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Anca Bacârea, Claudia Bănescu, Ioan Macarie, Judit Beáta Köpeczi and Bogdana Dorcioman

Abstract

Very few cases of chronic lymphocytic leukemia (CLL) presenting with extreme hyperleukocytosis are reported in the literature. We describe the case of a 66 years old woman, with newly diagnosed CLL presenting with extreme hyperleukocytosis of 774.2 x 109/liter, Rai stage III and Binet stage C. The patient has no comorbidities and the CIRS score (cumulative illness rating scale) is well below 6, with normal creatinine clearance. Some other interesting aspects related with this case are the atypical immunophenotype, the expression of Cyclin D1, and the B hepatitis viral infection, which made her diagnosis and treatment challenging. The patient was tested for NOTCH1 mutation and it was positive. There is important evidence that NOTCH1 mutations are associated with rapidly progressive disease and resistance to treatment. The distinction of CLL from mantle cell lymphoma (MCL) is not always easy because some MCLs may mimic CLL clinically, histologically, and/or phenotypically. The hepatitis B prophylaxis for viral reactivation was not available an in the end the patient was treated only with fludarabine and cyclophosphamide, without rituximab. CD200 should be introduced in the routine panel for flow cytometry to distinguish CLL from mantle cell lymphoma and NOTCH1 mutation is associated with poor prognosis and should be evaluated at diagnosis. CLL with extreme hyperleukocytosis presentation is very rare and sometimes an atypical CLL may represent a diagnostic pitfall.

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

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

Szende Jakab, Erzsébet Lázár, István Benedek, Judit Beáta Köpeczi, Annamária Pakucs and István Benedek

Abstract

Multiple myeloma accounts for 10% of the hematologic malignancies and is characterized by a single clone of plasma cells producing a monoclonal protein. The aim of this review is to summarize the current treatment methods of multiple myeloma. In the last 15 years, the incidence of myeloma has increased in patients younger than 65 years, thus treatment became even more important in order to obtain a long lasting remission or plateau phase. The treatment of this disease is complex and focuses not only on increasing the patients’ survival, but also improving their quality of life.

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

István Benedek, Erzsébet Lázár, Judit Beáta Köpeczi, István Benedek, Aliz Beáta Tunyogi, Szende Jakab and Annamária Pakucs

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder, which can involve the hematopoietic stem cell or early progenitor cells, without the loss of their capacity to differentiate. Typically, CML has three clinical phases: a chronic phase, an accelerated phase, and an aggressive transformation in blast crisis, analogous to acute leukemia. The following article presents the case of a 49-year-old patient diagnosed with Philadelphia-negative CML in blastic transformation, where after multiple conventional acute leukemia induction chemotherapy regimens an unrelated allogeneic hematopoietic stem cell transplant was performed.

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

István Benedek, István Benedek, Judit Beáta Köpeczi, Johanna Sándor Kéri, Annamária Pakucs, Szende Jakab and Erzsébet Lázár

Abstract

Plasma cell leukemia (PCL) is one of the most aggressive monoclonal gammopathies, being characterized by the presence of more than 20% of plasma cells in the peripheral blood and an absolute number of these cells of more than 2×109, with different morphology, from young elements to mature cells. The incidence of PCL varies between 2–4% among multiple myeloma (MM) patients. In comparison with MM, PCL appears more often in younger patients. The following article describes the case of a 49-year-old female patient diagnosed with PCL which needed urgent control of the clinical manifestations due to its irreversible complications. Urgent autologous stem cell transplantation is recommended in this group of patients.

Open access

István Benedek, Erzsébet Lázár, Annamária Pakucs, Judit-Beáta Köpeczi, István Benedek, Szende Jakab and Johanna Sándor-Kéri

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), representing up to 30 percent of all lymphomas. DLBCL is a fast-growing, aggressive form of NHL, which can appear as a transformation from a less aggressive form of lymphoma or can be de novo pathology. The following article describes the case of a 55-year-old female patient who developed a DLBCL as a second malignancy after an R-CHOP-treated marginal zone splenic lymphoma. This was followed by the transformation of the DLBCL into an aggressive acute lymphoblastic leukemia, for which the patient needed aggressive treatment according to the international acute lymphoblastic leukemia protocol.

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.