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Judit Beáta Köpeczi, Erzsébet Benedek, Enikő Kakucs, Aliz Tunyogi, Monica Istrati and Istvan Benedek

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), recently classified among the acute myeloid leukemia and related precursor neoplasms, is a rare hematological malignancy with highly aggressive clinical course. We report a case of a 55 year-old female patient who presented spontaneous rupture of the spleen. The histopathological diagnosis without immunohistochemistry was splenic marginal zone non-Hodgkin lymphoma (NHL). The patient received 4 courses of polychemotherapy. Due to the unfavorable evolution the spleen was histopathologically reexamined and immunohistochemistry was performed in another laboratory. The diagnosis of NHL was excluded. Undifferentiated malignant cell proliferation, possible myeloid was suspected. Due to the discrepancy between diagnoses, a third immunohistological examination was performed in a third laboratory. NHL was excluded and myeloid, NK-cell or plasmacytoid dendritic cell leukemia was suspected. The patient was admitted to our clinic after 8 months from the initial diagnosis. Immunophenotyping by flowcytometry from the bone marrow showed 23% blasts positive for CD4, CD56, CD123, HLA-DR, CD38, CD11b, CD2, and negative for lineage specific markers of B-, T-lymphoid, NK- or myelomonocytic cells. The final diagnosis was BPDCN in leukemic phase. Due to the diversity of the clinical presentation, morphology and immunophenotype of BPDCN the diagnosis of this rare malignancy remains challenging. Immunophenotyping by flowcytometry is superior to immunohistochemistry because of the availability of a larger panel of antibodies and the possibility to identify the intensity of antigen expression. The atypical forms of BPDCN should be recognized early in order to manage properly the patients with this aggressive disease

Open access

Enikő Kakucs, I Benedek, Erzsébet Benedek, Judit Beáta Köpeczi, Aliz Tunyogi and Monica Istrati

Abstract

Introduction: Autologous haemopoietic stem cell transplantation (SCT) is an important treatment modality for patients with acute myeloid leukemia with low and intermediate risk disease. It has served advantages over allogenic transplantation, because it does not need a matched donor, there is no graft versus host disease, there are less complications and a faster immune reconstitution than in the allo-setting. The disadvantage is the lack of the graft versus leukaemia effect.

Materials and methods: In the Bone Marrow Transplantation Unit Tîrgu Mureș 14 patients with acute myeloid leukemia received an autologous SCT. Mobilization of the stem cells was performed using chemotherapy and granulocytic colony stimulating factor. The conditioning regimen for SCT consists in monotherapy with busulfan (Bu) 16 mg/kg, BuCy: busulfan in combination with Cyclophosphamide (CY) 120 mg/ kg or BuMel: Busulfan in association with Melphalan (Mel) 140 mg/m2.

Results: The median patient age was 36 years (range 20-55), 9 (64%) were males and 5 (36) were females and the median time interval from diagnosis to autologous SCT was 9 months (range 3-25). All the patients were transplanted successfully, all of them achieved a sustained neutrophil count (> 0.5 G/L), median time 11 days (9-15) and platelet count (> 20 G/L) median time 14 days (10-19) after transplantation.

Conclusions: We conclude that autologous stem cell transplantation is an effective treatment in acute myeloid leukemia with the possibility of long survival, particularly in patients with standard risk disease

Open access

Aliz-Beáta Tunyogi, I Benedek, Judit Beáta Köpeczi, Erzsébet Benedek, Enikő Kakucs, Monica Istrati and Zsuzsa Pap

Abstract

Introduction: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder; the molecular hallmark of the disease is the BCR-ABL gene rearrangement, which usually occurs as the result of a reciprocal translocation between chromosomes 9 and 22. Tyrosine kinase inhibitors (TKI) were the first drugs that targeted the constitutively active BCR-ABL kinase and it have become the standard frontline therapy for CML. Monitoring the treatment of CML patients with detection of bcr-abl transcript levels with real time qualitative polymerase chain reaction (RQ-PCR) is essential in evaluating the therapeutic response.

Material and method: At the Clinical Hematology and BMT Unit Tîrgu Mureș, between 2008-2011, we performed the molecular monitoring of bcr-abl transcript levels with RQ-PCR in 16 patients diagnosed with CML.

Results: We have 11 patients on imatinib treatment who achieved major molecular response. One patient lost the complete molecular response after 5 years of treatment. Two patients in blast crisis underwent allogeneic hematopoietic stem cell transplantation from identical sibling donors. The first patient is in complete molecular remission after 4 years of the transplant with mild chronic GVHD. The other patient had an early relapse with treatment refractory disease and died from evolution of the disease. Three patients with advanced phases of the disease present increasing transcript levels. We performed the dose escalation, and for two of them the switch to the second generation of TKI.

Conclusions: Regular molecular monitoring of individual patients with CML is clearly desirable. It allows for a reassessment of the therapeutic strategy in cases of rising levels of BCR-ABL as an early indication of loss of response.

Open access

Eszter Mild, Erzsébet Lázár, Judit-Beáta Köpeczi, Enikő Kakucs, Marius Găzdac, Annamária Pakucs, Cezara Tudor and István Benedek

Abstract

Background: High-dose chemotherapy and autologous stem cell transplantation have become a standard curative treatment in various hematologic malignancies. Many factors can affect the success of mobilization and hematopoietic stem cell harvesting.

Aim: The aim of this study was to analyze factors that lead to mobilization failure.

Material and Methods: We conducted a retrospective study on 19 patients with failure of stem cell harvesting. All patients were administered high doses of GCS-F (filgrastim, 15 μg/kg/day) and 0.24 mg/kg of plerixafor on day +5 or +10 of harvesting.

Results: The median age of the study population was 51 years (range 35–67) and 52.6% (n = 10) were males. The study group included 4 (21%) subjects with multiple myeloma, 6 (31.5%) with Hodgkin lymphoma, 8 cases (42.1%) with non-Hodgkin lymphoma and 1 patient with chronic lymphocytic leukemia. Each patient received 2.78 (range 1–5) lines of chemotherapy, administered in 11.57 (range 2 to over 20) cycles of treatment.

Conclusion: In hematologic malignancies it is very important to collect stem cells in time, in order to reduce mobilization failure. As we have shown in our studied cases, multiple lines of polychemotherapy with or without radiotherapy lead to mobilization failure.

Open access

Aranka Kurtus, Erzsébet Benedek, Judith Beáta Köpeczi, Enikő Kakucs, Aliz-Beáta Tunyogi, Monica Istrati and I Benedek

Abstract

Introduction: Anemia is a common complication of malignant lymphomas, which could be a direct consequence of the disease or secondary to the myelosupressive chemotherapy. The aim of this study was to assess the effect of erythropoietin to treat anemia. The main objectives were to demonstrate increases in hemoglobin levels and the existence of an association between symptom relief and treatment.

Material and method: In the Clinical Hematology and BMT Unit Tîrgu Mureș we performed an analytical, observational study to assess the role of erythropoietin treatment in malignant lymphoma related anemia. This linear, retrospective study included 127 patients diagnosed and treated with malignant lymphoma between January 1st, 2007 and December 30, 2011. The 127 patients were divided into two groups: a group of patients (n = 88) who were treated with erythropoietin and the other group (n = 39) who did not receive this treatment. Patients included in the study received treatment with epoetin beta 40,000 IU/week. We followed the hemoglobin level and the symptomatology at baseline and after 4 weeks.

Results: Patients who received treatment with erythropoietin had a 7.12 times higher possibility of being asymptomatic than patients who did not receive this treatment. The hemoglobin concentration of patients with erythropoietin treatment increased significantly (p <0.0001) compared to the patients who did not receive this treatment.

Conclusion: Effective treatment of anemia is an important aim in the management of patients with malignant lymphomas, because it increases their hemoglobin concentration, decreases the need of transfusion and maintains an acceptable quality of life.

Open access

István Benedek, Judit-Beáta Köpeczi, Enikő Kakucs, Szende Jakab, István Benedek and Erzsébet Lázár

Abstract

We present the method of immunomagnetic stem cell separation with the ISOLEX 300i device (Isolex® 300i Magnetic Cell Selection System, Nextell Therapeutics Inc. Irvine California 21618 USA) and the results obtained using this method in patients admitted to the Hematology and Bone Marrow Transplantation Clinic of Tîrgu Mureş, Romania. Cell selection has a great importance in separating stem cells from tumor cells, therefore contributing to the success of autologous stem cell transplantation.

Open access

Judit Beáta Köpeczi, I Benedek, Erzsébet Benedek, Enikő Kakucs, Aliz Tunyogi, Monica Istrati and Aranka Kurtus

Abstract

Introduction: Plasmacytoid dendritic cell leukemia is a rare subtype of acute leukemia, which has recently been established as a distinct pathologic entity that typically follows a highly aggressive clinical course in adults. The aim of this report is to present a case of plasmacytoid dendritic cell leukemia due to its rarity and difficulty to recognize and diagnose it.

Case report: We present a case of a 67 year-old man who presented multiple subcutaneous lesions on his face, neck, chest and upper extremities with reddish-brown, brown colour. In the bone marrow aspirate 83% of the blast cells were found. Immunophenotypically the blasts were positive for CD4, CD56, CD123 (high intensity), CD36, CD22, CD10 (10.42%), CD33, HLA-DR, CD7 (9.24%), CD38 (34.8%) and negative for CD13, CD64, CD14, CD16, CD15, CD11b, CD11c, CD3, CD5, CD2, CD8, CD19, CD20, CD34. The skin biopsy showed lymphohistiocytoid infiltration in the dermis. The patient was diagnosed with acute plasmacytoid dendritic cell leukemia and received polychemotherapy with rapid response of skin lesions and blastic infiltration of the bone marrow. After 3 courses of polychemotherapy the cutaneous lesions reappeared and multiplied. The blast infiltration in the bone marrow increased to 70%. A more aggressive polychemotherapy regimen was administered, but the patient presented serious complications (febrile neutropenia) and died in septic shock 8 months after the initiation of treatment.

Conclusions: Immunophenotyping of blasts cells is indispensable in the diagnosis of plasmacytoid dendritic cell leukemia. The CD4+, CD56+, lin-, CD123 ++high, CD11c-, CD36+, HLA-DR+, CD34-, CD45+ low profile is highly suggestive for pDCL. The outcome of plasmacytoid dendritic cell leukemia is poor. Despite the high rate of initial response to treatment, early relapses occur and the patients die of disease progression.

Open access

Erzsébet Benedek Lázár, Judit Beáta Köpeczi, Aliz Beáta Tunyogi, Enikő Kakucs, Alina Cătană and I Benedek

Abstract

Background: There are several histologic variants and clinical subtypes of diffuse large B cell lymphoma, which includes the primary mediastinal large B cell lymphoma (PMBL). In the last 10 years the incidence of diffuse large lymphomas grew significantly.

Case report: We present the case and evolution of an aggressive life-threatening mediastinal B cell lymphoma with respiratory insufficiency, diagnosed in the 27th week of pregnancy. After 4 courses of R-CHOP the clinical status has somewhat improved, but the dyspnea, the facial and neck oedema and the trouble of speech persisted. After the patient was admitted to our hospital, she received DHAP regimen followed by mobilization with G-CSF. Before transplantation we administered another 3 courses of DHAP chemotherapy with spectacular results. We performed autologous hematopoietic stem cell transplantation preceded by BEAM chemotherapy. At present, 5 years post-transplant the patient is well, with no metabolically active disease on the PET-CT performed 3 months ago.

Conclusion: We can conclude that even in very complicated DLBCL cases, with a very good, efficient medical-team work we can salvage lives, in our case both of the mother and the child’s. Even in partially chemo-refractory cases like in the presented one, salvage chemotherapy followed by autologous transplantation can lead to a successful treatment.

Open access

Erzsébet Lázár, Judit-Beáta Köpeczi, Enikő Kakucs, István Benedek, Szende Jakab, Annamária Pakucs, Cezara Tudor and István Benedek

Abstract

This study presents a new method of combined growth factor mobilization with increased dose (15 μg/kg) of filgrastim and standard mono dose of plerixafor in subjects with multiple myeloma, Hodgkin or non-Hodgkin lymphoma. Efficient mobilization is a key factor in the treatment of this group of patients, because autologous transplantation can be performed in cases in which we succeed to obtain a minimally sufficient number of stem cells. Autologous stem cell transplantation is included in the current standard treatment of multiple myeloma and in the relapsed cases of lymphomas.

Open access

Annamária Pakucs, Erzsébet Lázár, Judit Beáta Köpeczi, Enikő Kakucs, István Benedek, Marius Găzdac, Eszter Mild, Cezara Tudor and István Benedek

Abstract

Introduction: Autologous hematopoietic stem cell transplantation (ASCT) represents a standard therapy in the management of hematologic malignancies such as malignant lymphomas and has used for approximately three decades. The aim of this study was to determine the occurring post-ASCT complications and their impact on the patients’ recovery for a better management.

Material and methods: An observational retrospective study was performed during a five-year period between 2012 and 2017, involving 58 classical Hodgkin lymphoma and 36 non-Hodgkin lymphoma patients, who underwent ASCT in the Bone Marrow Transplantation Unit of Tîrgu Mureş. The main analyzed complications were: infections, bleeding, hydroelectrolytic disorders, and hypoalbuminemia.

Results: After data analysis we found that 17 patients (18%) presented microbiologically confirmed infection, 10 patients (11%) presented clinically non-significant bleeding, 39 patients (42%) presented electrolyte disorders, and 33 patients (36%) presented hypoalbuminemia, obtaining a positive correlation between the rate of adverse events after ASCT with age (r = 0.9914, p = 0.0009) and the average hospitalization period (r = 1, p <0.00001).

Conclusions: The identification of adverse events and their correlation with the patients’ clinical outcome can lead to better patient management and a faster recovery after ASCT.