Combination Therapy Of Cyclophosphamide Research Articles

A Combination Therapy of Cyclophosphamide and Immunomodulating Agents in Cancer.

Cyclophosphamide is a precursor of alkylating nitrogen mustard and was initially claimed to have antineoplastic and immunosuppressive properties. However, the role of cyclo-phosphamide as an immune activator has also been reported, depending on the dosage used. The application of lower-dose cyclophosphamide has emerged as a potential approach to cancer treatment. Cyclophosphamide selectively depletes regulatory T cells (Tregs), which dampens the immunological response, thereby rebalancing the immune system to allow other immune cells to act more efficiently. Cyclophosphamide can be either a friend or a foe in cancer treatment, de-pending on the therapeutic regime. The following questions remain to be answered: Can the cy-clophosphamide be used in the presence of other agents? Is there any single immunotherapeutic agent that acts synergistically with cyclophosphamide to effectively alter the immunosuppres-sive tumor microenvironment? This review emphasizes the role of cyclophosphamide as an im-mune modulator, both alone and in combination with other immunotherapeutic agents, for effec-tive cancer treatment in preclinical and clinical settings.

#3076 A UK parallel cohort study on renal ANCA associated vasculitis outcomes for avacopan exposed and matched unexposed cohorts

Abstract Background and Aims Avacopan was approved in the UK for severe ANCA associated vasculitis (AAV) in December 2022. The ADVOCATE trial found the differential effect of avacopan on kidney function was greatest in patients with the lowest estimated glomerular filtration rate (eGFR), at highest risk of progression to end stage kidney disease (ESKD). Patients with an eGFR <15 ml/min/1.73 m2, pulmonary haemorrhage requiring invasive ventilation, under 12 months prognosis, use of plasma exchange and dual therapy with cyclophosphamide (CYC) and rituximab (RTX) were excluded from ADVOCATE; all common scenarios in real life practice. We aim to provide further information on these subgroups and evaluate 6 month renal outcome data in the UK. Method Parallel cohort study on renal AAV outcomes for avacopan exposed and matched unexposed cohorts, with severe, active GPA or MPA. 120 patients on avacopan from 7 UK centres have been recruited to date. Controls matched by renal function and age will be presented. Comparisons of ESKD, delta eGFR, eGFR recovery, reduction in proteinuria/haematuria, remission, relapse and mortality will be presented, with subgroup analyses for eGFR<15 ml/min/1.73 m2. Steroid exposure will be presented. Results Baseline characteristics of the avacopan cohort are below. Most received oral prednisolone at avacopan initiation (89%, n = 107) and 54% received intravenous methylprednisolone (n = 65). The majority received RTX alone (44%, n = 53) or RTX and CYC combination therapy (43%, n = 52). Fewer received CYC alone (9%, n = 11) and 3% were initiated on alternative immunosuppression (n = 4). 26% (n = 31) underwent plasma exchange and 13% required haemodialysis (n=16). 3% of patients have died. Excluding dialysis dependent patients at presentation, median eGFR was 22ml/min/1.73 m2 (IQR 10-36). eGFR at the time of avacopan initiation was 21ml/min/1.73 m2 (IQR 11-34). Conclusion Avacopan is commonly being used to treat nephritis in patients with a low eGFR, including haemodialysis dependent and elderly patients. Avacopan is frequently used with RTX and CYC combination therapy. 6 month outcome data will provide new data on important patient subgroups excluded from the ADVOCATE trial.

Real-World Experience With Avacopan in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Postmarketing data on outcomes of avacopan use in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are lacking. We performed a multicenter retrospective analysis of 92 patients with newly diagnosed or relapsing AAV who received therapy with avacopan. The coprimary outcome measures were clinical remission at 26 and 52 weeks. We use descriptive statistics and univariate logistic regression to assess outcomes and predictors of remission, respectively. Of the 92 patients, 23% (n = 21) had a baseline estimated glomerular filtration rate (eGFR)< 15 ml/min per 1.73 m2 and 10% on kidney replacement therapy at baseline. Among those with kidney involvement, mean (SD) enrollment eGFR was 33 (27) ml/min per 1.73 m2 with a mean (SD) change of+12 (25) and+20 (23) ml/min per 1.73 m2 at weeks 26 and 52, respectively. In addition to avacopan, 47% of patients received combination therapy of rituximab and low-dose cyclophosphamide, and 14% of patients received plasma exchange (PLEX). After induction, the median (interquartile range [IQR]) time to start avacopan was 3.6 (2.1-7.7) weeks, and the median time to discontinue prednisone after starting avacopan was 5.6 (3.3-9.5) weeks. Clinical remission was achieved in 90% of patients at week 26 and 84% of patients at week 52. Of the patients, 20% stopped avacopan due to adverse events, with the most common being elevated serum aminotransferases (4.3%). A high rate of remission and an acceptable safety profile were observed with the use of avacopan in the treatment of AAV in this postmarketing analysis, including the populations excluded from the ADVOCATE trial.

Successful treatment of refractory interstitial lung disease with cyclophosphamide and pirfenidone in a new onset of juvenile SLE; a case report

Introduction and importance: Systemic lupus erythematosus is a systemic immune disease, presented with a broad spectrum of clinical manifestations. The occurrence of interstitial lung disease as the initial manifestation of systemic lupus erythematosus is very rare. Case presentation: We present the case of a 6-year-old girl who presented with symptoms of fatigue, fever, oral ulcers, and dry cough with difficulty breathing. On physical examination, the patient had fever and oral ulcers, in addition of acute phase reactant analysis, positive ANA and double stranded DNA. Chest CT images showed nonspecific interstitial pneumonia + organizing pneumonia pattern, leading to the diagnosis of onset of systemic lupus erythematosus with interstitial lung disease. The patient was treated with steroids and azathioprine for one year, and the radiological and immunological resolution was noted. However, the patient continued to cough, have difficulty breathing, and was readmitted to the hospital due to SLE recurrence after 1 year of follow-up. Despite continued corticosteroid therapy and monthly administration of steroids and cyclophosphamide (CYS) for 6 months, the patient’s respiratory symptoms and chest X-ray results did not improve significantly. The patient was then prescribed a daily regimen of cyclophosphamide and pirfenidone, which was found to be effective in reducing the steroid dose and achieving remission after one year of follow-up. Clinical discussion: Treatment of connective tissue disease-associated interstitial lung disease is difficult due to a lack of treatment data. Conclusion: This case provided evidence of the efficacy of combination therapy of pirfenidone and cyclophosphamide for refractory connective tissue disease-associated interstitial lung disease in young children.

Symposium 6

The ultimate goal of treatment of systemic lupus erythematosus (SLE) is to prolong survival without compromising the quality of life. The survival rates of SLE have plateaued since the 2000s’ and morbidities related to disease activity and treatment are still problematic. A big unmet need for SLE therapy is to develop strategies that can enhance efficacy, reduce disease flares and drug related complications. Cocktail immunosuppressive therapies for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, risk of infective complications, adoption of a step-up or step-down approach and the choice of agents are still controversial, partly because of the issue of cost-effectiveness. Belimumab is the first biological agent licensed for pediatric and adult patients with renal and non-renal SLE, based on several pivotal randomized controlled trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, BLISS-LN). The continuous use of belimumab enables reduction of disease flares, glucocorticoid doses and organ damage. Anifrolumab, a monoclonal antibody against type I interferon receptors, has shown efficacy for non-renal SLE in the TULIP studies. It is recently licensed for moderate to severe SLE patients who are receiving standard therapies. Although rituximab did not show benefit in renal and non-renal SLE, it is commonly used off-label to treat refractory lupus manifestations. The newer generation anti-CD20 biologic, obinutuzumab, shows promising preliminary results in a phase 2 lupus nephritis (LN) trial. Combination of anti-CD20 and anti-BAFF is being studied in LN but the results are conflicting hitherto. Ianalumab, a monoclonal antibody against BAFF receptor that exhibits dual mechanisms of action (BAFF inhibition and B cell depletion), is being studied in LN. The updated 2023 EULAR recommendations for SLE have included the role of biological agents in the treatment algorithm. Belimumab and anifrolumab may be considered in non-major organ SLE, including skin disease, that is refractory to hydroxychloroquine with or without other immunosuppressive agents. Initial combination therapy of glucocorticoids, mycophenolate mofetil or low dose cyclophosphamide, with belimumab is an option for the treatment of severe LN, and belimumab may be used as long-term maintenance therapy of SLE/LN. In this talk, the evidence and the role of the older and newer biologic and targeted agents in SLE/LN will be reviewed.

#4710 CYCLOPHOSPHAMIDE INDUCTION TREATMENT IN ANCA-ASSOCIATED VASCULITIS WITH RENAL AND PULMONARY INVOLVEMENT: OUTCOMES AND SIDE EFFECTS

Abstract Background and Aims ANCA associated vasculitis are necrotaizing vasculitis of small and medium vassels - which cause organ damage. They are relatively rare diseases with an estimated prevalence of 200–400 cases per million people [1]. Pauci-immune necrotizing and crescentic glomerulonephritis (GN) is a frequent component of ANCA-associated vasculitis that can cause rapidly progressive Acute Kidney Injury (AKI). Less frequently, it can cause low progressive Chronic Kidney Disease (CKD) [2]. Combination therapy of steroids and cyclophosphamide has improved 5-years survival up to 70-90% but it can cause serious side effects including infectious episodes [3], bone marrow suppression and myelodysplasia. We present a case highlighting treatment modalities and our decision making. Method Our retrospective study analyzes the case of a 63-year-old male presenting with progressive dyspnea and hemoptysis. A chest CT suggested diffuse alveolar hemorrhage. The blood tests showed onset of AKI with 7.68 mg/dl serum creatinine (normal values 0.72-1.25), mild proteinuria and hematuria. A kidney and pulmonary vasculitis was suspected and the c-ANCA serum value was elevated at &amp;gt;500 IU/ml. Three cycles of Plasma Exchange (PEX) were performed and methylprednisolone was given (500 mg for 3 days, 1 g on the 4th day) followed by cyclophosphamide boluses of 1 g/week for 4 weeks. Broad-spectrum antibiotics and antifungal therapy was administered to prevent secondary infections. Due to the further worsening of the renal function, three hemodialysis treatments and a cascade filtration were performed continuing with cyclophoshamide 1 g/day orally and methylprednisolone 60 mg/day. Cyclophosphamide therapy was discontinued due to thrombocytopenia and progressive leukopenia. Filgastrim 30MU/0.5 ml was administered for five days until the resolution of the pancytopenia when cyclophosphamide 50 mg 2cp+1cp was resumed. Results A one-month follow-up CT showed reduction in hemorrhagic opacities and the c-ANCA level was significantly reduced. Steroid dosing was progressively reduced and the patient was discharged with methylprednisolone 16mg 2cp+1/2cp tapering over 6 months and cyclophosphamide 50 mg 2cp+1cp. Serum creatinine levels improved from 2.64 mg% at discharge to 1.6 mg% at follow up. Conclusion When treating c-ANCA vasculitis with corticosteroids and cyclophosphamide, routine evaluation of complete blood count parameters is necessary to prevent bone marrow toxicity. We continued methylprednisolone and cyclophosphamide for six months, obtaining a total clinical remission despite side effects induced by the state of immunosuppression (oral cavity mycosis, bone marrow toxicity and CMV reactivation).

Effects of Sleep Disturbance before Initiation of Epirubicin and Cyclophosphamide Combination Therapy on Chemotherapy-induced Nausea and Vomiting for Breast Cancer Patients

Effects of Sleep Disturbance before Initiation of Epirubicin and Cyclophosphamide Combination Therapy on Chemotherapy-induced Nausea and Vomiting for Breast Cancer Patients

Combination therapy of oral cyclophosphamide and bevacizumab for patients with recurrent ovarian and peritoneal cancer.

Chemotherapy for patients with recurrent cancer aims to obtain survival benefits, relieve symptoms, and improve quality of life. We used oral cyclophosphamide and bevacizumab (BEV) combination therapy in recurrent ovarian and peritoneal cancer cases, where standard chemotherapy was infeasible. Subsequently, we evaluated the safety and efficacy of this treatment. Between August 2014 and June 2020, patients received the following regimen: oral cyclophosphamide 50 mg daily and intravenous cyclic BEV 15 mg/kg every 3 weeks. Data from 2 facilities were retrospectively analyzed. Twenty-two patients were enrolled (20 with ovarian cancer and two with peritoneal cancer). The median follow-up period and age were 18.9 months (range, 5.0-51.5) and 60 years (range 37-81), respectively. Sixteen patients had platinum resistance. The median number of previous chemotherapy regimens was 2.5 (range 0-5). The median implementation cycle was five (range 2-14). Eighteen patients discontinued treatment due to side effects (3 patient) and disease progression (15 patient). Grade 2 toxicities included neutropenia (1 patient), proteinuria (1 patient), hypertension (2 patient), and esophagitis (1 patient). Two patients had complete response and one had a partial response. Five patients had stable disease. The response rate in platinum-sensitive recurrence was 33.3%, and 7.1% in platinum-resistant recurrence, and a clinical benefit was found in 8 (36.3%) patients. The median PFS and overall survival from cyclophosphamide and BEV initiation was 5.3 months (range, 0.8-23.5) and 9.2 months (range, 4.8-51.5), respectively. The combination of oral cyclophosphamide and BEV does not have a high response rate, but is well-tolerated and can be used safely in patients who are difficult to treat after second-line chemotherapy. Data from 2 facilities were retrospectively analyzed.

Effect of Secondary Prophylactic G-CSF on the Occurrence of Febrile Neutropenia in Breast Cancer.

Docetaxel and cyclophosphamide (TC) combination therapy is widely used as adjuvant chemotherapy for early-stage breast cancer and is associated with a high incidence of febrile neutropenia (FN). Granulocyte colony-stimulating factor (G-CSF) is recommended in the primary prevention of febrile neutropenia (FN). This study aimed to evaluate the FN-suppressing effect of G-CSF in patients with breast cancer receiving TC. We performed 272 treatment cycles after FN onset in 106 patients with breast cancer receiving TC. We retrospectively evaluated the effect of G-CSF as secondary prophylaxis. The frequency of FN was calculated based on the treatment cycles to adjust for differences in the number of cycles per case and FN occurrence. FN occurred in 58 cycles (21.3%). The incidence of FN with and without secondary prophylactic G-CSF was 10.1% and 25.9%, respectively (p=0.003). Multivariate analysis showed secondary prophylactic G-CSF administration to be an independent predictor of FN incidence [odds ratio (OR)=0.33, 95% confidence interval (CI)=0.14-0.74, p=0.007]. Secondary prophylaxis with G-CSF is recommended for patients with breast cancer undergoing TC chemotherapy to reduce the incidence of FN.

Impact of oral hygiene on febrile neutropenia during breast cancer chemotherapy.

Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer. A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed. The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 106 colony-forming units (CFU)/mL, cycle 2: 5.89 × 106CFU/mL, cycle 3: 4.61 × 106CFU/mL, cycle 4: 5.85 × 106CFU/mL, P = 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN. FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.

Real-world effectiveness of prophylactic granulocyte colony-stimulating factor (G-CSF) early (week 1) and late (weeks 2-3) in the cycle for the prevention of febrile neutropenia (FN) among patients (pts) with breast cancer (BC) after high FN–risk chemotherapy (chemo).

599 Background: G-CSF mitigates chemotherapy-induced neutropenia (CIN) and reduces FN risk. G-CSF moves the nadir of absolute neutrophil count (ANC) earlier (to week 1) in the chemo cycle and shortens nadir duration (Crawford, NEJM 1991), suggesting the potential for suboptimal CIN protection early (week 1) in the chemo cycle. The relative FN risk in week 1 vs. weeks 2-3 of the cycle with G-CSF is unknown and was analyzed compared with no G-CSF in the real-world setting with high FN risk chemo. Methods: Using a database of administrative claims representing 100% of fee-for-service Medicare, we analyzed BC pts who initiated docetaxel (T), doxorubicin (A), or cyclophosphamide (C) monotherapy or combination therapy between 01/01/2015 – 12/31/2019. Sample pts included adults aged ≥ 65 years with continuous coverage in Medicare Parts A, B, and D for 6 months before and 20 days after chemo initiation. Pts were categorized as receiving vs. not receiving G-CSF therapy within 3 days after chemo. Rate of FN events starting in week 1 vs. weeks 2-3 in cycle 1 was calculated. We defined FN as an inpatient admission with a primary or secondary diagnosis of neutropenia and measured the interval between chemo initiation and FN admission. Results: Among 18,788 Medicare beneficiaries with BC treated with T, A, and/or C, 72% received G-CSF therapy. More pts receiving G-CSF were treated with ≥ 2 of T, A, and/or C compared to pts who did not receive G-CSF (71% vs. 51%). Overall FN incidence in cycle 1 was significantly lower among pts receiving G-CSF (4.0%; n=546) compared to pts not receiving G-CSF (8.8%; n=462) (p&lt;0.0001). In pts with G-CSF, 81% (440/546) of all 1st-cycle FN events started in week 1 vs. 19% (106/546) in weeks 2-3. In pts not receiving G-CSF, the start of 1st-cycle FN events was more equally distributed: 41% (190/462) started in week 1 vs. 59% (272/462) in weeks 2-3. Results were robust to sensitivity analyses restricted to pts receiving ≥ 2 of T, A, and/or C. The rates of 1st-cycle FN events starting in weeks 1 and 2-3 with and without G-CSF following chemo initiation is shown below. Conclusions: Prophylactic G-CSF was highly effective for the prevention of FN in weeks 2-3, but relatively ineffective in week 1 of cycle 1 in the real-world setting, leaving pts largely unprotected during the first week. This represents an unmet medical need in week 1 of the cycle, despite use of G-CSF. Clinical trial information: NCT03294577. [Table: see text]

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma.

High-dose chemotherapy is frequently administered to patients with hematologic malignancies, thereby causing severe adverse drug reactions (ADRs) at a relatively high frequency. To precisely monitor ADRs, we developed a medication instruction sheet (MIS) for patients who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) combination therapy for non-Hodgkin's lymphoma (NHL). Herein, we evaluated the usefulness of the MIS for managing ADRs in patients who received R-CHOP therapy. We included patients aged ≥20 years who received R-CHOP therapy as first-line treatment for NHL at the Department of Hematology, Kyushu University Hospital, between August 2014 and December 2018. Medical professionals evaluated the possible occurrence of ADRs according to the present MIS and ADRs were graded according to the Common Toxicity Criteria, version 4.0 (National Cancer Institute, Bethesda, MD, USA). Finally, the accuracy of the MIS in predicting the occurrence of ADRs of different grades and during definite periods was evaluated. Seventy-five patients with NHL were included in the present study. Overall, 359 ADR events were monitored, which were predicted ADR items listed in the MIS. Among these, 254 (71%) events occurred during the same period as those listed in the MIS. The onset timing of any grade of an infusion reaction and peripheral neuropathy precisely matched those listed in the MIS. However, the accuracy of the MIS was reduced in patients with thrombocytopenia (42%). The present MIS could be useful for monitoring ADRs in patients with cancer undergoing R-CHOP therapy.

Efficacy and safety of plasma exchange in interstitial lung diseases with anti-melanoma differentiation-associated 5 gene antibody positive clinically amyopathic dermatomyositis

Objective Clinically amyopathic dermatomyositis (CADM) patients frequently develop refractory interstitial lung disease (ILD), with a poor prognosis. We aimed to verify the efficacy and safety of plasma exchange (PE) treatment for ILD in CADM. Method A retrospective case–control study was conducted to compare clinical outcomes with and without PE treatment in CADM-ILD patients refractory to combination therapy of high-dose glucocorticoids, calcineurin inhibitors, and cyclophosphamide. Among 19 enrolled patients, 11 were further treated with PE. We compared survival rates and other clinical characteristics. PE consisted of either fresh-frozen plasma or albumin as a replacement solution. Results Basal clinical characteristics at diagnosis, including age, gender, serum ferritin, Krebs von den Lungen-6 (KL-6), C-reactive protein, and respiratory function tests, did not differ between the two groups. The survival rate for treatment with PE was higher than for treatment without PE (91% and 50%, respectively, p < 0.05). Among PE-treated patients, anti-melanoma differentiation-associated gene-5 (anti-MDA-5) antibody titre, ferritin, and KL-6 as serological activity markers were sustainably reduced only after initiating PE. Therapeutic intervention with PE reduced the frequency of exacerbation of ILD requiring methylprednisolone pulse therapy. The occurrence of bacterial, fungal, and cytomegalovirus infection did not differ between the groups with and without PE, and adverse events associated with PE resolved with appropriate intervention. Conclusion Combination therapy with PE was associated with an improved survival rate, and may be effective for the management of refractory ILD in CADM patients. A personalized therapeutic strategy including PE could be introduced for fatal rapidly progressive ILD.

Cognitive impairment resulting from treatment with docetaxel, doxorubicin, and cyclophosphamide

Breast cancer is the most commonly diagnosed cancer among women and it is estimated that about 30% of newly diagnosed cancers in women will be breast cancers. While advancements in treating breast cancer have led to an average 5-year survival rate of 90%, many survivors experience cognitive impairments as a result of chemotherapy treatment. Doxorubicin, cyclophosphamide, and docetaxel (TAC) are commonly administered as breast cancer treatments; however, there are few studies that have tested the cognitive effects of TAC. In the current study, 12-week-old female C57BL/6 mice received 4 weekly intraperitoneal injections of either saline or a combination therapy of doxorubicin and cyclophosphamide followed by 4 weekly docetaxel injections. Four weeks after the last injection, mice were tested for hippocampus-dependent cognitive performance in the Y-maze and the Morris water maze. During Y-maze testing, mice exposed to TAC exhibited impairment. During the water maze assessment, all animals were able to locate the visible and hidden platform locations. However, mice that received the TAC presented with a significant impairment in spatial memory retention on the probe trial days. TAC treatment significantly decreases the dendritic complexity of arborization in the dentate gyrus region of the hippocampus. In addition, comparative proteomic analysis revealed downregulation of proteins within key metabolic and signaling pathways associated with cognitive dysfunction, such as oxidative phosphorylation, ephrin signaling, and calcium signaling.

Medical database analysis of japanese multiple myeloma patients with planned stem cell transplantation (MEDALIST) - a focus on healthcare resource utilization and cost.

This study explored the burden associated with stem cell mobilization, with or without cyclophosphamide (CPA), in patients who intended to receive autologous stem cell transplantation (ASCT) for multiple myeloma (MM). A Japanese health care claims database (MDV) was used to analyze the health care resource utilization patterns and medical cost between 2013 and 2016 (pre-plerixafor launch). The patients were further categorized into groups who received granulocyte-colony stimulating factor (G-CSF) alone or G-CSF + CPA group and analyzed in both mobilization and ASCT phases of treatment. Overall, there were more MM patients who were treated with G-CSF + CPA combination therapy than G-CSF alone. Length-of-stay was 1.6 times longer in the combination group during the mobilization phase. A reverse trend was observed during the ASCT phase. Direct cost was approximately 1.2 million yen during the mobilization phase and 2.3 million yen during the ASCT phase, with hospitalization basic fee accounting for the highest proportion in both groups and phases. A substantial amount of healthcare resource and cost was consumed in both phases. This study may serve as a basic reference for further health technology assessment of new medicines such as plerixafor. Further investigation of differences between treatment groups is warranted.

Severe but reversible pulmonary hypertension in scleromyxedema and multiple myeloma: a case report

BackgroundScleromyxedema is a progressive, systemic connective tissue disorder characterized by fibro-mucous skin lesions and increased serum monoclonal immunoglobulin levels. Pulmonary involvement occurs in a subset of patients, though the overall prevalence of pulmonary lesions in scleromyxedema is unknown. Since pulmonary hypertension presumably occurs in these patients due to disease progression and development of additional conditions, treatment of the underlying plasma cell dyscrasia and connective tissue disorder may improve pulmonary hypertension symptoms.Case presentationAn elderly patient with scleromyxedema developed pulmonary hypertension refractory to vasodilator and diuretic therapy and subsequently multiple myeloma that responded to a combination therapy of bortezomib, cyclophosphamide, and dexamethasone treatment.ConclusionsTreatment of the underlying disease(s) that contributed to pulmonary hypertension development with anti-neoplastic agents like bortezomib may improve cardiopulmonary symptoms secondary to reducing abnormal blood cell counts and paraprotein levels.

Capecitabine + Epirubicin + Cyclophosphamide Combination Therapy (CEX Therapy) as Neoadjuvant Chemotherapy for HER-2-Negative Breast Cancer: A Retrospective, Single-Center Study.

We modified and administered capecitabine + epirubicin + cyclophosphamide combination therapy (CEX) as neoadjuvant chemotherapy (NAC) for HER-2-negative breast cancer and retrospectively analyzed its effectiveness and tolerability at our center. The inclusion criteria were presence of breast cancer negative for HER-2 and positive lymph node metastasis, or negative lymph node metastasis when tumor diameter was 20 mm or greater without distant metastasis. Additional inclusion criteria were a performance status of 0 or 1, an EF >60%, and an age of 75 years or less. Clinical outcomes were evaluated after 4 courses of epirubicin 80 mg/m2, cyclophosphamide 500 mg/m2 (administered every 3 weeks), and capecitabine 1,500 mg/m2 (administered for 2 weeks and withdrawn for 1 week). A clinical benefit was noted in all 18 patients who received CEX as neoadjuvant chemotherapy during the period from 2009 through 2013. The clinical response rate was 83.3% (15/18), and the clinical complete response rate was 50%. Aesthetic outcomes of breast-conserving surgery were positive in all patients. Among patients with satisfactory outcomes, 33.3% had a pathologic complete response (triple-negative: 6, luminal: 0) and 68.8% were n0 (triple-negative: 8, luminal: 3). All patients with a pathologic complete response are presently alive, free of recurrence, and currently undergoing follow-up. Adverse events were classified as grade 2 or lower in all patients. CEX therapy administered as neoadjuvant chemotherapy could be useful for individualized treatment. In particular, this regimen was effective for triple-negative breast cancer.

Efficacy of Combination Therapy With Pirfenidone and Low-Dose Cyclophosphamide for Refractory Interstitial Lung Disease Associated With Connective Tissue Disease: A Case-Series of Seven Patients

Objectives: This study reports a low dose combination therapy of cyclophosphamide (CYC) and pirfenidone (PFD) and the efficiency and safety of the therapy in refractory connective tissue disease associated interstitial lung disease (CTD-ILD) patients.

Efficacy of Combination Therapy With Pirfenidone and Low-Dose Cyclophosphamide for Refractory Interstitial Lung Disease Associated With Connective Tissue Disease: A Case-Series of Seven Patients.

This study reports a low dose combination therapy of cyclophosphamide (CYC) and pirfenidone (PFD) and the efficiency and safety of the therapy in refractory connective tissue disease associated interstitial lung disease (CTD-ILD) patients. The study included seven CTD-ILD patients (2 males, 5 females; mean age 48.8 years; range, 32 to 63 years) treated between January 2016 and December 2017 in our clinic. At enrolment, all patients had shown no improvement in their symptoms (dyspnea or cough) after at least one month of high dose steroids treatment. Patients who had received adjusted immunosuppressive agents other than steroids or anti-fibrotic medications within the three months before enrolment were excluded. We changed the treatment to a low dose combination of CYC 0.4 g/m2 monthly and PFD 300 mg twice per day and quickly reduced the steroids. All the patients were followed-up for 12 months. Two patients had anti-synthetase syndrome, two had Sjögren syndrome, two had scleroderma and one had mixed connective tissue disease. The baseline forced vital capacity (FVC) was 39-81% and the six-minute walk distance (6MWD) was 202 m-324 m. Within 12 months follow-up, the median improvement in the FVC was 13.4% (range, 0-35.9%), the median improvement of carbon monoxide diffusing capacity was 6.3% (range, 1.7-16%) and the median improvement of 6MWD was 52.7% (range, 34.4-86.3%). All the patients were self-sufficient, and their dyspnea, chest high- resolution computed tomography scores, and quality of life improved simultaneously. Exceeding our expectations, no adverse events associated with CYC or PFD were observed during the follow-up period. Our study provided preliminary while promising clinical evidence for combination therapy of CYC-PFD for CTD-ILD. A low dose combination of CYC and PFD was unexpectedly well tolerated, with satisfactory effects in refractory CTD-ILD patients. Well-designed controlled studies are needed to further establish the safety and efficacy of this approach.

PS1108 CLINICAL FEATURES AND TREATMENT OUTCOMES OF ACQUIRED HEMOPHILIA A IN KOREA: RETROSPECTIVE ANALYSIS

Background:Acquired hemophilia A (AHA) is a rare disease caused by depletion or suppression of coagulation factor FVIII by autoimmune antibodies. Factor VIII inhibitory antibodies neutralize the activity of Factor VIII and, if not properly treated, can lead to life‐threatening hemorrhage or death, with mortality rates as high as 9–22%. There is no report on the incidence and treatment of AHA in Korea. Only a small number of cases have been reported.Aims:The purpose of this study was to evaluate the clinical characteristics and treatment outcome of patients with AHA in Korea.Methods:Patients diagnosed with AHA from January 2006 to May 2016 were enrolled from the 15 institutions in Korea. The diagnostic criteria for AHA were defined as FVIII: C 50% or less and FVIII inhibitory antibody was 0.6 BU/mL or more. A total of 55 patients were enrolled and their medical records were analyzed retrospectivelyResults:Median age was 66 (18–86) years old. In epidemiology, idiopathic was 38% and associated disease was 62%. In epidemiology, 21 patients (38%) were idiopathic and 34 (62%) patients had associated diseases. Associated disease was followed by autoimmune disease (19%), surgery of other disease (13%), infection (13%), pregnancy/postpartum (12%) and hematologic malignancy (12%). The mean FVIII:C activity at diagnosis was 2.69 ± 2.97%, and 14 (26%) patients were less than 1%. The mean titer of FVIII inhibitor was 24.38 ± 34.87 U, and 55 (45%) patients had less than 10 BU. The time from the onset of symptoms to diagnosis was 15.5 (0–100) day, and the time from the first contact with the hematologist to the diagnosis was 3.0 (0–74) day. Overall, the time from symptom onset to diagnosis was relatively long. The sites of bleeding were subcutaneous/skin (83%), muscular (43%), gastrointestinal (21%), mucosal (19%), retroperitoneal (17%), genitourinary (4%), respectively. The severity of bleeding was major in 39 of 55 (71%), and a mean of 14.32 ± 3.332 U red blood cells were transfused per patient who experienced major bleeding.Of the 30 patients who treated for hemostasis, 14 received bypassing agents and 16 received factor VIII concentrates as 1st line hemostatic therapy. The efficacy of the bypassing agent was 86%, which was statistically higher than that of FVIII concentrates (31%) (p &lt;0.05). As immune‐suppressive therapy to eradicate the FVIII antibody, 18 patients (33%) were treated with glucocorticoid alone, and 12 patients (22%) with glucocorticoid and cyclophosphamide combination therapy. The response rate (CR + PR) of glucocorticoid therapy alone was 61%, and the combination of glucocorticoid and cyclophosphamide was 91% (p &lt;0.05). Adverse events were not different between the two groups. The overall survival rate at 1 year was 81.6% and 6 patients died. The causes of death were infection (4 cases) and intracranial hemorrhage (2 cases).Summary/Conclusion:The clinical features of AHA in Korea were not significantly different from the previously published registry data. However, it is considered that the time from symptom onset to diagnosis was relatively long because lack of awareness of AHA. In addition, due to financial problems including national health insurance, only ∼30% of patients were treated with bypassing agent as primary hemostatic therapy. It is necessary to establish more effective treatment strategies in Korea based on the large‐scale prospective analysis of Korean AHA patients.