Effect of Blood Groups on Clinical Presentations and Treatment Outcomes in Immune Thrombotic Thrombocytopenic Purpura Patients with Severe ADAMTS13 Deficiency: A Multi-Center Experience.

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by accumulation of ultra-large von Willebrand factor (vWF) due to the significantly reduced activity ADAMTS13. Limited studies have been published examining the blood group as an epidemiological factor that can contribute to development of TTP. It has been suggested that due to low vWF levels, the distribution of the "O" blood group among TTP patients may be lower than anticipated compared to the blood group distribution rates in the normal population. The aim of this study was to explore the relationship between blood groups and the clinical outcome of immune TTP (iTTP). Methods: Thirty patients with iTTP with severe ADAMTS13 deficiency were enrolled. Data collection commenced in January 2011 and was completed by June 2020. It was analyzed whether there was a difference between the blood groups in terms of frequency of iTTP, response to treatment, frequency of relapse, and clinical and laboratory results. Results and Conclusions: The distribution of group "A" among patients with iTTP was higher than expected. Although not statistically significant, patients with blood group "O" required more TPE for the treatment and relapse rate was statistically higher than other blood groups. Mortality rate in all patients was 6.7%. Although blood group "A" is a risk factor for iTTP, the frequency of relapse is higher in the blood group "O."

Vitreous hemorrhage: A rare ophthalmic adverse effect due to imatinib treatment.

INTRODUCTION: Imatinib is generally well tolerated by patients. The most common ophthalmic side effects are eyelid edema and periorbital edema. Other side effects which occur at rates of <1% include blepharitis, blurred vision, conjunctival hemorrhage, conjunctivitis, retinal hemorrhage, etc. An uncommon case is here reported of a 51-year-old male with chronic myeloid leukemia who developed vitreous hemorrhage due to imatinib after 9 months of treatment. CASE REPORT: A 51-year-old male with leukocytosis detected in the blood test examination was referred to the Hematology Department. The bone marrow biopsy result was compatible with chronic myeloid leukemia. Imatinib treatment (400 mg/day) was started. In the ninth month of imatinib treatment, the patient complained of a sudden decrease in vision. Vitreous hemorrhage was detected in the left eye and the patient underwent surgery. Vitreous hemorrhage recurred 1 month after the operation. On the fourth day after the discontinuation of imatinib treatment, the patient's ophthalmic complaints improved significantly. The Naranjo algorithm was applied and a score of 9 was detected. The vitreous hemorrhage of the patient was attributed to imatinib, and so the treatment of the patient was switched to bosutinib. DISCUSSION: Imatinib is an oral signal inhibitor that targets tyrosine kinase for BCR/ABL, platelet-derived growth factor, stem cell factor, and c-kit (CD117). The conjunctiva and sclera have a large amount of c-kit positive mast cells which are inhibited by imatinib. The inhibition of c-kit positive mast cells by imatinib may be responsible for further exposure of the conjunctival mucosa to injuries.

Leukocytoclastic vasculitis due to ruxolitinib treatment: A rare adverse effect.

WHAT IS KNOWN AND OBJECTIVE: Primary myelofibrosis (PMF) is characterized by myeloid cell proliferation and prominent bone marrow fibrosis. Ruxolitinib, a selective inhibitor of JAK 1 and 2, significantly reduces constitutional symptoms and spleen size compared with placebo, and has significant clinical benefits in patients with myelofibrosis. The most common haematological side effects are thrombocytopenia and anaemia, and the most common non-haematological side effects are grade 1-2 diarrhoea and pyrexia. Leukocytoclastic vasculitis is small vessel vasculitis, characterized histopathologically by immune complex-mediated vasculitis of the dermal capillaries and venules in the lower extremities, which can be seen as palpable purpura. Although the cause is 50% idiopathic, the aetiology of leukocytoclastic vasculitis can be collected under many headings. CASE SUMMARY: The case is here presented of a patient with PMF who developed leukocytoclastic vasculitis after ruxolitinib treatment. Ruxolitinib was discontinued as the lesions were thought to be drug-related and all skin lesions disappeared approximately 2 months after termination of the drug. When the ruxolitinib treatment was restarted at the same dose (2 × 15 mg), the skin lesions recurred. The drug dose was reduced to 1 × 15 mg, and the rashes disappeared. Currently, the patient has no active complaints and is being followed up with ruxolitinib 1 × 15 mg without any complications. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, leukocytoclastic vasculitis due to ruxolitinib is extremely uncommon. This case report can be considered to contribute to the literature of this rare event.

Hypercalcemia associated with the interaction between all trans retinoic acid and posaconazole in an acute promyelocytic leukemia case.

INTRODUCTION: All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole. CASE REPORT: A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole. MANAGEMENT & OUTCOME: Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole. DISCUSSION: This case highlights the importance of monitoring ATRA's side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.

Ibrutinib-induced polyneuropathy: A case report.

INTRODUCTION: Ibrutinib is an oral irreversible inhibitor of Bruton's tyrosine kinase signaling. It is a well-tolerated agent with some side-effects, the most common of which are atrial fibrillation, diarrhea, upper respiratory tract infection, fatigue, nausea, rash and cytopenias. Most of these toxicities are mild, although some have a severe clinical course. CASE REPORT: The case is here reported of a chronic lymphocytic leukemia patient with ibrutinib-induced polyneuropathy. A 63-year-old male patient with chronic lymphocytic leukemia was given ibrutinib as a third line treatment regimen. After the 10th month of therapy he had progressive complaints of numbness and tingling in his legs. The patient was diagnosed as grade 3 sensorineural polyneuropathy with electromyography.Management and outcome: Considering that ibrutinib treatment may cause neuropathy, the ibrutinib was discontinued, after which the neuropathic complaints improved. However, the neck and axillary lymph nodes were enlarged and treatment had to be re-started therefore ibrutinib was started at a low dose and gradually increased. The patient is currently in the 14th month of treatment and still using ibrutinib without any severe side-effects. DISCUSSION: To the best of our knowledge, polyneuropathy as a unique side-effect of ibrutinib has not been previously reported. In addition to the well-known side effects of ibrutinib treatment, it should be kept in mind that polyneuropathy may also develop.

Comparison of maintenance regimens in Acute Promyelocytic Leukemia patients.

Maintenance therapy in APL is still a standard especially in high-risk patients treated with chemotherapy+ATRA combination whereas the role of the maintenance therapy in low-risk patients is controversial. This study aims to compare the efficacy and toxicity of ATRA monotherapy and ATRA+MTX+ 6-MP combination as the maintenance treatment for 2 years in APL patients who achieved molecular complete response after induction and consolidation with ATRA+chemotherapy. A total of 71 patients from 4 different centers were included in this study. After a median follow-up of 54 months (5-180 months), the 5-year RFS was 89 % in the ATRA monotherapy arm, the 5-year RFS was 78.5 % in the combined treatment arm (p = 0.643, HR:1.3, 95 % CI: 0.35-5.3). Hematological toxicity in all grades and Grade III/IV hematological toxicity was observed significantly more in the combined treatment arm than in the ATRA monotherapy arm (All grades: 76.9 % vs 18.9 %, p < 0.001; Grade III/IV: 20.5 % vs. 3.1 %, p = 0.035). Hepatotoxicity at all levels was significantly higher in the combined treatment arm than in the ATRA monotherapy arm (61.5 % vs 25 %, p = 0.002). Our study concluded that two years of ATRA monotherapy and combined maintenance therapy, both of which were found to be similar in terms of disease control and long term survival, ATRA Monotherapy could be a safer maintenance treatment option since both hematological and non-hematological toxicities were observed less often in the ATRA monotherapy arm.

Mean platelet volume is a predictive and prognostic marker for patients with acute myeloid leukemia: a two-center retrospective analysis.

There are only a few predictive markers that can truly aid therapy decisions in patients with acute myeloid leukemia (AML). The current study aimed to examine the impact of easily available common laboratory parameters on the course and prognosis of patients with AML. Gender, initial bone marrow blast percentage, mean platelet volume (MPV), lymphocyte-to-monocyte ratio, treatment regimen, and complete remission (CR1) were found to have a statistically significant effect on both OS and PFS (p < 0.05). Only MPV, LDH, and initial treatment regimen were found to have a significant effect on CR1 achievement (p < 0.05). According to the current study, besides the induction regimen, only MPV was seen to affect short and long-term outcomes including both CR achievement, OS and PFS. MPV can be considered as a predictive or prognostic marker in patients with AML. Patients with higher MPV at the time of diagnosis should be evaluated carefully.

Pralatrexate experience in PTCL: A multicenter retrospective study from Turkey.

PURPOSE: Pralatrexate is a new generation antifolate treatment agent used for the treatment of relapsed or refractory peripheral T-cell lymphomas. This study aims to determine the general characteristics of the patients receiving pralatrexate therapy in Turkey, contributing to the literature on the effectiveness of pralatrexate therapy in peripheral T-cell lymphomas by determining the response levels of such patients to the therapy. The study also attempts to clinically examine the major side effects observed in patients during treatment with pralatrexate. METHODS: The study included patients with peripheral T-cell lymphoma followed up in the hematology units of several hospitals in Turkey. Overall, 20 patients aged 18 and over were included in the study. RESULTS: The median age at the time of diagnosis was 58.5 years. PTCL-NOS (Peripheral T-cell lymphoma, not otherwise specified) subtype was in 40% of patients, making the PTCL-NOS the most common subtype in the study. In general, most patients were diagnosed with disease at an advanced stage. Pralatrexate therapy was given to the patients at a median treatment line of 3.5. Pralatrexate dose reduction was required in only 3 patients (15%). Response to pralatrexate therapy with partial remission (PR) and above was observed in 11 (55%) of the patients. CONCLUSION: Pralatrexate seemed to be a promising novel treatment in relapsed refractory PTCL patients. However, patients receiving pralatrexate should be followed up carefully for skin reactions, mucosal side effects, thrombocytopenia and neutropenia.

A Signet Ring Cell Carcinoma Presented as Refractory Acquired Thrombotic Thrombocytopenic Purpura.

Microangiopathic hemolytic anemia (MAHA) can be observed as a paraneoplastic syndrome (PS) in certain tumors. MAHA-related signet ring cell carcinoma (SRCC) of an unknown origin is very infrequent. Herein we present a SRCC case presented with refractory acquired thrombotic thrombocytopenic purpura (TTP). A 35-year-old man applied to the emergency service with fatigue and headache. His laboratory tests resulted as white blood cell 9,020/µL, hemoglobin 3.5 g/dL, platelet 18,000/µL. Schistocytes, micro-spherocytes, and thrombocytopenia were observed in his blood smear. MAHA was present and he was considered as having TTP. Plasma exchange treatment was initiated; however, he was refractory to this treatment. Thorax and abdomen computerized tomography revealed thickening of minor curvature in stomach corpus with hepatogastric and paraceliac lymphadenopathy. Bone marrow (BM) investigation by our clinic resulted as the metastasis of adenocarcinoma. Ulceration and necrosis were observed by gastric endoscopy procedure. Biopsy was taken during endoscopic intervention, which resulted as SRCC. MAHA may be seen as a PS in some tumors, especially gastric cancers. Tumor-related MAHA is generally accompanied by BM metastases. As a result, BM investigation may be used as the main diagnostic method to find the underlying cancer. The clinical course of cases with tumor-related MAHA is usually poor, and these cases are usually refractory to plasma exchange treatment. In conclusion, physicians should suspect a malignancy and BM involvement when faced with a case of refractory TTP.