Comparative efficacy and safety of eleven induction chemotherapy regimens for young adult patients with newly diagnosed acute myeloid leukemia: a network meta-analysis.

The optimal induction chemotherapy regimens for young adult patients with newly diagnosed acute myeloid leukemia (AML) are not well-defined since the lack of direct comparisons between emerging treatments. Network meta-analysis (NMA) is a statistical tool to integrate direct and indirect evidence to evaluate the effect of multiple interventions. Thus, we conducted an NMA to systematically assess the efficacy and safety of different inductions for these patients. PubMed, Embase, Cochrane Library, and Web of Science were searched from establishment to 2020-03-11. Randomized controlled trials (RCTs) using different inductions were included. We deemed 11 trials eligible, including 11 inductions with 5052 participants. Relative risk (RR) and 95% confidence intervals (CIs) were calculated. In terms of complete remission (CR) rate, DAC ranked highest and was significantly higher than IA (RR = 1.27, 95% CI (1.09-1.48)) and DA (RR = 1.28, 95% CI (1.13-1.46)) (p < 0.05). The ranking of DA + Pioglitazone was second only to that of DAC, followed by HAA. For early mortality, HAD, HAA, and DA + GO were significantly higher than DA/IA (p < 0.05). DAC and DA + Pioglitazone showed similar early mortality compared to DA/IA (p > 0.05). Regarding incidence of early grade 3-4 infection, no significant differences between interventions were observed. To conclude, among the included 11 induction regimens, DAC was potentially the top choice for young adult patients with newly diagnosed AML, with highest CR rate, low early mortality, and incidence of early infection. DA + Pioglitazone and HAA also showed a superiority over the others to achieve higher CR rate, while caution should be kept in mind due to the higher early mortality of HAA.

Prognostic value of platelet recovery degree before and after achieving minimal residual disease negative complete remission in acute myeloid leukemia patients.

BACKGROUND: Risk stratification and prognosis prediction of acute myeloid leukemia (AML) are largely dependent on pre-treatment information. However, post-treatment data also provides much useful information. In this retrospective study, we explored whether the level of blood count recovery before and after the first minimal residual disease (MRD) negative complete remission (CR) is relevant to clinical outcomes of AML patients. METHODS: For each included patient, peripheral platelet counts were measured on the day before initial treatment (PLTpre), whereas platelet peak values (PLTpeak) were recorded after marrow recovery following the chemotherapy course inducing the first MRD-negative CR. The difference (DPLT) between these two values (DPLT = PLTpeak-PLTpre) was calculated. X-tile software was utilized to establish the optimal cut-point for DPLT, which was expected to distinguish CR patients with different clinical outcomes. A cross validation analysis was conducted to confirm the robustness of the established cut-point. The results were further tested by a Cox multivariate analysis. RESULTS: The optimal cut-point of DPLT was determined as 212 × 109/L. Patients in high DPLT group were observed to have a significantly better PFS (p = 0.016) and a better OS (without statistical significance, p = 0.106). Cox multivariate analysis showed that higher DPLT was associated with longer PFS (HR = 2.894, 95% CI: 1.320-6.345, p = 0.008) and longer OS (HR = 3.077, 95% CI: 1.130-8.376, p = 0.028). CONCLUSION: Platelet recovery degree before and after achieving MRD-negative CR (DPLT) is a potential predictor of clinical outcomes in CR patients. Higher DPLT value is associated with longer PFS and OS. Our findings may help to develop simple methods for AML prognosis evaluation.

Efficacy and safety of cyclosporine a for patients with steroid-resistant nephrotic syndrome: a meta-analysis.

BACKGROUND: The purpose of this study was to determine efficacy and safety of cyclosporine A (CsA) for patients with steroid-resistant nephrotic syndrome (SRNS). METHODS: The Cochrane Library and PubMed were searched to extract the associated studies on Oct 10, 2018, and the meta-analysis method was used to pool and analyze the applicable investigations included in this study. The P(opulation) I(ntervention) C(omparison) O(utcome) of the study were defined as follows: P: Patients with SRNS; I: treated with CsA, cyclophosphamide (CYC), tacrolimus (TAC) or placebo/not treatment (P/NT); C: CsA vs. placebo/nontreatment (P/NT), CsA vs. CYC, CsA vs. TAC; O: complete remission (CR), total remission (TR; complete or partial remission (PR)), urine erythrocyte number, proteinuria levels, albumin, proteinuria, serum creatinine, and plasma cholesterol, etc. Data were extracted and pooled using RevMan 5.3. RESULTS: In the therapeutic regimen of CsA vs. placebo/nontreatment (P/NT), the results indicated that the CsA group had high values of CR, TR, and low values of proteinuria, serum creatinine, and plasma cholesterol when compared with those in the placebo group. In comparing CsA vs. cyclophosphamide (CYC), the results indicated that the CsA group had higher TR than the CYC group. In comparing CsA vs. tacrolimus (TAC), the results revealed insignificant differences in CR, and TR between the CsA and TAC groups. The safety of CsA was also assessed. The incidence of gum hyperplasia in CsA group was higher than that in the P/NT group, with no differences in incidence of infections or hypertension between CsA and P/NT groups. There was no difference in the incidence of hypertension between the CsA and TAC groups. CONCLUSIONS: CsA is an effective and safe agent in the therapy of patients with SRNS.

Role of follow-up endoscopic examination in treatment response assessment for patients with gastric diffuse large B cell lymphoma.

OBJECTIVE: According to lymphoma guidelines, gastric diffuse large B cell lymphoma (DLBCL) patients should undergo regular computed tomography (CT) and/or positron emission tomography (PET) examinations to assess treatment response. Endoscopic examinations are not indicated in the guidelines. The aim of this study was to investigate the utility of endoscopic examinations during and after treatment for DLBCL. METHODS: We reviewed the patients diagnosed with gastric DLBCL at Seoul St. Mary's Hospital. All patients underwent endoscopy and radiologic examinations at every follow-up appointment. Radiologic response was defined according to World Health Organization criteria and endoscopic response was determined based on the Groupe d'Etude des Lymphomes de l'Adult grading system that is widely used in post-treatment evaluation of gastric MALT lymphoma. RESULTS: Forty-five patients were analyzed. Within a median follow-up period of 34 months, 35 patients achieved both radiologic and endoscopic complete remission (CR). The median times to endoscopic and radiologic CR were not significantly different (21 versus 16 weeks, p = 0.118). However, in 25 patients with stage I disease, endoscopic CR [median (range), 20 (11-36)] was achieved later than radiologic CR [median (range), 13 (8-36)] (p = 0.027). Among 40 patients who achieved radiologic CR, 35 patients who also achieved endoscopic CR maintained remission during the follow-up. Two of the five patients who achieved radiologic CR without endoscopic CR experienced recurrence. CONCLUSIONS: In gastric DLBCL patients, endoscopic response does not always correlate with radiologic response and might predict disease recurrence. We suggest that follow-up endoscopic examination with biopsy should be performed in addition to radiologic examination.

Current Strategy for the Treatment of Ovarian Germ Cell Tumors: Role of Extensive Surgery.

OPINION STATEMENT: The necessity and extent of comprehensive surgical staging (CSS) and lymphadenectomy in the treatment of malignant ovarian germ cell tumors (MOGCTs) is still controversial. However, it is uniformly agreed that CSS with lymphadenectomy is crucial to follow up patients without adjuvant chemotherapy in stage I MOGCTs. Considering the chemotherapy-sensitive nature of MOGCTs, fertility-sparing cytoreductive surgery (FSCS) seems a reasonable approach in initial treatment for patients with advanced stage. When encountered with bilateral MOGCTs, debulking is surely granted if there is no desire for fertility. Both ovaries completely replaced by neoplastic tissue composed the most challenging situation especially when patients require childbearing potential. In dysgerminoma histology, which usually has good prognosis, residual disease could be left to spare fertility. USO of the largest and more heterogeneous ovarian mass and a biopsy of the contralateral lesion may be considered if the patients are compliant to regular follow-up. NACT followed by interval FSCS may be a reasonable option in patients with extensive disease, when initial debulking is not an option or where the poor general condition or clinical findings suggest an increased risk of surgical morbidity or preclude fertility-sparing surgery. This is currently not the standard of care but deserves future study. In some rare situation, when any remaining ovarian tissue means high risk, BSO may be performed with the uterus preserved for possible assisted reproduction with donor egg. Treatment failure occurs in a small group of MOGCTs after primary treatment. A good number of recurrences can be salvaged with selected salvage surgery, especially when optimal secondary cytoreduction can be achieved. Immature teratoma is a subtype of MOGCTs where secondary cytoreduction may have a strong role to play.

Real-Life Management of FLT3-Mutated AML: Single-Centre Experience over 24 Years.

We analyzed 140 patients with a median age of 51 years; 21% had WBC ≥ 100 × 109/L, and 52% had an NPM1 co-mutation. Until 2018, 101 patients received chemotherapy; thereafter, 39 received 3+7+midostaurin. The overall CR rate was 64%, higher in NPM1 mutant patients (73%). Univariate analysis showed that NPM1 mutation (p = 0.032) and WBC < 100 × 109/L (p = 0.013) positively influenced the response, with a trend for FLT3i administration (p = 0.052). Multivariate analysis confirmed WBC count as an independent prognostic factor (p = 0.017). In CR1, 41/90 patients underwent allogeneic and 18 autologous transplantation. The median EFS was 1.1 vs. 1.6 years in autografted and allografted patients, respectively (p = 0.9). The one-year non-relapse mortality was 0.00% for autologous and 28% for allogeneic transplants (p = 0.007); CIR at 1 and 3 years was higher in autologous transplants (39% vs. 15% and 57% vs. 21%, p = 0.004). The median survival was not reached in the FLT3i group. Overall, 69 patients received stem cell transplantation (18 autologous, 51 allogeneic). Post-transplant FLT3i was resumed in eight patients, all alive after a median of 65 months. Allogeneic transplantation is crucial in FLT3-mutated AML, but the next challenge will be to identify which patients can benefit from transplants in CR1 and in which to intensify post-transplant therapy.

Spontaneous remission of acute lymphoblastic leukemia: A series of nine cases and a review of literature.

AIMS: To report a series of acute lymphoblastic leukemia (ALL) cases with spontaneous remission and provide presenting clinical and pathologic information and details of clinical course to raise awareness among oncologists and patients. METHODS: We identified and analyzed nine patients with ALL and spontaneous remission. Review of literature reveals an additional nine previously reported cases with similar clinical course. RESULTS: All of these patients, ranging in age from 2 to 12 years of age, presented with inciting signs and symptoms of viral or bacterial infection. All of the patients showed varying percentages of lymphoblasts (.2% to 90%) in diagnostic bone marrow biopsy. All B-ALL cases shared a similar blast phenotype on flow cytometry with coexpression of CD19, CD10 and TdT and variable CD20 expression. All nine patients achieved spontaneous remission of their leukemia as confirmed by flow cytometry and/or bone marrow biopsy without chemotherapeutic intervention. Time to remission from presentation ranged from 1 to 8 weeks. After remission, all patients redeveloped ALL, and time from remission to reemergence ranged from 2 to 24 weeks. CONCLUSION: Our series of cases and cases identified in literature show that ALL diagnosed with modern methods of flow cytometry and molecular analysis will recur within weeks to months from disappearance, usually with cytopenias, which provides a template for oncologic follow-up and testing in these patients.

G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Acute Leukemia Patients in the First Complete Remission: A Registered Study.

G-CSF-mobilized peripheral blood (G-PB) harvest is the predominant graft for identical sibling donor and unrelated donor allogeneic hematopoietic stem cell transplantation (HSCT) recipients, but it was controversial in haploidentical related donor (HID) HSCT. In this registry study, we aimed to identify the efficacy of HID G-PB HSCT (HID-PBSCT) for acute leukemia (AL) patients in first complete remission (CR1). Also, we reported the outcomes for the use of G-PB grafts in comparison with the combination of G-BM and G-PB grafts in HID HSCT recipients. Sixty-seven AL patients in CR1 who received HID-PBSCT were recruited at Institute of Hematology, Peking University. Patients who received haploidentical HSCT using the combination of G-BM and G-PB harvests in the same period were enrolled as controls (n=392). The median time from HSCT to neutrophil and platelet engraftment was 12 days (range, 9-19 days) and 12 days (range, 8-171 days), respectively. The 28-day cumulative incidence of neutrophil and platelet engraftment after HSCT was 98.5% and 95.5%, respectively. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 29.9% (95%CI 18.8-40.9%) and 7.5% (95%CI 1.1-13.8%), respectively. The cumulative incidences of total and moderate-severe chronic GVHD were 54.9% (95%CI 40.9-68.8%) and 17.4% (95%CI 6.7-28.0%), respectively. The cumulative incidences of relapse and non-relapse mortality were 13.9% (95%CI 5.4-22.5%) and 3.4% (95%CI 0-8.1%), respectively. The probabilities of overall survival (OS) and leukemia-free survival (LFS) were 84.7% (95%CI 74.7-94.7%) and 82.7% (95%CI 73.3-92.1%) respectively. Compared with the HID HSCT recipients using the combination of G-BM and G-PB grafts, the engraftments of neutrophil and platelet were both significantly faster for the G-PB group, and the other clinical outcomes were all comparable between the groups. In multivariate analysis, graft types did not influence the clinical outcomes. Overall, for the patients with AL CR1, G-PB graft could be considered an acceptable graft for HID HSCT recipients. This study was registered at https://clinicaltrials.gov as NCT03756675.

The effect of 5-Aminolaevulinic Acid Photodynamic Therapy versus CO2 laser in the Treatment of Cervical Low-grade Squamous Intraepithelial Lesions with High-Risk HPV Infection: A non-randomized, controlled pilot study.

BACKGROUND: There are insufficient studies comparing the efficacy of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) against CO2 laser therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with high-risk human papillomavirus (HR-HPV), especially for long-term efficacy. METHODS: Patients with cervical LSIL and HR-HPV infection were divided into two treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4-6 months and 12 months after the treatment. RESULTS: (1) Among 277 patients, 176 patients received 5-ALA PDT and 101 patients received CO2 laser therapy. (2) 4-6 months after treatment, there was no significant difference between two groups in the complete remission (CR) rates of cervical LSIL and the clearance rate of HR-HPV infection. (3) 12 months after treatment, compared with the CO2 laser group, the CR rates of cervical LSIL in the 5-ALA PDT group was significantly higher than the CO2 laser group. There was no statistical difference in the clearance rate of HR-HPV infection between the two groups. (4) 12 months after treatment, the recurrence rate of cervical lesions and the reinfection rate of HR-HPV infection in 5-ALA PDT group were significantly lower than those in CO2 laser group. CONCLUSION: The effect of 5-ALA PDT is similar to CO2 laser at 4-6 months. The long-term efficacy of 5-ALA PDT appears better than CO2 laser. As a non-invasive treatment, 5-ALA PDT is a highly effective therapeutic procedure for cervical LSIL with HR-HPV infection.

Complete remission in a patient with advanced renal pelvis carcinoma with lung metastasis treated with durvalumab immunotherapy: a case report.

For early-stage upper urothelial carcinoma, total nephroureterectomy combined with bladder sleeve resection is the standard treatment. However, for patients with advanced disease, there is a lack of effective therapeutic strategies. In recent years, with an increased understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibition has been explored and clinically used in the area of urothelial carcinoma. The programmed cell death 1 receptor (PD-1) and its ligand (PD-L1) are important negative regulators of immune activity, preventing the destruction of normal tissues and autoimmunity. Nowadays, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US FDA) for the first- or second-line use in urothelial carcinoma, based on durable response and manageable safety profiles observed in relevant clinical trials. In this study, we present the case of a 64-year-old patient with renal pelvis carcinoma who went on to develop lung metastasis after postoperative chemotherapy. CT scan showed multiple scattered solid small nodule foci in both lungs (considered as metastasis). The patient received immunotherapy with PD-L1 monoclonal antibody (Durvalumab) alone, and achieved complete remission (CR) after 3 cycles of treatment. During the treatment, slight weakness was reported, and no nausea, fever and other adverse events were observed. This case shows that durvalumab could effectively and safely treat a case of renal pelvis carcinoma with lung metastases.

PD1 expression on bone marrow T-cells in newly diagnosed Egyptian AML patients: Correlation with hematological parameters, aberrant antigens expression, and response to induction therapy.

Background: Programed cell death protein 1 (PD-1) is a key mediator for the development of T cell exhaustion that develops in response to persistent antigen stimulation. Aim: In this study, we measured PD1 expression on CD3 positive bone marrow T-lymphocytes in newly diagnosis AML patients and its relation to clinical/ prognostic outcomes in addition to response to induction therapy (day 28). Methods: This study was conducted on 59 newly diagnosed AML patients and 20 healthy controls. Complete blood counts, flow cytometry using acute leukemia panel in addition to PD1 monoclonal antibodies were performed on bone marrow lymphocytes (CD3+), whereas cytogenetic/molecular studies were used to determine risk group. The patients' remission status following induction therapy was determined. Results: PD1 was brightly expressed in 91.5% of the cases than control sample with highly significant difference (P = .001). A cutoff of 3.5 for mean fluorescence intensity was used to divide patients into two groups (higher vs normal PD1 expression). A significant difference between the two groups regarding platelet count and aberrant CD7 expression (P = .007 and .023, respectively) was found. Those normally expressed PD1 respond better to induction therapy. Conclusion: PD1 expression on BM T-cells had a predictive value and providing an immunotherapeutic target for AML.

Efficacy and safety of tacrolimus vs cyclophosphamide in the therapy of patients with idiopathic membranous nephropathy: a meta-analysis.

BACKGROUND: As one of the therapeutic drugs for idiopathic membranous nephropathy (IMN), tacrolimus (TAC) has not been fully vindicated for its efficacy and tolerability. A meta-analysis was performed to detect the efficacy and safety of TAC plus glucocorticoid vs cyclophosphamide (CTX) plus glucocorticoid in therapy of patients with IMN. METHODS: A literature search with a pre-defined search strategy was conducted using English databases (PubMed, EMBASE, ClinicalKey and the Cochrane Library) and Chinese databases (China National Knowledge International, Wanfang, Chinese Scientific Journal Database (VIP)) from inception to Nov 19, 2018. Any high-quality randomized controlled trials (RCTs) comparing the effectiveness or safety of TAC with CTX in IMN patients were included. Data were extracted by two authors independently and analyzed using RevMan 5.3. RESULTS: Four randomized controlled studies were included. In this analysis, we did not find that the statistically significant difference between TAC and CTX groups on 6-month and 12-month treatment complete remission (CR) was evident (6-month: OR=1.53, 95% CI: 0.85-2.76, P=0.15; 12-month: OR=2.17, 95% CI: 0.56-8.44, P=0.27). But TAC had better 6-month total remission (TR; total CR plus partial remission [PR]) than CTX (6-month: OR=2.62, 95% CI: 1.38-4.96, P=0.003; 12-month: OR=1.74, 95% CI: 0.29-10.48, P=0.54), and got a lower proteinuria after 6-month treatment (OR=-0.80, 95% CI: -1.53 to -0.07, P=0.03). TAC had a lower incidence rate on leucopenia than CTX, but had a tendency towards higher blood creatinine. In the meantime, tremor in TAC group was higher than that in CTX group. The differences on other adverse effects such as gastrointestinal syndrome, infection, herpes zoster, hypertension, liver function disorder and hyperglycemia were also analyzed. However, none of them were statistically significant. CONCLUSION: TAC treatment could get high value of TR and had low value of proteinuria level when compared with those in CTX on 6-month treatment in therapy of patients with IMN.

Lymph Node Metastasis From Gastroesophageal Cancer Successfully Treated by Nivolumab: A Case Report of a Young Patient.

Background: Immuno-oncology is a novel target of cancer therapy. Nivolumab is a monoclonal anti-programed death-1 antibody recently used to treat patients with chemotherapy-resistant gastric and gastroesophageal cancer. Although the disease control rate is reported to be very high, few cases demonstrate a complete response. Case Presentation: A 25-year-old man diagnosed with gastroesophageal cancer was treated with chemotherapy followed by surgical resection. Pathological diagnosis was poorly differentiated adenocarcinoma with distant lymph node metastasis. Residual lymph node metastasis was treated with nivolumab monotherapy, resulting in complete disappearance. No recurrence has been observed for 2 years since discontinuation of nivolumab. This rare case was additionally subjected to pathological and genetic analysis, suggesting that a high tumor mutation burden (10.7 mutations/Mb) might be associated with sensitivity to nivolumab. Summary: We reported a case of advanced gastroesophageal junction cancer with distal lymph node metastasis that was successfully treated with chemotherapy, surgical resection, and nivolumab therapy. An aggressive search for biomarkers implying benefit effects of nivolumab should be performed.