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Recent evidence has indicated that measurable residual disease (MRD) markedly affects the prognosis of patients with acute leukemia post-transplantation. However, the prognostic relevance of complete remission with incomplete count recovery (CRi) before transplantation has not been extensively explored. In this single-center, longitudinal study, we assessed the outcomes of 466 MRD-negative acute leukemia patients who underwent single-unit unrelated cord blood transplantation (sUCBT), including 117 patients with CRi. We observed that acute myeloid leukemia (AML) patients with CRi had a significantly lower cumulative incidence of both neutrophil (90.8% versus 96.5%) and platelet engraftment (67.2% versus 85.3%) and experienced increased transplant-related mortality (TRM) (100-day TRM: 14.2% versus 5.3%; 1-year TRM: 20.6% versus 11.3%; P = .024 and .063, respectively), mainly due to infection-related deaths, compared to those in complete remission (CR). Multivariate analysis revealed that CRi was an independent adverse predictor of both neutrophil and platelet engraftment and increased 100-day TRM in AML patients. However, CRi status did not affect relapse or reduce 5-year overall survival (OS), leukemia-free survival (LFS), or GVHD-free relapse-free survival (GRFS) in the AML cohort. Conversely, for patients with acute lymphoblastic leukemia (ALL), CRi did not impact engraftment, TRM, relapse or survival after sUCBT. Our findings underscore that CRi status before sUCBT portends poorer engraftment outcomes and a greater TRM in AML patients, although it does not significantly affect the prognosis of ALL patients., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe the natural history of AML, the clinical results and the need for treatment during long-term follow-up of renal AML., Methods: Retrospective study of patients diagnosed with AML by computed tomography or nuclear magnetic resonance between 2001 and 2019, with at least two follow-up images. Clinical and imaging variables, need for intervention, complications and follow-up time were recorded. Statistical analysis was performed using SPSS 22.0., Results: 111 patients and 145 AML were included. The median follow-up was 6.17 years (range 0.7-18.1, IQR 11.8-12.2). The median tumor size at diagnosis was 13 mm (IQR 7.5-30), with 24 (16.4%) being ≥ 4 cm. Most presented as an incidental finding (85.5%); in 3 (2.1%) cases, the presentation was as a spontaneous retroperitoneal hematoma. The main indication for intervention was size ≥ 4 cm in 50%. Eighteen (12%) patients received a first intervention, being urgent in 3. Embolization was performed in 15 cases and partial nephrectomy in 3. The need for reintervention was recorded in five: two underwent partial nephrectomy and two total nephrectomy; one patient required a new urgent embolization. Of the non-operated patients, 43% decreased in size or did not change, while 57% increased, with the median annual growth being 0.13 mm (IQR - 0.11 to 0.73). There were no differences in the median growth in tumors measuring ≥ 4 cm (0.16 mm) at diagnosis vs. < 4 cm (0.13 mm) (p = 0.9)., Conclusions: The findings of this study suggest that AML typically demonstrate a slow-progressing clinical course during long-term follow-up. Moreover, our observations, which cast doubt on tumor size as a reliable predictor of adverse clinical outcomes, advocate for a less intensive monitoring strategy in both monitoring frequency and choice of imaging modality., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

BACKGROUND In t(8;21) acute myeloid leukemia (AML), patients with extramedullary infiltration (EMI) tend to have worse survival outcomes than those without EMI. However, it is still unclear whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefits EMI-positive t(8;21) AML patients. MATERIAL AND METHODS This study retrospectively enrolled 651 t(8;21) AML patients, and analyzed 51 patients with EMI at diagnosis. Among the 51 patients, 15 patients received allo-HSCT. RESULTS The incidence of EMI in t(8;21) AML was 10.0%, and the first complete remission rate was 78.5% in EMI-positive t(8;21) AML patients. The central nervous system was the most frequently involved site (29.4%), followed by bones (15.7%), and skin (9.8%). In terms of karyotype, 19 (37.3%) patients were t(8;21) alone, 12 (23.5%) had additional loss of a sex chromosome, and 5 (9.8%) had complex karyotype. Significantly better overall survival was observed in patients with allo-HSCT compared to patients without allo-HSCT in both multivariable models (HR=0.32; P=0.0122) and the Kaplan-Meier curves (P=0.0157). CONCLUSIONS Allo-HSCT improved the survival of EMI-positive t(8;21) AML.

Although alternative donors extend transplant access, whether recipient ancestry affects the time to allogeneic transplant is not established. We analyzed the likelihood of clinically significant delays to allograft by patient ancestry in 313 adult patients with acute myelogenous leukemia (AML) who underwent transplantation. Non-European ancestry patients (n = 99) were more likely than Europeans (n = 214) to receive HLA-mismatched donor allografts (45% vs 24%). Overall, the median time from transplant indication to allograft was 127 days (range, 57-1683). In multivariable analysis, non-Europeans had an increased risk of prolonged indication to transplant time >180 days owing to significant delays in indication to consult >90 days and consult to transplant >120 days. Compared with recipients of HLA-matched unrelated donors (URDs), HLA-mismatched adult donor recipients were at an increased risk of delayed indication to transplant, whereas HLA-identical sibling and cord blood recipients were at a lower risk. Subanalysis showed more indication to transplant delays >180 days in non-European (44%) vs European (19%) 8/8 URD recipients. Finally, the pandemic further exacerbated delays for non-Europeans. In summary, although non-European patients with AML are less likely to receive 8/8 URDs as expected, if they do, their transplants are delayed. HLA-identical siblings and cord blood facilitate the fastest transplants regardless of patient ancestry, whereas other adult donor transplants are delayed. Strategies to mitigate referral barriers, hasten donor evaluation, and use all alternative donor sources are critical to ensure timely transplantation for patients with AML., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Recent developments in chemotherapy for gynecologic malignancies have improved treatment results in patients and promoted long-term survival. However, various adverse events caused by long-term chemotherapy are still being observed. Here, we report a case of myelodysplastic syndrome that developed during chemotherapy for recurrent ovarian cancer and progressed to acute myeloid leukemia. However, chemotherapy for ovarian cancer was continued while maintaining the quality of life under certain conditions, such as maintenance of platelet levels in collaboration with a hematologist. A 69- year-old woman(gravida 3, para 2)was diagnosed with stage ⅢC ovarian cancer in our department. After 6 cycles of preoperative chemotherapy with paclitaxel plus carboplatin plus bevacizumab(TC plus Bev), we performed a simple abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, sigmoid colon resection, and low anterior resection. Postoperatively, 3 cycles of TC plus Bev and 6 cycles of Bev monotherapy were completed for stage ⅢC ovarian cancer (ypT3cNXM0, high-grade serous carcinoma). However, the cancer recurred, and the patient received 3 cycles of gemcitabine plus Bev and 3 cycles of doxorubicin plus Bev. Precursor cells and prolonged neutropenia were observed, and myelodysplastic syndrome was diagnosed. One month later, the condition progressed to acute myeloid leukemia. The patient's neutrophil count recovered spontaneously, and subsequently, 7 cycles of weekly paclitaxel plus Bev therapy were completed along with symptomatic treatment. Unfortunately, she died of septic shock against the background of acute myeloid leukemia. It is important to monitor the appearance of blasts for early detection of therapy-related myelodysplastic syndromes occurring during chemotherapy, as in the case in this report. Additionally, it is important to maintain platelet count and continue chemotherapy for the primary disease.

Pulmonary complications may occur after hematopoietic stem cell transplantation for hematologic malignancies. Lung transplantation is the only treatment option for end-stage lung failure. We presented a case of acute myeloid leukemia who received a hematopoietic stem cell transplantation and underwent bilateral lung transplantation with end-stage usual interstitial pneumonia and chronic obstructive lung disease. This case showed that lung transplantation could be successfully applied in properly selected hematologic malignancy patients with long disease-free survival, like lung transplantations performed for other indications., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Angiomyolipomas (AML) represent less than 10% of renal tumours. They are most often detected incidentally during imaging tests, but there are several histological variants that pose difficulties in the radiological differential diagnosis. Their identification should allow the loss of renal parenchyma due to embolization or radical surgery to be prevented., Methods: Retrospective study of patients undergoing kidney surgery with post-surgical pathological diagnosis of AML at the Álvaro Cunqueiro Hospital (2016-2021). Patients with a radiological diagnosis of AML who underwent surgery based on clinical criteria were excluded., Results: 18 patients were registered, allowing for the assessment of 18 renal tumours. All of the cases were diagnosed incidentally. Preoperative radiological diagnosis was: 9 lesions suggestive of renal cell carcinoma (RCC) (50%), 7 cases suggestive of RCC vs. AML (38.9%) and 2 lesions suggestive of AML vs. retroperitoneal liposarcoma (11.1%). Histological variants of AML were found in 61.1% of cases (n = 11). The most widely used surgical technique was partial nephrectomy, in 66.67% of cases., Conclusions: The radiological differential diagnosis of AML, and particularly its variants, with malignant lesions have important limitations either due to the predominance or scarcity of any of the AML components. Some cases can also pose difficulties at the histological level. This fact highlights the importance of the specialization of uroradiologists and uropathologists and the performance of kidney-sparing therapeutic techniques.

An 18-year-old girl with high-risk acute myeloid leukemia developed Streptococcus mitis septic shock and multiorgan dysfunction syndrome, including biventricular failure. Due to the anticipated reversibility of her cardiogenic shock, her young age, and her favorable survival chance after an allogeneic hematopoietic stem cell transplant, she was placed on full circulatory support with venoarterial extracorporeal membrane oxygenation as a bridge to her successful hematopoietic stem cell transplantation 2 months later. This highlights the importance of prognostication in patient selection for extracorporeal life support. A multidisciplinary approach is essential to each case until more definite initiation criteria, risk stratification, and treatment protocols are established., Competing Interests: The authors declare no conflict of interest, (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the preferred treatment for children with high-risk hematologic malignancies, but post-allo-HSCT relapse has a poor prognosis and limited treatment options. We evaluated the feasibility, outcome, and risk factors influencing survival after T-cell-replete haploidentical HSCT with low-dose anti-thymocyte globulin (ATG) in 30 patients with post-allo-HSCT relapse of acute lymphoblastic leukemia and acute myeloid leukemia. Overall, 50% of the patients had complete remission (CR) before the second transplant and the overall survival (OS) rate was 52%. In surviving patients (median follow-up 614 days), Kaplan-Meier analysis revealed estimated 2-year leukemia-free survival and OS rates of 48.1% and 61.1%, respectively. Cumulative incidences of 2-year non-relapse mortality and relapse were 24.7% and 36.3%, respectively. Achieving CR before the second allo-HSCT was a predominant independent prognostic factor identified in the multivariate analysis, with a significantly improved 2-year OS rate of 86.7%. T-cell-replete haplo-HSCT with low-dose ATG for second allo-HSCT may benefit a selected patient population., (© 2021. Japanese Society of Hematology.)

The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56 months (range 22-108 months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25 mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging., (© 2021. Japanese Society of Hematology.)

Background: The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation., Methods: We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People's Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study., Results: The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD < 1.0% groups (3-year CIR: 75% ± 15.3% vs. 0%, P < 0.001; 3-year OS: 25.0 ± 15.3% vs. 80.7% ± 6.6%, P < 0.001; 3-year DFS: 25.0 ± 15.3% vs. 80.7 ± 6.6%, P < 0.001; 3-year TRM: 0 vs. 19.3 ± 6.6%, P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD < 1% before transplantation has no significant difference on the prognosis., Conclusions: Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse., (© 2021. The Author(s).)

Angiomyolipomas (AMLs) are mesenchymal tumours derived from perivascular epithelioid cells. Although AMLs are generally known as benign and extremely rare epithelioid variants of AML, they may be potentially aggressive. Here we present an adrenal epithelioid AML and the literature review. A 64-year-old female patient was diagnosed with a left adrenal mass detected incidentally on ultrasonography. Preoperative abdominal CT (computed tomography) showed a 95×68 mm heterogeneous contrast enhancement mass lesion in the left adrenal gland. The lesion was hormone inactive in the endocrinological evaluation, and left laparoscopic adrenalectomy was performed. The patient was discharged on the 2nd postoperative day. Pathology was reported as epithelioid subtype AML. The patient has no local recurrence or metastasis in the 18-month follow-up period and imaging. Adrenal epithelioid AML is an extremely rare and potentially aggressive variant. According to the literature, open or laparoscopic adrenalectomy seems to be suitable option for disease management.

We present a case of acute myeloid leukemia developing acute graft-versus-host-disease (GVHD) in the post transplant phase. The patient had GVHD of skin, liver and gastro-intestinal tract (resolved) with polymicrobial sepsis. The clinical course, treatment and pathological findings on autopsy including the cause of death have been discussed.

Purpose: The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source., Experimental Design: We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia ( n = 6,548) between 2007 and 2017 using a Japanese database. In all analyses, we separately evaluated three distinct cohorts based on donor type [(8/8 allele-matched sibling donor, 8/8 allele-matched unrelated donor, and unrelated single-cord blood (UCB)]., Results: The multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, showed a reductive effect of grade I-II acute GVHD on treatment failure (defined as 1-leukemia-free survival; P < 0.001), overall mortality (OM; P < 0.001), relapse ( P < 0.001), and non-relapse mortality (NRM; P < 0.001) in patients receiving from UCB. A reductive effect of limited chronic GVHD on treatment failure ( P < 0.001), OM ( P < 0.001), and NRM ( P < 0.001) was also shown in patients receiving from UCB. However, these effects were not always shown in patients receiving from other donors. The beneficial effects of mild acute and chronic GVHD after UCB transplantation on treatment failure were noted relatively in subgroups of patients with acute myelogenous leukemia and a non-remission status., Conclusions: These data suggested that the development of mild GVHD could improve survival after UCB transplantation for acute leukemia., (©2021 American Association for Cancer Research.)

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are usually associated with poor outcomes, especially in high-risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for patients suffering from high-risk AML/MDS. However, many patients relapse after allo-HSCT. Novel therapy to prevent relapse is urgently needed. Both the BCL-2 inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration of DEC has been shown to ameliorate graft-versus-host disease (GVHD) and boost the graft-versus-leukemia (GVL) effect post-transplantation. We therefore conducted a prospective study (ChiCTR1900025374) to examine the tolerability and efficacy of a maintenance therapy of low-dose decitabine (LDEC) plus VEN to prevent relapse after allo-HSCT for high-risk AML/MDS patients. Twenty patients with high-risk AML (n = 17) or high-risk MDS (n = 3) post-transplantation were recruited. Approximately day 100 post-transplantation, all patients received LDEC (15 mg/m 2 for 3 d) followed by VEN (200 mg) on d 1-21. The cycle interval was 2 mo, and there was 10 cycles. The primary end points of this study were rates of overall survival (OS) and event-free survival (EFS). The secondary endpoints included adverse events (AEs), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD), and incidences of viral infection after allo-HSCT. Survival outcomes were assessed using Kaplan-Meier analysis. The median follow-up was 598 (149-1072) d. Two patients relapsed, 1 died, and 1 is still alive after the second transplant. The 2-y OS and EFS rates were 85.2% and 84.7%, respectively. The median 2-y EFS time was 525 (149-1072) d, and 17 patients still had EFS and were alive at the time of this writing. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 AEs were observed in 35% (7/20) and 20% (4/20) of the patients, respectively. No grade >3 AEs were observed. aGVHD (any grade) and cGVHD (limited or extensive) occurred in 55% and 20% of patients, respectively. We conclude that LDEC + VEN can be administered safely after allo-HSCT with no evidence of an increased incidence of GVHD, and this combination decreases the relapse rate in high-risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent relapse in high-risk AML/MDS patients., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose of Review: With the recent approval of multiple new drugs for the treatment of acute myeloid leukemia (AML), the relevance of conventional treatment approaches, such as daunorubicin and cytarabine ("3+7") induction chemotherapy, has been challenged. We review the AML risk stratification, the efficacy of the newly approved drugs, and the role of "3+7"., Recent Findings: Treatment of AML is becoming more niched with specific subtypes more appropriately treated with gemtuzumab, midostaurin, and CPX-351. Although lower intensity therapies can yield high response rates, they are less efficient at preventing relapses. The only curative potential for poor-risk AML is still an allogeneic stem cell transplant. The number of AML subtypes where 3+7 alone is an appropriate therapeutic option is shrinking. However, it remains the backbone for combination therapy with newer agents in patients suitable for intensive chemotherapy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Acute myeloid leukemia (AML) is a hematological malignancy originating from myeloid precursor cells, with different cytogenetic abnormalities, genetic mutations and diverse clinical prognoses. We investigated the clinical characteristics, treatment patterns, and outcomes of adult AML patients in Taiwan., Materials and Methods: We retrospectively included 3851 patients with AML in the Taiwan Cancer Registry Database from 2011 to 2015. We excluded patients younger than 20 years, with acute promyelocytic leukemia, and with no pathological confirmation., Results: Among the 3292 patients included, 2179 received induction chemotherapy and 1113 did not, because of older age and higher Charlson comorbidity index (CCI) score. Among the 2179 treated patients, 162 received high-dose cytarabine-based chemotherapy, 1535 received standard-dose cytarabine with anthracyclines, 209 received low-dose cytarabine-based chemotherapy, and 273 received chemotherapy without cytarabine. Patients in the low-dose cytarabine group had the oldest age and highest CCI scores compared with the other groups. In the analysis of overall survival (OS), the median OS of the overall study population was 6.27 months. Treated patients with AML had a longer OS than untreated ones (12.43 months treated vs. 2.03 months not treated; P < .0001). In the multivariate analyses of the treated patients with AML, several factors indicated better prognosis, including receiving standard-dose or high-dose cytarabine, female sex, younger age, lower CCI score, treatment at a medical center, favorable cytogenetic abnormalities, and allogeneic hematopoietic stem cell transplantation., Conclusion: Our study was a population-based study that illustrates the real-world outcomes of adult patients with AML in Taiwan., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Despite the ability of combination antiretroviral therapy (cART) to increase the life expectancy of patients infected with human immunodeficiency virus (HIV), viral reservoirs persist during life-long treatment. Notably, two cases of functional cure for HIV have been reported and are known as the "Berlin Patient" and the "London Patient". Both patients received allogeneic hematopoietic stem cell transplantation from donors with homozygous CCR5 delta 32 mutation for an associated hematological malignancy. Therefore, there is growing interest in creating an HIV-resistant immune system through the use of gene-modified autologous hematopoietic stem cells with non-functional CCR5 . Moreover, studies in CXCR4 -targeted gene therapy for HIV have also shown great promise. Developing a cure for HIV infection remains a high priority. In this review, we discuss the increasing progress of coreceptor-based hematopoietic stem cell gene therapy, cART, milder conditioning regimens, and shock and kill strategies that have important implications for designing potential strategies aiming to achieve a functional cure for the majority of people with HIV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ding, Liu and Lai.)

Background: The optimal conditioning regimen in cord blood transplantation (CBT) needs to be determined. This study aimed to identify the impact of conditioning regimen on the outcome of CBT in children with acute leukemia., Methods: Medical records of patients with acute leukemia who received CBT were retrospectively reviewed., Results: A total of 71 patients were allocated into 2 groups; patients who received total body irradiation 10 Gy, cyclophosphamide 120 mg/kg, and fludarabine 75 mg/m² were named as TCF group (n = 18), while the non-TCF group (n = 53) included patients conditioned with regimens other than the TCF regimen. All patients in the TCF group were successfully engrafted, while 22.6% in the non-TCF group (n = 12) failed to achieve donor-origin hematopoiesis ( P = 0.028). The incidence of cytomegalovirus diseases was 5.6% in the TCF group and 30.2% in the non-TCF group ( P = 0.029). The 5-year overall survival rates of the TCF and non-TCF groups were 77.8% and 44.2%, respectively ( P = 0.017)., Conclusion: Patients conditioned with the TCF regimen achieved better engraftment and survival rates, less suffering from cytomegalovirus disease. Our data suggest that the TCF regimen is a preferred option for CBT in children with acute leukemia., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background: Survivors of childhood acute myeloid leukemia (AML) are vulnerable to medical late effects of treatment; however, less is known about their psychosocial outcomes. This study evaluated neurocognitive and psychosocial outcomes in long-term AML survivors treated with bone marrow transplantation (BMT) or intensive chemotherapy (IC) without BMT., Methods: AML survivors (N = 482; median age at diagnosis = 8 [range = 0-20] years; median age at evaluation = 30 [range = 18-49] years) treated with BMT (n = 183) or IC (n = 299) and sibling controls (N = 3190; median age at evaluation = 32 [range = 18-58] years) from the Childhood Cancer Survivor Study were compared on emotional distress (Brief Symptom Inventory-18), neurocognitive problems (Childhood Cancer Survivor Study Neurocognitive Questionnaire), health-related quality of life (SF-36), and social attainment. Outcomes were dichotomized (impaired vs nonimpaired) using established criteria, and relative risks (RRs) were estimated with multivariable Poisson regression, adjusted for age at evaluation and sex., Results: AML survivors were more likely than siblings to report impairment in overall emotional (RR = 2.19, 95% confidence interval [CI] = 1.51 to 3.18), neurocognitive (RR = 2.03, 95% CI = 1.47 to 2.79), and physical quality of life (RR = 2.71, 95% CI = 1.61 to 4.56) outcomes. Survivors were at increased risk for lower education (RR = 1.15, 95% CI = 1.03 to 1.30), unemployment (RR = 1.41, 95% CI = 1.16 to 1.71), lower income (RR = 1.39, 95% CI = 1.17 to 1.65), and not being married or having a partner (RR = 1.33, 95% CI = 1.17 to 1.51). BMT-treated survivors did not differ statistically significantly from IC-treated on any outcome measure., Conclusions: AML survivors are at increased risk for psychosocial impairment compared with siblings; however, BMT does not confer additional risk for psychosocial late effects compared with treatment without BMT., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Opinion Statement: The treatment of acute myeloid leukemia (AML) has evolved considerably over the past several years. Advances in the field have historically benefited younger patients; however, a growing understanding of the molecular basis of leukemogenesis has brought multiple targeted agents to the clinic for patients of all ages. These therapies have expanded the therapeutic landscape for elderly patients from more than best supportive care and low-intensity monotherapy. In general, we currently utilize a backbone regimen of a hypomethylating agent (HMA) or low-intensity chemotherapy with the BCL-2 inhibitor venetoclax for the majority of elderly patients with newly diagnosed AML. For patients with targetable mutations, we employ a doublet/triplet strategy of HMA + a targeted inhibitor +/- venetoclax, often in the context of a clinical trial. CPX-351 is reserved for patients with secondary or therapy-related AML. In this review, we will outline our approach to the treatment of elderly patients with AML, with particular emphasis on recently approved agents and emerging novel therapies.

Hypomethylating agents (HMA) with venetoclax is a new standard for older/unfit patients with acute myeloid leukemia (AML). However, it is unknown how HMA with venetoclax compare to intensive chemotherapy (IC) in patients who are "fit" or "unfit" for IC. We compared outcomes of older patients with newly diagnosed AML receiving 10-day decitabine with venetoclax (DEC10-VEN) vs IC. DEC10-VEN consisted of daily venetoclax with decitabine 20 mg/m 2 for 10 days for induction and decitabine for 5 days as consolidation. The IC cohort received regimens containing cytarabine ≥1 g/m 2 /d. A validated treatment-related mortality score (TRMS) was used to classify patients at high-risk or low-risk for TRM with IC. Propensity scores were used to match patients to minimize bias. Median age of the DEC10-VEN cohort (n = 85) was 72 years (range 63-89) and 28% patients were at high-risk of TRM with IC. The comparator IC group (n = 85) matched closely in terms of baseline characteristics. DEC10-VEN was associated with significantly higher CR/CRi compared to IC (81% vs 52%, P < .001), and lower rate of relapse (34% vs 56%, P = .01), 30-day mortality (1% vs 24%, P < .01), and longer overall survival (OS; 12.4 vs 4.5 months, HR = 0.48, 95%CI 0.29-0.79, P < .01). In patients at both at high-risk and low-risk of TRM, DEC10-VEN showed significantly higher CR/CRi, lower 30-day mortality, and longer OS compared to IC. Patients at both high-risk and low-risk of TRM had comparable outcomes with DEC10-VEN. In conclusion, DEC10-VEN offers better outcomes compared to intensive chemotherapy in older patients with newly diagnosed AML, particularly in those at high-risk of TRM., (© 2020 Wiley Periodicals LLC.)

Background: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Addition of antithymocyte globulin (ATG) or post-transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings., Methods: We compared the outcomes of adults with acute myeloid leukemia undergoing allo-HSCT from HLA-identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913)., Results: Patients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P < .01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P < .01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P < .01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P < .01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P < .02)., Conclusion: PTCY is feasible in an HLA-identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD., (© 2020 American Cancer Society.)

Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo-SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo-SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two-year leukemia-free survival (LFS), overall survival (OS) and graft-versus-host disease (GVHD)-free, and relapse-free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non-relapse mortality (NRM) and superior OS in comparison to patients with a KPS score <80% (p < 0.001). In the subgroup of patients with a KPS score =80%, a reduced-intensity conditioning (RIC) regimen was associated with an increased risk of relapse (p = 0.002) and lower GRFS (p < 0.001) compared to myeloablative conditioning (MAC). Differently, in patients with a KPS score <80%, a RIC regimen resulted in lower NRM (p < 0.001), whereas relapse incidence did not differ, thus leading to an improved GRFS (p = 0.008) as compared to MAC. A transplant from a matched sibling donor (MSD) was associated with a reduced incidence of grade III-IV acute GVHD (p < 0.01) and NRM (p < 0.01) in comparison to other donor types. In conclusion, allo-SCT appears feasible in AML patients with a jeopardized KPS score. Survival is significantly affected by the conditioning intensity, which should be adjusted according to the severity of KPS impairment., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) generally confers poor prognosis; however, the clinical outcome remains heterogeneous. We sought to further stratify this subentity of AML by performing a retrospective analysis of 179 adult patients with AML-MRC diagnosed at our institution. Based on 2016 World Health Organization diagnostic criteria, 44 (25%) patients had multilineage dysplasia alone (AML-MRC-M), 74 (41%) had history of myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative disease (AML-MRC-H), and 61 (34%) had MDS-related cytogenetics (AML-MRC-C). AML-MRC-M and hematopoietic stem cell transplantation (HSCT) were associated with prolonged event-free survival (EFS) (P = 0.0051 and P < 0.0001, respectively) and overall survival (OS) (P = 0.0015 and P < 0.0001, respectively), whereas AML-MRC-C and age ≥60 years were associated with shorter EFS (P = 0.028 and P = 0.015, respectively) and OS (P = 0.021 and P = 0.013, respectively). Of note, NPM1 mut did not affect the patient's outcome. Multivariable analysis confirmed HSCT and AML-MRC-C as independent predictors for EFS (P < 0.0001 and P = 0.0342, respectively) and OS (P < 0.0001 and P = 0.0295, respectively). AML-MRC-M was an independent predictor for OS (P = 0.0449). When compared with a control group of 105 patients with normal karyotype AML not otherwise specified (NK-AML-NOS), patients with AML-MRC-M had similar EFS and OS (P = 0.99 and P = 0.91, respectively). However, AML-MRC-H and AML-MRC-C were associated with shorter EFS and OS (P = 0.0002 and P < 0.0001, respectively) than the same control group. In a subset of patients, next-generation sequencing analysis showed AML-MRC-M was associated with ASXL1 mutation compared with NK-AML (56% vs 6%). In conclusion, AML-MRC-M demonstrates a superior clinical outcome compared with the rest of the AML-MRC group. They have comparable outcomes to NK-AML-NOS, and these data suggest AML-MRC-M may be considered not to be classified in the same group as patients with other AML-MRC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Patients with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML) respond to conventional induction chemotherapy, with remission rates similar to those seen in other subtypes; however, they are much more likely to relapse and relapse is rapid. For this reason, eligible patients receive consolidation therapy with early allogenic transplantation, but the recurrence rate remains high, even after transplantation. Moreover, the optimal therapy for patients with FLT3-ITD AML who relapse after allogeneic hematopoietic stem cell transplantation remains unclear. Here, we report a case in which graft-versus-leukemia (GVL) effects were induced by gilteritinib administration after a second transplant from the same donor, resulting in sustained remission of early FLT3-ITD AML relapse after allogeneic transplantation. Several studies suggest that the benefits of FLT3 tyrosine kinase inhibitors (FLT3-TKI) after allogeneic transplantation are attributable to GVL induction, as well as direct effects on FLT3 mutation-positive leukemia cells. With this in mind, we induced lymphodepletion using L-PAM to further enhance GVL induction by donor lymphocytes and FLT3-TKI. We believe that enhancement of GVL induction by lymphodepletion should be considered before FLT3-TKI use, if the prognosis is very poor, such as in patients with recurrence following allogeneic transplantation.

Introduction: Myeloid sarcoma (MS) is a rare tumor mass. It may occur at any extramedullary anatomic sites but is uncommon in the sinonasal location.MS commonly presents concurrently with acute myeloid leukemia (AML), but it may predate AML over several months or years, named isolated MS., Patient Concerns: We report a case of a 15-month-old child who presented with mouth breathing, bilateral rhinorrhea, palpebral edema and proptosis. The routine blood tests were normal for the first few months. Computed tomography scan revealed neoplasm in nasal cavity., Diagnosis: The patient was definitely diagnosed with isolated MS in the nasal cavity through immunohistochemistry combined with clinical features and radiological investigations, and MS further progressed to AML which was confirmed by hematologist., Interventions: Endoscopic sinus surgery was performed to acquire specimens. After diagnosis, the patient was promptly treated with systemic chemotherapy., Outcomes: All symptoms gradually subsided and the mass of nasal cavity was invisible. No relapse occurred during follow-up., Conclusion: Sinonasal MS may be misdiagnosed and should be considered when symptoms persist and worsen. Prompt clinic examinations are essential for cases with suspected MS. Diagnosis of MS is dependent on the immunohistological investigations combined with clinical features, radiological investigations. Early diagnosis and systemic chemotherapy are vital for patients to achieve best prognosis.

Background: The optimal conditioning regimen for alloHCT in children with myeloid malignancies remains undefined., Procedure: We performed a retrospective review of children undergoing alloHCT for AML and MDS over a 10-year period (2008-2018) at our institution, comparing the outcomes of recipients of either a myeloablative busulfan- or reduced toxicity mel/thio-based conditioning regimen., Results: A total of 49 patients underwent alloHCT for AML/MDS (mel/thio, N = 21; busulfan, N = 28). Mel/thio recipients were selected due to pretransplant comorbidities. Recipients of mel/thio were more likely to have t-AML, and less likely to have MRD <0.1% at the time of alloHCT (57.1% vs 82.1%). Graft failure was more common in busulfan recipients; engraftment kinetics were similar between groups. Sinusoidal obstructive syndrome was diagnosed in 21% of busulfan and no mel/thio recipients (P = .03). One patient in each group died from TRM. Relapse incidence was comparable (mel/thio-29% vs busulfan-32%); however, relapse occurred significantly later in recipients of mel/thio conditioning (median d + 396 vs d + 137; P = .01). As a result, there was a trend toward improved OS at 1 and 3 years in mel/thio recipients (95% vs 74%, P = .06; and 75% vs 50%, P = .11; respectively)., Conclusion: In our single institution, when compared to myeloablative busulfan-based conditioning, use of a mel/thio-based reduced toxicity regimen resulted in comparable outcomes, despite higher risk patient and disease characteristics. Mel/thio recipients had both more comorbidities and higher risk disease profile, which did not translate into higher rates of either TRM or relapse., (© 2020 Wiley Periodicals, Inc.)

With the number of long-term HSCT survivors steadily increasing, attention needs to be focused on the late complications and quality of life. We therefore analyzed the outcome of 101 pediatric patients (<18 years old at the time of HSCT) transplanted for acute leukemia between 1981 and 2015 at Complexo Hospital de Clínicas, Federal University of Paraná, Brazil, and who survived at least two years after HSCT. The median follow-up was 5.9 years (2.0-29.0); median age at follow-up was 17.5 years (2.98-39.0). The 5-year cumulative incidence of relapse was 27.5% (95% CI 18.6%-36.4%). Two-year cumulative incidence of chronic GVHD was 21.8% (95% CI 13.7%-29.8%). Of the 101 patients, 72 patients (71.3%) presented with late effects. Those surviving longer after HSCT experienced more complications. Patients who received TBI-based regimen developed more late effects (P = .013) and more endocrinological complications (P = .024). Endocrinological complications were the most common late sequelae found in this study. For childhood survivors, quality of life was not influenced by age (at HSCT or at last visit), time from HSCT, gender, donor, or GVHD. For survivors that no longer were children, only age at last visit impacted financial domain measures, irrespective of gender, donor, or GVHD. The current study confirms the high burden late complications after pediatric HSCT have on the survivors and underlines the importance of extended follow-up., (© 2020 Wiley Periodicals, Inc.)

Background: The prognosis for relapsed or refractory acute myeloid leukemia (RR-AML) in children is poor, and the preferred salvage chemotherapy is unclear. One regimen is cladribine, cytarabine, and granulocyte-colony stimulating factor (CLAG), but little is known about its efficacy and safety in children with RR-AML., Methods: We enrolled RR-AML patients aged 0-18 years who received modified CLAG regimen for re-induction between July 1, 2015 and April 1, 2018, or conventional induction between August 1, 2011 and April 1, 2018. Patients were followed up to March 31, 2019. Patients underwent allogeneic stem cell transplantation (allo-SCT) or chemotherapy after the induction of complete remission (CR). The CR rate, survival, and side effects were analyzed., Results: The CR rate for induction was 66.7% after one cycle and 75.0% after two cycles of the CLAG regimen in 12 children. The nine children who received conventional chemotherapy had a CR rate of 22.2% after one cycle and 33.3% after two cycles (P = 0.087 vs. CLAG). The 3-year event-free survival (EFS) of the CLAG group and the conventional treatment group were 44.4 ± 15.7% and 22.2 ± 13.8% (P = 0.112). The 3-year overall survival of the two groups were 59.5 ± 16.2% and 22.2% ± 13.8% (P = 0.057). The 3-year EFS for allo-SCT and chemotherapy after CLAG regimen was 66.7 ± 19.2% and 25.0 ± 21.7% (P = 0.015). A single case of chemotherapy-related death was recorded., Conclusion: Our data suggest a promising CR rate using CLAG salvage treatment in childhood RR-AML. Allo-SCT after CR may improve the long-term outcome in these patients.

Purpose of Review: Allogeneic hematopoietic cell transplantation (HCT), with associated graft-versus-leukemia effects, remains the best postremission strategy for patients with intermediate or high-risk acute myeloid leukemia (AML), with a curative potential. Here, we highlight recent advances in allogeneic HCT that broadened access, refined prognostication, and improved outcomes of AML patients undergoing this procedure., Recent Findings: Eligibility for allogeneic HCT continued to expand to AML patients older than 60 years, as well as to patients lacking human leukocyte antigen (HLA)-matched donors with the advent of alternative donor sources, such as umbilical cord blood and HLA-haploidentical transplantation. Molecular profiling of AML has redefined prognostication for patients in specific AML genomic subgroups undergoing allogeneic HCT and has served as a new strategy for measuring minimal residual disease before and after allogeneic HCT. Using high intensity conditioning regimens has emerged as a potential strategy to reduce risk of relapse and improve overall survival, especially in patients with minimal residual disease prior to allogeneic HCT., Summary: As access to allogeneic HCT continues to improve, also, with more refined prognostic strategies, the field continues to move to optimize transplantation approaches by decreasing the risk of relapse and minimizing transplant-related complications.

Background: Identification of biomarkers for acute myeloid leukemia (AML) is important for treating this malignancy. Recent studies have reported that microRNAs (miRNAs) are stably detectable in the blood/plasma and can be used as biomarkers for various types of cancer including AML. The aim of this study was to analyze miR-223 level in serum as a potential indicator for AML diagnosis and prognosis prediction., Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the levels of miR-223 in the serum samples from 131 patients and 70 healthy individuals., Results: The results revealed that serum miR-223 was underexpressed in AML patients, particularly those in intermediate and unfavorable cytogenetic risk groups. Further analysis revealed that serum miR-223 could yield a receiver operating characteristic (ROC) area under the curve (AUC) of 0.849 with 83.2% sensitivity and 81.4% specificity. Moreover, a significant increase in serum miR-223 level was observed in AML subjects after their treatment. Reduced serum miR-223 level was highly associated with aggressive clinical variables and shorter survival of patients. Furthermore, miR-223 expression was identified to be an independent prognostic predictor of worse overall survival., Conclusion: In conclusion, miR-223 may be a reliable diagnostic and prognostic biomarker for AML., (© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Acute myeloid leukemia (AML) is characterized by a malignant transformation and proliferation of myeloid progenitor cells that cause a replacement of normal hematopoiesis. Diagnostic workup for AML includes cytogenetic analysis and mutational screening covering frequently mutated genes in AML. The genetic analysis is required for risk stratification and treatment decisions. Very recently, three novel drugs have been approved for patients who can be intensively treated: a tyrosine kinase inhibitor (midostaurin) for patients with FLT3 mutations, a liposomal formulation of chemotherapy (CPX) for patients with features of secondary AML, and a CD33 antibody-drug conjugate (gemtuzumab-ozogamicin) for AML with CD33 expression. Allogeneic stem cell transplantation remains an important treatment strategy for patients with intermediate- or high-risk AML and for patients with relapsed AML. For elderly patients who cannot undergo intensive treatment, demethylating agents are the treatment of choice. The aim is to prolong life expectancy with acceptable quality of life. In recent clinical trials, novel drugs have shown promising results in this patient population. Some of these drugs have already been approved in the US. Among these drugs are the Bcl‑2 inhibitor venetoclax, which is already approved in Germany for chronic lymphatic leukemia, as well as IDH1/IDH2 inhibitors (the latter for patients with IDH1/IDH2 mutated AML). Acute promyelocytic leukemia represents a special type of AML that should be treated with a combination of all-trans retinoic acid and arsenic trioxide leading to excellent outcome.

Chronic graft-versus-host disease (cGVHD) is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia (n = 280). The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria. A total of 169 patients suffered from cGVHD. The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD (total, 66.0% vs. 53.7%, P = 0.031; moderate to severe, 42.4% vs. 30.1%, P = 0.036) than the patients who had 1 to 2 loci mismatched. The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD (49.2% vs. 32.9%, P = 0.024) compared with the patients who had other donors. The patients who had grades III to IV acute GVHD (aGVHD) had higher 8-year incidence of cGVHD (total, 88.0% vs. 50.4%, P < 0.001; moderate to severe, 68.0% vs. 27.0%, P < 0.001) compared with the patients without aGVHD. In multivariate analysis, grades III to IV aGVHD was the only independent risk factor for cGVHD. Thus, further interventions should be considered in patients with severe aGVHD to prevent cGVHD.

A retrospective review of the medical reports of a patient who was undergoing treatment for graft versus host disease following bone marrow transplant for acute myeloid leukemia was conducted. The patient presented with persistent ocular irritation and injection. For an unclear period of time, he developed proptosis and binocular diplopia with limitation of extraocular motility insidiously. MRI revealed gross enlargement of extraocular muscles and bone marrow aspiration trephine confirmed relapse of leukemia. He then underwent chemotherapy with marked improvement of proptosis and extraocular motility. This case report highlights the importance of the eye care provider's careful assessment of patients with a history of malignancy. The presence of ocular irritation must not distract from the detection of other signs. Proptosis and extraocular motility limitation are rarely associated with graft versus host disease. The presence of these signs warrants orbital imaging to rule out recurrence of the primary malignancy.This case report highlights how proptosis and extraocular motility limitation seen in a patient with graft versus host disease may point to recurrence of the primary malignancy.

Background: The relationship between the expression levels of Wilms' tumor-1 gene (WT1) mRNA in peripheral blood before allogeneic hematopoietic cell transplantation (allo-HCT) and risk of mortality in acute myeloid leukemia (AML) patients in noncomplete remission (non-CR) remains quite elusive., Methods: We retrospectively assessed the impact of the pretransplant WT1 mRNA level on survival after allo-HCT in non-CR AML patients., Results: A total of 125 AML patients, including 46 non-CR patients (36.8%), were analyzed. On multivariate analysis of non-CR AML patients, WT1 mRNA ≥5000 copies/μg RNA was significantly related to increased risk of mortality (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; P = 0.008). Furthermore, in the entire cohort, log10-transformed WT1 mRNA before allo-HCT was found to be significantly associated with the increased risk of mortality irrespective of whether the disease status was CR or non-CR, using Akaike's information criterion. As the pretransplant WT1 mRNA level elevated, the hazard ratio of mortality monotonically increased in a nonlinear manner regardless of remission status, suggesting that WT1 mRNA level in peripheral blood might reflect tumor burden., Conclusions: This study demonstrated that the pretransplant WT1 mRNA level was a powerful prognostic factor in allo-HCT even for non-CR AML patients, and there may be a WT1 mRNA threshold in non-CR patients for benefiting from allo-HCT.

Chronic graft versus host disease (GVHD) is a major complication of the allogeneic stem cell transplant. One of most frequent manifestations of GVHD is the cutaneous compromise with the sclerodermatous variety being the most severe. We considered that the restrictive respiratory compromise and its evolution are not well characterized. We described the functional respiratory alterations of a patient with sclerodermatous chronic GVHD and considered differential diagnosis of pulmonary restriction in this type of patient. We reported the case of a 21-year-old woman with pulmonary restriction secondary to cutaneous sclerosis which was caused by chronic GVHD. This report illustrates the importance of utilizing both functional respiratory tests and diagnosis images to accurately characterize the cause of the respiratory compromise. We believe that the functional alterations described in this case could be caused by the cutaneous disorder found., (Universidad Nacional de Córdoba)

BACKGROUND Data about application of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) on patients with high-risk or intermediate-risk acute myeloid leukemia (AML) in the first complete remission (CR1) are lacking. In this study, we report the outcomes of using unmanipulated haploidentical allogeneic peripheral blood stem cell transplantation (haplo-PBSCT) as post-remission therapy for patients with high-risk or intermediate-risk AML in CR1. MATERIAL AND METHODS From January 2008 to July 2016, 33 patients diagnosed as high-risk or intermediate-risk AML in CR1 undergoing haplo-PBSCT in our institution were enrolled for analysis. The cumulative incidence of platelet and neutrophil recovery, the occurrence of acute graft-versus-host-disease (GVHD) and chronic GVHD, relapse and non-relapse mortality were assessed. Patients' survival rates were estimated using the Kaplan-Meier method. RESULTS The cumulative incidence of grade 2-4 acute GVHD, overall and extensive chronic GVHD was 18.2%, 9.1%, and 6.1%, respectively. 2-year probability of relapse was 9.1%. Disease-free survival and overall survival at 2 years were 72.7% and 75.8%, respectively. CONCLUSIONS Our results showed that unmanipulated haploidentical transplantation with G-CSF primed PBSC alone as a graft source could be an acceptable alternative post-remission treatment for high-risk or intermediate-risk AML patients in CR1 lacking a matched donor.

BACKGROUND Haplo-identical hematopoietic stem cell transplantation (HSCT) has provided potential donors for patients lacking available HLA-matched donors. ABO blood type compatibility has been reported to be associated with HSCT outcomes. However, few studies have investigated the role of ABO compatibility in haplo-identical HSCT of AML patients. MATERIAL AND METHODS We retrospectively analyzed 42 adult acute myeloid leukemia (AML) patients who received unmanipulated haplo-identical peripheral blood HSCT at the Chinese PLA General Hospital between Jan 2013 and Dec 2017. We analyzed the role of ABO compatibility in engraftment, transfusion requirements, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia, acute graft-versus-host disease (GVHD), overall survival (OS), transplantation-related mortality (TRM), relapse, chronic GVHD, and post-transplant lymphoproliferative disorder (PTLD). RESULTS There were no significant differences between the ABO-matched group and the ABO-mismatched group in terms of engraftment, transfusion requirements, CMV and EBV viremia, OS, TRM, relapse, PTLD, and chronic GVHD. Univariate analysis revealed ABO incompatibility is not an independent risk factor of engraftment, transfusion requirements, CMV and EBV viremia, OS, TRM, relapse, PTLD, and chronic GVHD. We found a significantly higher cumulative incidence of aGVHD in the matched group compared with the mismatched group (80.95% vs. 42.86%, p=0.020). In multivariate analysis, ABO mismatch was associated with decreased risk of acute GVHD within 100 days after transplant (hazard ratio 0.492, 95% confidence interval 0.2123-1.14). However, the difference was not statistically significant (p=0.099). CONCLUSIONS This study demonstrated ABO incompatibility is not an independent risk factor of outcomes for AML patients who received unmanipulated haplo-identical peripheral blood HSCT. ABO compatibility might have limited value in haplo-identical donor selection.

BACKGROUND Allogeneic transplantation remains one of the best therapies for high-risk acute myeloid leukemia (HR-AML). MATERIAL AND METHODS This study retrospectively analyzed 126 patients with HR-AML after allogeneic hematopoietic stem cell transplantation (allo-HCST). RESULTS The disease-free survival (DFS) rates of 1 year and 3 years were 58.83% (95%CI: 50.75-68.20%) and 53.09% (95%CI: 44.59-63.22%) respectively. The cumulative relapse rates of 1 year and 3 years were 21.1% (95%CI: 14.4-28.8%) and 25.9% (95%CI: 18.1-34.5%) respectively. The cumulative incidences of III to IV acute graft-versus-host disease (aGVHD) for 100 days was 8.70% (95%CI: 4.6-14.5%). The cumulative rate of extensive chronic graft-versus-host disease (cGVHD) for 1-year was 4.1% (95%CI: 1.5-8.7%). The cumulative transplantation related mortality rate of 1 year and 3 years were 20.1% (95%CI: 13.6-27.6%) and 21.0% (95%CI: 14.3-28.6%) respectively. Univariate analysis revealed that lower overall survival was correlated with age, bacterial or fungal infection, disease status at transplantation, III-IV aGVHD, post-transplantation lymphoproliferative disorders (PTLD), white blood cell engraftment, and extramedullary involvement (P<0.05). The results of multivariate analysis were that the aforementioned factors were also related to lower overall survival except for PTLD (P<0.05). The results of univariate and multivariate analysis were that extramedullary involvement, III-IV aGVHD, and status pre-transplantation influenced DFS (P<0.05). The risk factors for relapse were status pre-transplantation and extramedullary involvement by univariate and multivariate analysis (P<0.05). CONCLUSIONS HR-AML has inferior prognosis. Our study indicated the necessity of achieving remission status prior to hematopoietic stem cell transplantation, and administration of preventive treatments on high-risk patients after hematopoietic stem cell transplantation. In addition, adequate prevention and treatment of complications are needed.

Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for acute myelogenous leukemia (AML); however, a major cause of treatment failure is disease relapse. The purpose of this single-center Phase I study was to determine the safety and tolerability of administration of the CXCR4 inhibitor plerixafor (Mozobil; Sanofi Genzyme) along with myeloablative conditioning in patients with AML undergoing allogeneic HCT. The rationale was that plerixafor may mobilize leukemic stem cells, making them more susceptible to the conditioning chemotherapy (registered at ClinicalTrials.gov; identifier NCT01141543). Three patients were enrolled into each of 4 sequential cohorts (12 patients total). Patients in the first cohort received 1 dose of plerixafor (240 μg/kg s.c.) before the first dose of fludarabine and busulfan, and subsequent cohorts received injections before 2, 3, and 4 days of conditioning chemotherapy. The median age at HCT was 49 years (range, 38 to 58 years). All patients engrafted following HCT, with an absolute neutrophil count ≥.5 × 10 9 /L observed at a median of 14 days (range, 11 to 18 days). Adverse events possibly related to plerixafor were transient and not severe. Main adverse events following the injection were nausea and dizziness in 4 patients (33%) and fatigue in 4 patients (33%). Among the 12 patients, 2 patients (17%) relapsed post-HCT and 6 (50%) were alive at the last follow-up. The median follow-up of survivors was 67 months (range, 53 to 82 months). In conclusion, plerixafor administration is safe and well tolerated when included in a myeloablative conditioning regimen for allogeneic HCT for AML. Further study in a larger cohort is warranted for the investigation of the impact of plerixafor on post-allogeneic HCT outcomes., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Backgroud: Myeloid sarcoma (MS) is a rare neoplasm of immature myeloid precursors that form tumor mass outside the bone marrow. The diagnosis of de novo MS can be challenging, particularly in patients with no prior history of hematologic malignancies or when MS involves unusual anatomic sites., Case Presentation: The patient was a 53-year-old woman with a history of uterine fibroids and vaginal bleeding for many years who presented with a vaginal wall mass. The tumor had histologic and phenotypic features of histiocytic sarcoma, however, overlapping with a possible extramedullary MS. Using a comprehensive genomic profiling, we were able to identify recurrent chromosomal aberrations associated with MS including a rare KMT2A-ELL fusion, losses of chromosomes 1p, 9, 10, 15, 18, and gain of chromosome 1q and mutations in FLT3 and PTPN11, and achived the final diagnosis of a de novo MS. The patient received standard treatment for acute myeloid leukemia regimen with stem cell transplantation and achieved complete remission., Conclusion: Our case illustrates the clinical utility of comprehensive genomic profiling in assisting the diagnosis or differential diagnosis of challenging MS or histiocytic sarcoma cases, and in providing important information in tumor biology for appropriate clinical management.

The inv(3)(q21q26.2) altering a single chromosome 3 homolog is an established myeloid malignancy-associated entity. Comparatively, double inv(3) cases involving both homologs are exceedingly rare with 13 reports across AML, CML and MDS. This scarcity was confirmed by finding only 2 new cases out of 34,898 bone marrows collected during a 55 year period at a large medical center (0.0005%). The double inv(3) was detected by karyotype and confirmed by FISH on both homologs in a 41 year old female and a 72 year old male with AML. In the latter case, a 2.26-fold increase in MECOM RNA level was found using an NGS myeloid gene panel. Chromosomal microarray analysis identified segmental copy-neutral loss-of-heterozygosity (CN-LOH) at 3q21 extending to near the q-arm terminus. This is the third report of distal 3q CN-LOH, substantiating that the double inv(3) arises through somatic repair of acquired segmental LOH. Long term clinical and genetic evaluation revealed no discernible morphologic difference between single and double inv(3) cases, conventional chemotherapy resistance and rapid dominance of the double inv(3) clone. The two new cases are consistent with relatively longer survival of double inv(3) patients in the absence of concurrent chromosome 7 loss compared to those with both abnormalities. Importantly, the first known outcome data of bone marrow transplantation in double inv(3) AML is also presented., (Copyright © 2018. Published by Elsevier Inc.)

Relapse after allogeneic hematopoietic cell transplantation (HCT) for acute leukemia can be reduced when pursued early after first complete remission. The impact of donor age and donor relatedness on the time from diagnosis to transplant in patients with acute leukemia was examined to clarify the design of future prospective studies that can address optimal donor choice. Files of 100 consecutive patients undergoing transplantation for leukemia were reviewed. Recipients of related donors (RDs) and unrelated donors (UDs) were not significantly different in terms of recipient gender, age, underlying diagnosis, disease risk index, graft source, or donor HLA match. UDs were significantly younger than RDs (median age, 29 versus 51, P < .001). Multivariate linear regression revealed that when controlling for age of donor and recipient, the time from diagnosis to transplant was 35% longer with UDs compared with RDs (P = .018). No significant correlation was observed between donor and recipient age on length of time to transplant (P = .134 and P = .850, respectively), when controlling for other variables. The steps in UD procurement that contribute most to the longer time to transplant relate to activating the donor workup and scheduling the donor workup before cell collection. Understanding sources of delay in the transplant process will help transplant centers and UD registries reduce the time to transplant for patients with acute leukemia and will provide necessary insight for the design of prospective controlled studies that can address optimal donor choice., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: To report cases of patients with severe bilateral corneal blindness and recurrent refractory perforation to keratoplasty and conventional treatment, for whom Boston keratoprosthesis (KP) was a satisfactory alternative when combined with a temporalis aponeurosis graft., Description of Cases: The first patient had progressive Lyell syndrome with spontaneous corneal perforation. The second had a severe graft vs. host reaction with a persistent Seidel-positive descemetocele. Despite repeated penetrating keratoplasties, amniotic membrane (AM) transplantations, and buccal mucosal (BM) grafts, they both experienced recurrent corneal perforation. The only solution thus appeared to be Boston Type I KP surgery. One month postoperatively, the first patient had to receive a temporalis aponeurosis (TA) graft, due to thinning of the recipient graft. Six months postoperatively, his visual acuity (VA) was 1/10 without correction, and the corneal status had been stabilized. The second patient underwent KP and TA graft concurrently. Six months after surgery, VA was 2/10 uncorrected, and the local inflammation had been stabilized., Observation: Boston type I keratoprostheses constitute an alternative in cases of severe bilateral corneal blindness with perforation refractory to conventional treatment and surgery, with satisfactory visual results., Discussion: Patients with preoperative severe ocular surface disease are at greater risk of postoperative keratolysis. For our patients with a higher risk, TA graft prevented corneal melt. TA seems to be more effective than AM or BM in preventing corneal thinning or melt., Conclusion: We would recommend performing a TA graft in combination with Boston KP surgery concurrently as first line treatment in eyes with severe ocular surface inflammation., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)