Anorectal Pathologies in the Course of Acute Leukaemias; Predictive Parameters.

Introduction: Patients with leukaemia are exposed to infections as long as they are neutropenic. During this period, anorectal pathologies are among the common foci of infection with high mortality. In this study, we aim to investigate the factors that may have a predictive effect on early diagnosis and rapid intervention in perianal complications occurring in neutropenic patients diagnosed with leukaemia. Materials and Methods: A total of 90 patients with acute leukaemia, including 45 patients with anorectal pathology and 45 patients without anorectal pathology, were analysed. Demographics, blood group, BMI, haemogram and biochemical parameters at the time of diagnosis, and types of perianal pathology were recorded. Results: In the group of patients with anorectal pathology, WBC, lymphocytes, monocytes, and LDH were significantly (p<0.05) higher, and platelets, MPV, and PCT were significantly (p<0.05) lower. The multivariate model showed significant-independent (p<0.05) efficacy of WBC and MPV values in differentiating patients with and without anorectal pathology. A significant efficacy was observed at the WBC cut-off of 17000 [area under the curve 0.656 (0.542-0.770)] and the MPV cut-off of 10 [area under the curve 0.667 (0.554-0.780)] in differentiating patients with and without anorectal pathology. Discussion: Anorectal pathologies are common foci of infection in patients with acute leukaemia. Having predictive parameters that may help for early intervention will help the clinician. This is the first study in the literature to compare a control group with a group with anorectal pathologies in leukaemia patients providing a cut-off for WBC.

Prognostic Impact of Bone Marrow Fibrosis and Effects of Tyrosine Kinase Inhibitors on Bone Marrow Fibrosis in Chronic Myeloid Leukemia.

BACKGROUND: Myelofibrosis is reported in around 40% of newly diagnosed chronic myeloid leukemia (CML) patients and have an important role in the pathobiology and prognosis of CML. This retrospective study aimed to evaluate the effects of bone marrow (BM) fibrosis on disease prognosis and the effects of specific tyrosine-kinase inhibitors (TKIs) on BM fibrosis in CML patients. METHODS: The study included 96 patients (>18 years) diagnosed with chronic phase (CP) CML. The clinical and demographic information were collected from the medical files. Post-treatment BM aspirate and core biopsy samples were analyzed for the presence of fibrosis and dysplasia. RESULTS: The mean age of the study patients was 52.69 years; 47.9% of the patients were female. At the onset, 53 (63.1%) patients had BM fibrosis. The difference in the overall survival of the patients with respect to BM fibrosis grades was significant (p = .001). Within the BM fibrosis grade groups, there were significant differences between grade 0 vs. grade 2, grade 0 vs. grade 3, and grade 1 vs. grade 3 (p = .005, p = .002, and p = .003 respectively) There was no significant association between the presence of BM fibrosis at the onset and not responding to first-line therapy (p = .724). Moreover, no significant association was found between the presence of BM fibrosis at the onset and molecular (p = .623) or cytogenetic response (p = .535) to first-line therapy. Additionally, the association between the type of second-line and third-line therapy and molecular response (p = .773 and p = .424, respectively) or cytogenetic response (p = .298 and p = .641) was not significant. CONCLUSION: Although BM fibrosis seems to be a crucial complication of CML with a poor prognosis, it can be reversed via TKI treatment which may result in improved survival. It might be considered to check the BM for this complication on a regular basis during therapies to test its prognostic influence in CML patients in prospective controlled trials. Further studies focused on this issue are required to utilize BM fibrosis as a candidate prognostic factor.

Change in Hepatitis B Surface Antibody Titers After Chemotherapy in Patients With Hematological Malignancies.

Background The change in hepatitis B surface antibody (anti-HBs) titers after chemotherapy (CT) in patients with hematological malignancy, affecting factors, and its clinical implications have not been sufficiently understood. Therefore, we aim to evaluate the change in anti-HBs titers and hepatitis B virus reactivation (HBVr) after CT. Methods This retrospective study enrolled patients with hematological malignancies who received CT between 2013 and 2021. All patients were followed up for HBVr and a change in anti-HBs titers for one year. Results Overall, 192 patients were included. In total, 33.9% of the patients were anti-HBs (+) and 26% of the patients were anti-HBc (+) ± anti-HBs (+). Hepatitis B virus (HBV) prophylaxis was given to 35 (70%) of 50 Anti-HBc (+) patients. Tenofovir disoproxil fumarate and entecavir prophylaxis were initiated in 25 (71.4%) and 10 (28.6%) patients, respectively. A significant decrease was found in anti-HBs titers of all patients (p=0.017). A significant decrease was also found in anti-HBs titers of HBc IgG (+) patients and those who received four or more courses of CT (p=0.025; p=0.041). HBVr was not diagnosed in any of the patients. Conclusion Chemotherapeutic agents administered for hematological malignancy have serious immunosuppression effects. In these patients, anti-HBs titers may decrease or become negative one year after CT. Anti-HBs titer before CT or its change after CT may not constitute a risk for HBVr patients who received HBV prophylaxis in line with current guidelines and these recommendations.

Long-term Results of Imatinib Discontinuation in Patients with Chronic-phase Chronic Myeloid Leukemia: A National Multicenter Prospective Study

Objective: The discovery of imatinib was a milestone for chronic myeloid leukemia (CML). As the life expectancy of CML patients has approached that of the general population, research has shifted towards improving quality of life and economic considerations. After 2010, it was shown that some patients could maintain molecular response even after discontinuing imatinib. This national multicenter prospective cohort study aimed to observe the long-term consequences of discontinuing imatinib therapy in adult chronic-phase CML patients. Materials and Methods: We enrolled 41 CML patients from 4 different centers in this non-randomized single-arm trial. Molecular responses of all patients were re-evaluated using real-time polymerase chain reaction at a single center. The median follow-up time after imatinib discontinuation was 48 months (minimum-maximum: 6-81 months). Results: The rate of molecular relapse-free survival at 48 months was 33.2% (confidence interval: 48.2-18.2). Twenty-seven of 41 patients lost their major molecular response, treatment was started again, and deep molecular response was re-achieved with imatinib in all cases. There was no significant relationship between molecular relapse and clinical factors such as duration of treatment or molecular response status. Discontinuing imatinib resulted in savings of approximately 4,392,000 Turkish lira or 245,150 US dollars. Conclusion: Tyrosine kinase inhibitor discontinuation with close molecular monitoring is a safe option and provides important national economic benefits for chronic phase CML patients. This approach should be considered for all eligible patients. This is the first tyrosine kinase inhibitor discontinuation study from Türkiye.

Evaluation of Second Primary Cancer Risk Among Chronic Lymphocytic Leukemia Patients: Multicenter Study.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing second primary cancers (SPC). The aim of this study is to determine the frequency of SPC in CLL patients and determine the relationship between these cancers and their treatment status, cytogenetic factors, and other risk factors. METHODS: The study was designed as multicenter and retroprospective. The sample comprised 553 subjects with a CLL diagnosis. Data collection commenced in August 2016, and completed at May 2021. RESULTS: Fifty one of 553 patients followed for CLL, had a history of SPC. SPC development rate was 9.2%. Epithelial tumors were mostly observed. According to the incidence skin, lymphoma, renal, breast, lung, gastrointestinal system, thyroid, malignant melanoma, prostate, Kaposi's sarcoma, neuroendocrine tumor, ovarian, larynx and salivary gland cancers were detected respectively. The 13q deletion was the most common genetic abnormality in those who developed SPC, and the frequency of 13q deletion was found to be increased statistically significant in those with malignancy, compared to those who did not. CONCLUSION: In CLL patients with SPC, the age of diagnosis, 13q and CD38 positivity, and treatment rates with fludarabine and monoclonal antibodies were found to be higher. Also, we determined that SPC frequency increased independently from hemogram values (except hemoglobin values), ß2 microglobulin level on admission, number of treatment lines, and genetic mutations other than 13q, in CLL patients. In addition, the mortality rate was higher in CLL patients with SPC and they were prone to be in advanced stages at the time of diagnosis.

Real-world data on the effectiveness and safety of Ixazomib-Lenalidomide-Dexamethasone therapy in relapsed/refractory multiple myeloma patients: a multicenter experience in Turkey.

A multicenter, retrospective, observational study was conducted to explore effectiveness and safety of ixazomib plus lenalidomide with dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM) patients following at least ≥ two lines of therapy. Patients' treatment responses, overall response rate, progression-free survival rate, and adverse events were recorded. Mean age of 54 patients was 66.5 ± 9.1 years. There were 20 patients (37.0%) with progression. Median progression-free survival was 13 months in patients who received a median of three therapy lines in a 7.5-month follow-up period. Overall response rate was 38.5%. Of 54 patients, 19 (40.4%) had at least one adverse event, and nine (19.1%) had an adverse event of at least grade 3 or more. Of 72 adverse events observed in 47 patients, 68% were grade 1 or 2. Treatment was not stopped in any patient due to adverse events. IRd combination therapy was effective and safe in heavily treated RRMM patients.

Treatment options in primary mediastinal B cell lymphoma patients, retrospective multicentric analysis; a Turkish oncology group study.

Introduction and Aim: Primary mediastinal B-cell lymphomas (PMBL) are aggressive B- cell lymphomas. Although the initial treatment models vary in PMBL, appropriate treatment methods are not known. We aim to show real-life data on health outcomes in adult patients with PMBL who received various type of chemoimmunotherapies in Turkey. Method: We analyzed the data of 61 patients who received treatments for PMBL from 2010 to 2020. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) of the patients were evaluated. Results: 61 patients were observed in this study. The mean age of the study group was 38.4 ± 13.5 years. From among them, 49.2% of the patients were female (n = 30). For first-line therapy, 33 of them had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen (54%). Twenty-five patients had received rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH-R) regimen. The ORR was 77%. The median OS and PFS were as follows: 25 months (95% CI: 20.4-29.4) and 13 months (95% CI: 8.6-17.3), respectively. The OS and PFS at 12 months were 91.3% and 50%, respectively. The OS and PFS at five years were 64.9% and 36.7%, respectively. Median follow-up time period was 20 months (IQR 8.5-38.5). Conclusion: R-CHOP and DA-EPOCH-R showed good results in PMBL. These remain one of the best determined systemic treatment options for first-line therapy. Also, the treatment was associated with good efficacy and tolerability.

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.

A rare case of pulmonary lymphomatoid granulomatosis complicated with venous thrombosis.

Lymphomatoid granulomatosis (LG) is Epstein-Barr virus associated and aggressive B cell lymphoproliferative disease. The most common sites of involvement are lungs, skin, kidneys, liver and central nervous system. The clinical presentation of pulmonary LG may mimic infectious diseases, malignancies or vasculitis. While treatment approach of low grade disease is watch and wait, patients with advanced stage require aggressive treatment with chemotherapy. Patients with hematological malignancy as well as solid tumors are at increased risk of venous thromboembolic events (VTE). We reported here in a case of pulmonary LG who was complicated with VTE during treatment with chemo-immunotherapy After 4 cycles of R-CHOP, she achieved complete remission for LG and was followed up without relapse for 2 years. She was anticoagulated with Low-Molecular-Weight Heparin (LMWH) during chemotherapy period, and the thrombus improved over the next several weeks. While on this paper written, patient completed her pregnancy successfully under anticoagulation prophylaxis.

Association of Thrombin-Activatable Fibrinolysis Inhibitor with Acute Pulmonary Embolism.

BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis and high levels may have an association with thrombosis. The aim of the current study was to investigate the association of TAFI antigen levels with pulmonary thromboembolism (PTE). PATIENTS AND METHODS: A case-control study was conducted with 29 patients with PTE and 17 age- and gender-matched control individuals. Plasma levels of TAFI were measured at the time of diagnosis, then at 3 and 6 months after the event. RESULTS: Initial TAFI levels (%) were higher in patients with PTE than in the control group (190,0 [65,0-250,0] vs 133,0 [83,0-153,0]; p = 0.003). TAFI levels significantly decreased at the third and sixth months after initial diagnosis (p < 0.05). The percentage reductions in TAFI levels were 12 and 36.8% at 3 and 6 months, respectively. The Odss ratio (OR) of TAFI level for PTE was found to be 1.024 (95% CI: 1.007-1.040; p = 0.005). There was no significant correlation of initial TAFI levels with age, gender, smoking status, history of thrombosis, pulmonary artery pressure, and D-dimer levels (p > 0.05). In the sixth month of treatment, patients with residual thrombosis were seen to have similar baseline levels and reductions of TAFI as patients without residual thrombosis (p > 0.05). CONCLUSION: The result of this study suggests that high TAFI levels may have a role in the occurrence of PTE without impact on treatment outcome.

The outcome of COVID-19 in patients with hematological malignancy.

Objective: The aim of this study was to examine the effect of coronavirus disease 2019 (COVID-19) on the malignancy-related clinical course and overall survival, and to determine the factors affecting mortality. Methods: This retrospective study included 77 patients with hematological cancer and COVID-19. Patients were sub-grouped for analysis as survivors and non-survivors. Results: COVID-19 was seen more frequently in myeloproliferative neoplasms (MPN), non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. Mortality rate due to COVID-19 was 20.8%. No statistically significant difference was determined between the survivor and non-survivor groups with respect to age and gender, presence of any comorbidity, leukocyte, neutrophil, lymphocyte, and monocyte values. Platelet count and hemoglobin count were significantly lower in the group with mortality than in the group with recovery. Conclusion: It should be kept in mind that low hemoglobin and platelet levels contribute to mortality. In addition, it is important to protect patients with hematological cancer from COVID-19 and undertake effective vaccination due to its mortal course.

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.

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.

Efficacy and safety of plasmapheresis in symptomatic hyperviscosity and cast nephropathy: A Multicenter Experience in Turkey.

BACKGROUND AND OBJECTIVES: Cast nephropathy (CN) and hyperviscosity (HV), which we encounter in plasma cell diseases, are serious clinical manifestations that increase mortality and morbidity if not managed well in the early period. Therapeutic plasma exchange (TPE) procedures based on the removal of patient plasma is a frequently preferred treatment modality. TPE is recommended at varying levels of evidence for the treatment of CN and HV in plasma cell disorders. MATERIAL AND METHODS: A total of 61 patients, 50 with multipl myeloma (MM) and 10 with Waldenström macroglobulinemia (WM), who underwent TPE for CN and HV, were included in our multicenter, and retrospective study. RESULTS: A statistically significant decrease was found in all disease-related biochemical markers, which were measured 1 week after the application of TPE added to standard medical treatment (IgG; p < 0.001, IgM; p = 0.004, IgA; p = 0.14, kappa light chain; p < 0.001, lambda light chain; p < 0.001, ß-2 microglobulin; p < 0.001, total protein; p < 0.001, albumin; p < 0.001, LDH; p = 0.02, creatine; p < 0.001, hemoglobin; p = 0.010). Clinically, all 11 patients who underwent TPE for HV responded. While a partial response (PR: 80 %) was obtained in 40 of 50 MM patients with CN, no response was obtained in 10 patients (non-response: 20 %). CONCLUSION: In conclusion, it was observed that TPE reduced all biochemical markers related to HV and CN, while making a significant contribution to clinical improvement. We believe that adding TPE to the standard treatment in this patient group will reduce mortality and morbidity in the early period and have a positive effect on survival in the long term.

Brentuximab vedotin consolidation therapy after autologous stem-cell transplantation in patients with high-risk Hodgkin lymphoma: Multicenter retrospective study.

The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Thus, we aimed to determine the impact and safety of BV as maintenance after ASCT in real-world patients. Seventy-five patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease <12 months (n = 61), lack of complete response (CR) to the last salvage regimen (n = 51), and having had at least two salvage regimens (n = 29). At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in 6, and SD in 3 patients), 25 had progressed. Ten died in the follow-up, eight with progressive disease and two due to infection while in CR. The 2-year PFS and OS rates were 67.75% (95% confidence interval [CI]: 0.55-0.77) and 87.61% (95% CI: 0.76-0.94), respectively. Seventeen patients (23%) received BV in the pre-ASCT treatment lines, and there was no survival difference between the BV-naïve and BV-exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to adverse event in 12 patients. Consolidation with BV after ASCT can achieve a 2-year PFS of 67.75% (95% CI: 0.55-0.75) with an acceptable toxicity profile.

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.

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.