Journal of Blood & Lymph

Patients diagnosed with chronic lymphocytic leukemia (CLL) do not necessarily have to undergo intensive treatment. The implementation of the therapy depends on patient condition and the form of CLL which is determined using predictive and prognostic factors. Both indolent and aggressive forms of CLL should be monitored. To improve survival and the quality of life it is very important to know how the organism responds to the treatment. For this purpose, the estimation of the minimal residual disease (MRD) - the pool of persistent leukemia cells after or at the time of treatment was introduced. These cells resistant to treatment can lead to recurrence of the disease. There are several methods for MRD assessment, however in every case it is necessary to know the initial status of the tested alterations (chromosome aberrations, surface protein expression, etc.). It allows for assessment whether the treatment eliminated the leukemic cells. The most common method for MRD evaluation in CLL is flow cytometry. Intensive development of molecular biology techniques can contribute to implementation of other extremely sensitive and specific methods. This review presents the most recent state of the art concerning minimal residual disease in CLL, including methods that are used for MRD assessment.

Introduction: 30% of patients with critical limb ischaemia (CLI) are not suitable for conventional treatment. Use of stem cell therapy (SCT) is relatively new. This study shares an initial experience using SCT in 4 patients. Methods: Approval from Institutional Medical Board Ethics Committee was obtained prior to commencement and informed consent was sought. Patients included had extensive CLI history that was no longer amenable to standard treatment. Bone marrow aspiration from the iliac crest was carried out under regional anaesthesia. This was later centrifuged and injected intramuscularly and adjacent to affected vessels. Wound surveillance was then performed. Results: SCT was well tolerated in all 4 patients and 2 had favourable results. None developed related complications. Patients 1 and 2 showed improvement of rest pain, claudication symptoms and healing of ulcers. Angiogenesis and neovascularization can be seen in follow up angiography for patient 1. Wound healing was not noted in the other 2 patients, with both requiring amputations eventually. Discussion: The experience while early has been invaluable. The varied response suggests that factors determining treatment success remained unknown. Likewise, most other trials have consisted of small uncontrolled patient series, with few randomized studies. Haemodialysis, diabetes mellitus and coronary arterial disease factors seemed to negatively affect angiogenesis. Severity of rest pain and number of repeated interventions, in particular bypass procedures, may negatively intervene with neo-capillary formation. SCT may eventually provide hope to patients and physicians. More research can help determine a specific group of patients that will benefit most.

Heart failure (HF) is considered a leading cause of death in patients with established cardiovascular (CV) and metabolic diseases. Although current treatment strategy has improved survival rate and clinical outcomes of HF, the HF prevalence exhibits growth especially in older patients’ population and survivors after coronary atherothrombotic events. Current clinical guidelines regarding treatment and prevention of HF claim the role of biological markers as pretty easy and powerful tool for diagnosis, risk stratification, and prognostication of HF. However, there is not clear whether all these biological markers are able to equally predict CV death and HF-related outcomes in patients with acute and chronic HF as well as in various phenotypes of HF. The aim of the review is to discuss a role of in risk stratification and individual treatment in patients with different phenotypes of HF.

TAFRO syndrome is a systemic inflammatory disorder characterized by a constellation of symptoms; thrombocytopenia with reticulin fibrosis of bone marrow, anasarca including pleural effusion and ascites, fever, renal dysfunction, and organomegaly (hepatosplenomegaly and lymphadenopathy). Although several histopathological features of TAFRO syndrome resemble those of mixed type of multicentric Castleman disease (MCD), some cases of TAFRO syndrome don’t show any significant lymphadenopathy. In addition, several clinical and laboratory findings of TAFRO syndrome are different from those of MCD. The onset and clinical course of TAFRO syndrome may be acute or subacute, sometimes fetal, but its etiology, pathogenesis and specific marker is undetermined. Some patients have been successfully treated with corticosteroids, immunesuppressants including cyclosporine A, tocilizumab or rituximab, whereas others were refractory to treatment and succumbed to the disease. For contribution to the prompt diagnosis and appropriate treatment of TAFRO syndrome, the research team has defined its preliminary diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome. To promote the research on TAFRO syndrome, multicenter retrospective clinical study in Japan has been performed, and prospective study is being designed by a nation-wide research team on TAFRO syndrome.

Ibrutinib is an oral Bruton’s tyrosine kinase inhibitor with clinical efficacy in several B cell malignancies. In a pooled analysis of clinical trials evaluating ibrutinib, grade 3-4 infections were reported in 14% of patients. We screened consecutive patients on ibrutinib therapy for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) for infectious complications. Patients were hospitalized with documented infections uncommon to this patient population including Legionella pneumonia, Campylobacter bacteremia and fatal progressive multifocal leukoencephalopathy (PML). All patients received prior therapies for CLL/MCL. Immunological evaluation of these patients demonstrated immunoglobulin depression and profound lymphopenia with severe depletion in both B and CD4 T cell counts, suggesting defects in both humoral and T cell mediated immunity. This data support a broader immunosuppressive effect for ibrutinib than initially anticipated. While responding patients may show later recovery of B cell function, profound immunosuppression may occur at earlier treatment time points, particularly in previously treated patients. Closer patient monitoring during the first months of ibrutinib therapy may be desirable.

Lymphoma is a type of cancer that causes the proliferation of B or T cells in lymph nodes. Lymphomas can be characterized in Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL), which account for about 85% of lymphoma diagnoses. The Immune System (IS) has the innate ability to identify and eliminate cells with tumor potential. Despite this, our body sometimes can’t combat this type of pathologies alone due to the mechanisms of tumor escape. T cells, which are very important cells in antitumor activity, have been studied and some trials show that the use of CAR-T cells may present an added value for the treatment of this type of pathologies. The CAR-T cells are genetically modified T lymphocytes to express the specific antibody binding site, directing autologus polyclonal T cells to bind to a specific Tumor Associated Antigen (TAA). The design and structure of CAR-T are determinant factors in the success of therapy. Four generations of Chimaeric Antigen Receptors (CARs) are known and the difference between they is in their signaling and costimulatory domains, such as CD28 or CD137 (4-1BB). Recent studies show effectiveness in certain cases of patients diagnosed with NHL and it is recognized that the combination of complementary immunotherapy enhances the effect of CAR-T cell therapy. There is still a need to find out which the most appropriate design and which is the ideal dose to maximize efficacy and reduce the toxicity of this therapy.

Aims: There were frequent hematogenous metastases ending with death due to brain metastasis in gestational choriocarcinoma (Ch-Ca) before methotrexate (MTX) therapy around 1960. As the gestational Ch-Ca was a systemic disease, it should be treated by systemic primary chemotherapy before local treatment. Methods: MTX was administered associating Actinomycin D, with intermittent or continuous regimen until the disappearance of Ch-Ca tumor and human chorionic gonadotropin (hCG). Results: Metastases, primary uterine focus, and hCG disappeared by the chemotherapy. Reproductive function recovered achieving normal uterine pregnancy after complete remission. Ch-Ca brain metastasis was treated by the MTX chemotherapy without recurrence for 20 years. Prevention of Ch-Ca: MTX was administered to 107 women after the complete hydatidiform mole until negative pregnancy test, where no Ch-Ca developed, while 6 Ch-Ca developed in 81 control cases of no MTX in 1968. An UICC RCT result was the same as above. However, 13 Ch-Cas were reported in 22 Japanese districts 2013, maybe no molar cyst was detected with B-mode image in early pregnancy, followed by no chemotherapy, but would be terminated as blighted ovum. The author calculated the number of estimated Ch-Ca cases to be 13, which was the same as actually reported number of Ch-Ca cases in 2013 and 2014.

Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem cells. It can also be secondary to other blood system diseases such as myelodysplastic syndromes (MDS) and myeloproliferative tumors neoplasms (MPN). The JAK2 V617F mutation has been reported in MPN, but rarely reported in patients with AML. This report is related a 60-year-old patient who suffered from AML with JAK2 V617F mutation. The platelet count was 603 × 109/L at onset. He was given the DA regimen for induction chemotherapy and received complete remission. But the regimen was forced to stop due to acute cerebral infarction after second HDA regimen consolidation chemotherapy. Six months later, the patient had a recurrence. No complete remission was achieved after repeated chemotherapy. At the same time, the patient was given aspirin for antiplatelet aggregation and interferon to reduce platelets, but he stopped using interferon because of the severe infection. Later the patient presented with acute cerebral infarction again. This is a rare case report indicating that the patient with JAK2 V617F mutation had a poor prognosis and had recurrent thrombotic diseases because of elevated platelets.

Background: Highly active anti-retroviral therapy (HAART) has brought significant change in reducing morbidity and mortality among children living with HIV/AIDS. Decisions concerning initiation and/or shifting of antiretroviral therapy (ART) are guided by monitoring the laboratory parameters of plasma HIV RNA (viral load) and CD4+ T cell count in addition to the patient’s over all clinical response. The demonstrations of the prognostic value of the CD4 cell count was of major importance in the development of therapeutic strategies. Therefore, the objective of this study was to assess factors predicting suboptimal CD4 cell recovery during first six months of ART. Methods: The study is retrospective cross sectional study to assess factors predicting suboptimal CD4 cell recovery. Medical records of patients’ were retrieved and important variables are captured to standard questionnaire tool. T-test is used to assess changes in CD4 cell count after initiation of ART. Binary logistic and multiple regressions were used to assess factors predicting CD4 cell recovery. Results: Data of 360 children were analyzed. CD4 cell count at the start of HAART ranged from 3-2003 cell/mL with an interquartile range of 231-317 cell/mL. After 6 months of HAART, the CD4 cell count has increased ranging from 71-2300 cell/mL with inter quartile range of 458-612 cell/mL and mean CD4 cell count difference of 230, 95%CI (199.414-260.613); P<0.001. Advanced clinical stage of the disease, severe degree of immunosupression, presence of anemia, presence of chronic diarrhea at base line, poor weight gain during first six months of HAART adversely affect the trends of CD4 recovery. Conclusion: Our study demonstrated that advanced clinical stage of the disease, severe degree of immunosupression, presence of anemia at baseline and presence of chronic diarrhea, poor weight gain during first six months of HAART were factors adversely affect the trends of CD4 recovery.