONS: We demonstrated that peripheral CD 34 cell count in the peripheral blood on the first apheresis day was a significant factor for more stem cell mobilization, fewer apheresis sessions, less volume, and earlier neutrophil engraftment for patients with R/R lymphoma and eligible for AHSCT. The history of the previous radiotherapy was a significant factor for poor mobilization.

International Forum: The Turkish perspective on apheresis activity: The Turkish apheresis registry report.

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications.

A Retrospective Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens Before Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Lymphoma Patients.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is considered the standard therapy for patients with relapsed lymphoma. The aim of our study is the comparison of mitoxantrone-melphalan and BEAM (carmustine, etoposide, cytarabin and melphalan) conditioning regimens before autologous hematopoietic stem cell transplant in patients with lymphoma. This study has been performed in a retrospective manner. Hundred and two patients with relapsed/refractory Hodgkin lymphoma (n = 35) and non-Hodgkin lymphoma (n = 67) who underwent high-dose treatment followed by AHSCT at Memorial Sisli Hospital between 2013 and 2018 were evaluated. We retrieved data on patient demographics, disease status and post AHSCT outcomes. For conditioning regimen 52 patients received mitoxantrone (60 mg/m2 × 1 day) and melphalan (180 mg/m2 × 1 day) and 50 patients received BEAM (carmustine at 300 mg/m2 × 1 day, etoposide at 200 mg/m2 × 4 days, cytarabine at 2 × 200 mg/m2 × 4 days and melphalan at 140 mg/m2 × 1 day). The median age was 45 (18-73) years at the time of the diagnosis. No significant difference was observed in baseline characteristics between groups, including the disease control and previous therapies. Prior to high-dose chemotherapy, 79.4% of the patients were in complete remission (CR) and 20.6% was in partial remission (PR). With a median follow up of 30.5 months (range: 1-70 months) for the whole cohort, even though the OS was similar in both groups (86% ± 2.4 vs. 84% ± 3.2; p = 0.85), the PFS was noted to be superior among those who received conditioning with BEAM protocol (55% ± 3.7) compared to those with mitoxantrone-melphalan (30.6% ± 2.8; p = 0.006). In conclusion, we demonstrated that the BEAM regimen is an effective high-dose chemotherapy for lymphoma patients before AHSCT. Nevertheless mitoxantrone-melphalan regimen is also an alternative to the BEAM regimen.

Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic hematopoietic stem cell transplantation for acute leukemia patients: a single center experience.

Due to the high transplant related morbidity and mortality (TRM), relatively younger acute leukemia patients that have a good performance status and no comorbidity are eligible for myeloablative conditioning (MAC) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcomes of 84 consecutive adult patients with ALL (n=38) or AML (n=46) who underwent allo-HSCT from their HLA-identical siblings were evaluated retrospectively. The median age at transplantation was 34 (17-58 years) for the whole patient population. Of these, 24 patients received a MAC and 60 patients received a fludarabine-based reduced intensity conditioning regimen (RIC). After a median follow-up of 32 months (range, 1-119), for the entire group, the 3-year estimated overall survival (OS) was 57.5% and the disease-free survival (DFS) was 51.5%. The OS for ALL and AML patients were 53.9% vs 62.1%: and DFS were 50.5% and 53.4%, respectively. The 3-year estimated OS for RIC and MAC patients were 63.2% and 41.7%; and DFS were 57.1% and 34.7%, respectively. In ALL patients, conditioning regimens (RIC vs MAC) led to similar OS and DFS; however, in AML patients both OS (70.1% vs 21.4%) and DFS (59.3% vs 42.9%) were found to be higher in RIC patients compared to MAC recipients. Overall, the TRM at day 100 was 1.7% and has increased up to 5.1% at 1st year. In multivariate analysis, the diagnosis (p=0.03) and RIC regimen (p=0.027) were the prognostic variables for prolonged OS in all patients; and RIC regimen (p=0.031) was the only prognostic factor for prolonged OS in AML patients. The first complete remission (CR1) was correlated with a prolonged DFS as an independent variable for all patients (p=0.09). Eleven of the RIC patients (18.3%) and 6 of the MAC patients (25%) developed acute graft-versus-host disease (GvHD). Seventeen of the RIC patients (33.3%) and 4 of the MAC patients (16.7%) developed chronic GvHD. In conclusion, RIC conditioning regimens may provide a longer OS and DFS, especially in patients with AML who are in first CR, not eligible for MAC conditioning.

Hyper-CVAD regimen in routine management of adult acute lymphoblastic leukemia: a retrospective multicenter study.

Treatment of acute lymphoblastic leukemia is unsatisfactory in adults due to disease and patient-related factors and probably because adult chemotherapy regimens are weaker than pediatric protocols. Worries about inadequacy of adult regimens urged many hematologists, including us, to reconsider their routine treatment practices. In this retrospective multicenter study, we aimed to evaluate results of hyper-CVAD treatment in comparison to other intensive protocols. All patients aged ≤65 years who were commenced on intensive induction chemotherapy between 1999 and 2011 were included in the study. Sixty-eight of 166 patients received hyper-CVAD, 65 were treated with CALGB-8811 regimen and 33 with multiple other protocols. Limited number of patients who were treated with other intensive protocols and mature B-acute lymphoblastic leukemia cases who were mostly given hyper-CVAD were eliminated from the statistical analyses. In spite of a favorable complete remission rate (84.2%), overall (26.3 vs. 44.2% at 5 years, p = 0.05) and disease-free (24.9 vs. 48.2%, p = 0.001) survival rates were inferior with hyper-CVAD compared to CALGB-8811 due to higher cumulative nonrelapse mortality risk (29.7 vs. 5.9%, p = 0.003) and no superiority in cumulative relapse incidence comparison (45% for both arms, p = 0.44). Hyper-CVAD, in its original form, was a less favorable regimen in our practice.

A comparison of Jurkat cell-reactive anti-T lymphocyte globulin and fetal anti-thymocyte globulin preparations in the treatment of aplastic anemia.

OBJECTIVE: The aim of this study was to investigate the success rate and effects on survival of different anti-thymocyte globulin (ATG) preparations in patients diagnosed with aplastic anemia. SUBJECTS AND METHODS: Of the total 24 patients included in the study, 12 were male and 12 female with a median age of 44 years (range 16-72). Nine patients received Lymphoglobulin®, 7 Thymoglobulin® and ATG-Fresenius® (ATG-F). There was no significant difference between the three treatment groups in terms of severity of aplastic anemia. RESULTS: The estimated 6-month survival rates for ATG-F, Lymphoglobulin and Thymoglobulin groups were 42.9, 77.8 and 71.4%, respectively. The difference in overall survival rates between groups was not significant, most likely due to the low number of patients. The most striking result was that none of the patients in the ATG-F preparation group showed any response to treatment. The ATG-F group was found to have a significantly inferior response rate (p = 0.07). CONCLUSION: Our data showed that none of the patients responded to ATG-F treatment. Hence, despite the small number of the patients, we recommend that ATG-F should not be used for treatment of severe aplastic anemia.

Spinal myeloid sarcoma in two non-leukemic patients.

Myeloid sarcoma, formerly termed granulocytic sarcoma or chloroma, consists of neoplastic granulocytic precursors and myeloblasts. Isolated chloromas (granulocytic sarcomas) are rare tumors. Spinal complications of chloromas, such as cord compression secondary to epidural tumor or cauda equine syndrome have been described but are rare. We herein report two cases with spinal granulocytic sarcomas in non-leukemic patients. The case of a previously healthy 22-year-old man diagnosed with multiple spinal granulocytic sarcomas with no evidence of bone marrow or other hematological involvement is described. And, a 43-year-old woman diagnosed cervical spinal granulocytic sarcoma with no evidence of bone marrow or other hematological involvement is described. The tumor was totally removed by microsurgery. The histopathological examination was consistent with granulocytic sarcoma. Granulocytic sarcoma should be considered in the differential diagnosis of an epidural mass in patients with or without acute leukemia, because early diagnosis followed by appropriate combined chemotherapy and radiation may obviate surgical intervention and eventually prevent leukemic transformation.

Hypotension, Syncope, and Fever in Systemic Mastocytosis without Skin Infiltration and Rapid Response to Corticosteroid and Cyclosporin: A Case Report.

Mast cell disorders are defined by an abnormal accumulation of tissue mast cells in one or more organ systems. In systemic mastocytosis, at least one extracutaneous organ is involved by definition. Although, systemic mastocytosis usually represents with skin lesion called urticaria pigmentosa, in a small proportion, there is extracutaneous involvement without skin infiltration. Other manifestations are flushing, tachycardia, dyspepsia, diarrhea, hypotension, syncope, and rarely fever. Various medications have been used but there is not a definite cure for systemic mastocytosis. The principles of treatment include control of symptoms with measures aimed to decrease mast cell activation. We describe a case of systemic mastocytosis presenting with hypotension, syncope attacks, fever, and local flushing. In bone marrow biopsy, increased mast cell infiltration was demonstrated. She had no skin infiltration. A good clinicopathological response was obtained acutely with combination therapy of glucocorticoid and cyclosporine.

Identification of clinical and simple laboratory variables predicting responsible gastrointestinal lesions in patients with iron deficiency anemia.

Iron deficiency anemia (IDA) is a frequent disorder. Also, it may be a sign of underlying serious diseases. Iron deficiency points to an occult or frank bleeding lesion when occurred in men or postmenopausal women. In this study, we aimed to evaluate the diagnostic yield of endoscopy in patients with IDA and to define predictive factors of gastrointestinal (GI) lesions causing IDA. Ninety-one patients (77 women, 14 men; mean age: 43 years) who were decided to have esophago-duodenoscopy and/or colonoscopy for iron deficiency anemia were interviewed and responded to a questionnaire that included clinical and biochemical variables. The endoscopic findings were recorded as GI lesions causing IDA or not causing IDA. Endoscopy revealed a source of IDA in 18.6 % of cases. The risk factors for finding GI lesions causing IDA were as follows: male gender (p= 0.004), advanced age (> 50 years) (p= 0.010), weight loss (over 20% of total body weight lost in last 6 month) (p= 0.020), chronic diarrhea (p= 0.006), change of bowel habits (p= 0.043), epigastric tenderness (p= 0.037), raised carcinoembryonic antigen (CEA) level (normal range: 0-7 ng/mL) (p= 0.039), < 10 gr/dl hemoglobin (Hb) level (p=0.054). None of these risk factors had been present in 21 (23%) women younger than 51 years. In this group, no patient had any GI lesion likely to cause IDA (negative predictive value= 100%). In multivariate analysis, advanced age (p=0.017), male gender (p< 0.01) and weight lost (p=0.012) found that associated with GI lesions in all patients. It may be an appropriate clinical approach to consider these risk factors when deciding for gastrointestinal endoscopic evaluation in iron deficiency anemia.

Primary thyroid marginal zone B-cell lymphoma MALT-type in a patient with rheumatoid arthritis.

Autoimmune diseases are defined as specific, adapted immune reactions against self antigens. Immune mechanism deficiency is a causal factor for B-cell lymphoma in primary Sjögren's syndrome and autoimmune thyroid disease. Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a 67-fold and parotid lymphoma is a 44-fold increased risk in Sjögren's syndrome and thyroiditis. MALT lymphoma was not reported in rheumatoid arthritis. We herein report the case of a 56-year-old woman with maltoma of thyroid in rheumatoid arthritis patient.

Concomitant renal cell carcinoma and lymphoid malignancies: a case series of five patients and review of the literature.

Appearance of non-Hodgkin's lymphomas (NHL) and renal cell carcinoma (RCC) in same person has been reported in the literature. There is a higher-than-expected incidence of co-occurrence of these neoplastic disorders. The cause for this association remains speculative. Two epidemiological studies have shown that the observed-to-expected ratio for occurrence of RCC in NHL patients were 1.86 to 2.67. We herein describe five patients with both RCC and lymphoid malignancies, and reviewed possible explanations for the association. In three of the five patients, RCC was diagnosed during lymphoproliferative disease work-up, and remaining two cases had been diagnosed with chronic lymphocytic leukemia 1 and 5 years prior to RCC. All RCC cases were detected during staging of the primary tumor, usually by CT scan and/or ultrasound. Our data are in correlation with the literature that there is an increased association of RCC and NHL more often among male patients, and that the lymphoproliferative disease often presents with extranodal involvement. The specialists should be alerted for this possibility when evaluating patients at diagnosis or during follow-up.

Multiple bulky cutaneous plasmacytomas with CNS relapse without bone marrow involvement during the course of a lambda light chain myeloma.

BACKGROUND: Primary cutaneous plasmacytomas, a localized collection of neoplastic plasma cells, may present without bone marrow involvement. Secondary plasmacytomas can complicate the clinical course of multiple myeloma (MM). Both types of cutaneous plasmacytoma are commonly observed in the terminal stages of MM. CASE REPORT: We present the case of a 37-year-old Turkish man diagnosed with lambda light chain MM. The patient had numerous firm plaque-shaped cutaneous lesions on the left side of the chest, the left shoulder, and the right preauricular region without concurrent bone marrow disease. Histopathological examination of the cutaneous plaque on the left side of the chest revealed neoplastic plasma cells infiltrating the dermal region. Furthermore, the cytologic examination of cerebrospinal fluid disclosed lymphoplasmacytic cells. The patient was treated with VDTPACE (bortezomib + dexamethasone + thalidomide + adriamycin + cyclophosphamide + etoposide), and the cutaneous lesions disappeared. Central nervous system involvement was treated with craniospinal irradiation and intrathecal chemotherapy. CONCLUSION: Cutaneous involvement of MM is an unusual clinical presentation, but a high level of suspicion is advisable in patients with MM and skin lesions. The involvement of the skin was associated with advanced disease status and, therefore, with a poor prognosis. This is the first reported case of cutaneous involvement of lambda light chain MM.

Biphenotypic acute leukemia treated with acute myeloid leukemia regimens: a case series.

This study retrospectively analyzed 8 cases of biphenotypic acute leukemia (BAL) in respect of morphology, immune phenotype, karyotype, and clinical manifestations. Six patients had myeloid plus T lymphoid, and 2 cases had myeloid plus B-lymphoid immune phenotypic markers. Because selection of an antileukemic chemotherapy regimen for acute leukemia is largely based on whether a case is classified as myeloid or lymphoid, the presence of markers for both lineages may have important implications for treatment. However, there is no consensus yet on chemotherapy for patients with BAL. All of our patients were treated with regimens designed for acute myeloid leukemia (AML). Five patients were treated with high-dose cytarabine plus mitoxantrone and 3 achieved complete remission. Two patients treated with idarubicin plus cytarabine. Both of them achieved complete remission. One case was given cytarabine plus mitoxantrone and achieved complete remission. Consequently, 6 out of 8 BAL patients achieved complete remission with AML-type regimens.

Transformation of adult myelodysplastic syndrome-refractory anemia to acute T-cell lymphoblastic leukemia.

OBJECTIVE: Myelodysplastic syndrome (MDS) is recognized as a preleukemic disorder with a variable risk of transformation to acute myeloid leukemia. Usually the blast cells in leukemia are transformed after MDS displays a myeloid phenotype. Lymphoid progression had been reported as myeloid-lymphoid hybrid or early B phenotype, but our patient transformed acute T-lymphoblastic leukemia, which is a rare lymphoid transformation. CLINICAL PRESENTATION AND INTERVENTION: We present a case of refractory anemia with excess of blast that transformed into acute T-cell lymphoblastic leukemia. MDS was diagnosed in a 69-year-old man in April 2007. Twelve month later, he developed T-acute lymphoblastic leukemia. The blasts were positive for expression of CD2, CD3, CD5, CD7, CD45, and HLA-DR, leading to a diagnosis of T-lymphoblastic leukemia. The patient was treated with chemotherapy, but he died of multiple organ failure. CONCLUSION: The mechanism of lymphoid transformation is not yet fully understood. This case clinically supports the nature of MDS as a pluripotent hematopoietic stem cell disorder. MDS often transforms into acute leukemia, usually of a myeloid phenotype. The transformation of MDS into acute lymphoblastic leukemia is extremely rare.

Changes in vascular endothelial growth factor, angiopoietins, and Tie-2 levels with G-CSF stimulation in healthy donors.

The roles of vascular endothelial growth factor (VEGF), Tie-2, and angiopoietins in the mobilization of the hematopoietic stem cells (HSCs) in humans are not yet clearly understood. In order to elucidate mechanisms of HSC mobilization from their niches, we aimed to investigate the effects of mobilization with granulocyte colony-stimulating factor to the levels of VEGF, Tie-2, and angiopoietins 1 and 2 in the allogeneic HSC transplantation donors. Soluble VEGF, Tie-2, angiopoietin 1 and angiopoietin 2 levels were studied in 20 healthy allogeneic HSC transplantation donors before (from peripheral blood) and 5 days after mobilization (from apheresis material). Mean VEGF level in the postmobilization apheresis sample was significantly higher compared to baseline premobilization peripheral blood (t test, p < 0.001). In contrast, mean Tie-2 level in the postmobilization aphaeresis sample was significantly lower compared to baseline premobilization peripheral blood (t test, p = 0.01). Angiopoietin 1 and angiopoietin 2 levels did not differ between baseline and postmobilization samples. A significant rise in VEGF level after mobilization suggests stimulation of the angiogenesis. A significant fall in Tie-2 level suggests suppression of the angiopoietin 1/Tie-2 signaling, leading to release of HSC from the hematopoietic niches and mobilization to the peripheral blood.

Septic pulmonary embolism secondary to dental focus.

A 24-year-old female was admitted to an infectious diseases unit with complaints of dyspnea and fever. She had suffered from multiple episodes of fever for 1 year. The diagnostic workup revealed multiple pulmonary nodules on the chest CT scan, suggesting septic pulmonary embolism, and a periapical abscess around the maxillary right central incisor. Because no other infectious source was found and resolution of the fever and the pulmonary lesions occurred only after extraction of the affected tooth and antibiotic therapy, the condition was diagnosed as a periapical abscess complicated by septic pulmonary embolism.

Measuring holotranscobalamin II, an early indicator of negative vitamin B12 balance, by radioimmunoassay in patients with ischemic cerebrovascular disease.

Circulating homocysteine is a risk factor of cardiovascular and cerebrovascular events. Hyperhomocysteinemia may be an early indicator for vitamin B12 disorders because cobalamin is a cofactor in the remethylation process of homocysteine. Serum holotranscobalamin (holoTC II) becomes decreased before the development of metabolic dysfunction. In this study, we assessed circulating holoTC II to estimate the diagnosis of vitamin B12 deficiency in the first ischemic cerebrovascular attack. We also compared the efficacy of the measurement of plasma holoTC II with the other standard biochemical and hematological markers used to reach the diagnosis of cobalamin deficiency. Forty-five patients (age 71 years (range 35-90), 16 men/29 women) within the first ischemic cerebrovascular event were included in this prospective study. All the enrolled patients have been administered vitamin B12 1 mg intramuscular injection once a day for 10 days. At the baseline and on the tenth day of treatment, plasma levels of holoTC II and the proper biochemical and hematological markers in diagnosing cobalamin deficiency were measured. After admission, anemia and diminished serum vitamin B12 levels were determined to be only 20% (9/45) and 44% (20/45), respectively; 78% (35/45) of the patients had low serum holoTC II (<37 pmol/l). Serum homocysteine was higher in patients (49% of them) who had previously suffered a stroke. Thrombocytopenia, hypersegmentated neutrophils, and indirect hyperbilirubinemia were observed in 20% of the patients. Leukopenia and macrocytosis were not evident in any of them. In 18 of 27 patients (67%) that had low holoTC II levels after joining the study and who remained in the study until the end of cobalamin treatment, serum holoTC II levels returned to normal values. Cobalamin deficiency should be considered in patients with cerebrovascular diseases, even if anemia, elevated mean cell volume, depression of the serum cobalamin, or other classic hematological and/or biochemical abnormalities are lacking. Furthermore, measurement of serum holoTC II looks promising as a first-line of tests for diagnosing early vitamin B12 deficiency.