HLA-haploidentical stem cell transplantation in children with inherited bone marrow failure syndromes: A retrospective analysis on behalf of EBMT severe aplastic Anemia and pediatric diseases working parties.

Haploidentical stem cell transplantation (haplo-SCT) represents the main alternative for children with inherited bone marrow failure syndrome (I-BMF) lacking a matched donor. This retrospective study, conducted on behalf of the EBMT SAAWP and PDWP, aims to report the current outcomes of haplo-SCT in I-BMFs, comparing the different in vivo and ex vivo T-cell depletion approaches. One hundred and sixty-two I-BMF patients who underwent haplo-SCT (median age 7.4 years) have been registered. Fanconi Anemia was the most represented diagnosis (70.1%). Based on different T-cell depletion (TCD) approaches, four categories were identified: (1) TCRαß+/CD19+-depletion (43.8%); (2) T-repleted with post-transplant Cyclophosphamide (PTCy, 34.0%); (3) In-vivo T-depletion with ATG/alemtuzumab (14.8%); (4) CD34+ positive selection (7.4%). The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 76% respectively, while that of primary and secondary graft failure was 10% and 8% respectively. The 100-day CI of acute GvHD grade III-IV(95% CI) was 13%, while the 24-month CI of extensive chronic GvHD was 4%. After a median follow-up of 43.4 months, the 2-year overall survival(OS) and GvHD/Rejection-free Survival (GRFS) probabilities are 67% and 53%, respectively. The TCR CD3+αß+/CD19+ depletion group showed a significantly lower incidence of both acute and chronic GvHD and higher OS (79%; p0.013) and GRFS (71%; p < .001), while no significant differences in outcomes have been observed by different diagnosis and conditioning regimens. This large retrospective study supports the safety and feasibility of haplo-SCT in I-BMF patients. TCRαß+/CD19+ depletion offers higher chances of patients' survival, with a significantly lower risk of severe a- and c-GvHD in I-BMFs compared to other platforms.

The Decline of Open, Laparoscopic, and Robotic Splenectomies: A Single Center Experience.

Background: Splenectomy has been performed for various indications from haematological diseases to benign cysts and tumours, and for splenic traumatic injuries. However, there has been a steady decline in splenectomies in the last 20 years. The aim of this study is to establish the reasons behind this decline in splenectomy and to analyse them based on indication, type of splenectomy, and manner of approach (open, laparoscopic or robotic). Material and Methods: This is a retrospective study of a single centre experience of all the splenectomies, both total and partial, performed in the Department of General Surgery of Fundeni Clinical Institute (Bucharest) between 2002 and 2023. Only surgeries for primary splenic diseases were selected, splenic resections as part of other major operations were not included. Results: Between 2002 and 2023, 876 splenectomies were performed in the Department of General Surgery of Fundeni Clinical Institute (Bucharest). Most splenectomies (n=245) were performed for immune thrombocytopenic purpura (ITP), followed by benign tumours and cysts (n=136), lymphoma (n=119), hypersplenism due to cirrhosis (n=107) and microspherocytosis (n=95). Other indications included myelodysplastic syndrome (n=39), trauma (n=35), thalassemia (n=22), leukaemia (n=18) and also there were 60 splenectomies that were performed for hypersplenism of unknown cause. There were 795 total splenectomies (TS) and 81 partial splenectomies (PS). There was a decline in the number of splenectomies both TS and PS for all these indications, most notably in the case of ITP, microspherocytosis and hypersplenism due to cirrhosis with no splenectomies performed for these indications since 2020. Conclusion: With the development of new lines of treatment, advances in interventional radiology and in surgery with the spleen parenchyma sparing options, the need for total splenectomy has been greatly reduced which is reflected in the decline in the number of splenectomies performed in the last 20 years in our clinic.

Design and preclinical testing of an anti-CD41 CAR T cell for the treatment of acute megakaryoblastic leukaemia.

Acute megakaryoblastic leukaemia (AMkL) is a rare subtype of acute myeloid leukaemia (AML) representing 5% of all reported cases, and frequently diagnosed in children with Down syndrome. Patients diagnosed with AMkL have low overall survival and have poor outcome to treatment, thus novel therapies such as CAR T cell therapy could represent an alternative in treating AMkL. We investigated the effect of a new CAR T cell which targets CD41, a specific surface antigen for M7-AMkL, against an in vitro model for AMkL, DAMI Luc2 cell line. The performed flow cytometry evaluation highlighted a percentage of 93.8% CAR T cells eGFP-positive and a limited acute effect on lowering the target cell population. However, the interaction between effector and target (E:T) cells, at a low ratio, lowered the cell membrane integrity, and reduced the M7-AMkL cell population after 24 h of co-culture, while the cytotoxic effect was not significant in groups with higher E:T ratio. Our findings suggest that the anti-CD41 CAR T cells are efficient for a limited time spawn and the cytotoxic effect is visible in all experimental groups with low E:T ratio.

TNF-alpha releasing capacity of the whole blood drops after open total splenectomy, but increases after partial/subtotal or minimally invasive splenectomy.

BACKGROUND: The mechanisms that induce immunodeficiency after splenectomy remain unknown. The aim of this study was to measure the cytokine releasing capacity of the whole blood as an expression of the innate immunity after total (TS) and subtotal/partial splenectomy (S/PS) in order to assess the impact of splenectomy on the individual cytokine reactivity. METHODS: We prospectively collected blood before (D0) and at multiple time points after splenectomy (7 days - D7, 30 days - D30, 90 days - D90, 180 days - D180, and 360 days - D360) and measured the cytokines releasing capacity of IL-6, TNF-alpha and IL-10 from whole blood under LPS stimulation which we normalized to the monocytes number. RESULTS: When analyzing all splenectomies at D0, D7 and D30, normalized ΔTNF-alpha significantly dropped after splenectomy (p = .0038) and normalized ΔIL-6 and ΔIL-10 did not significantly change. More specifically, normalized ΔTNF-alpha dropped after TS (p = .0568) and significantly increased after S/PS (p = .0388). Open surgery induced a decrease in normalized ΔTNF-alpha (p = .0970), whereas minimally invasive (MI) surgery significantly increased the normalized ΔTNF-alpha releasing capacity (p = .0178). The cytokine levels were heterogenous between pathologies at D0, and ΔIL-6 dropped mainly in cirrhotic patients after splenectomy (all underwent TS), ΔTNF-alpha dropped in immune thrombocytopenic purpura patients (all underwent TS), but increased in spherocytosis (91% underwent S/PS) after splenectomy. CONCLUSIONS: Splenectomy induces a decrease of the pro-inflammatory cytokine TNF-alpha and if splenic parenchyma is spared and the surgery is performed MI, this change is hindered.

A Population Pharmacokinetic Modeling and Simulation Study of Posaconazole Oral Suspension in Immunocompromised Pediatric Patients: A Short Communication.

BACKGROUND: Posaconazole oral suspension emerged as a promising candidate for prophylaxis of invasive fungal infections in immunocompromised children. Its pharmacodynamic advantages include a broad-spectrum activity and a favorable safety profile; however, they are overshadowed by its large pharmacokinetic (PK) variability, which might cause subtherapeutic exposure. The aim of this study was to develop a population (pop) PK model based on rich sampling data to better understand the PK of posaconazole oral suspension in pediatric patients. METHODS: Data were obtained from a prospective interventional study involving hospitalized pediatric patients with a hematologic malignancy and prophylactically treated with posaconazole oral suspension. After constructing the popPK model, the probability of target attainment (PTA; 100% T ≥ 0.7 mg/L) for prophylaxis under fixed, body weight-based, and body surface area-based dosing was evaluated using Monte Carlo simulation. RESULTS: Fourteen patients contributed 112 posaconazole plasma concentrations. The PK of posaconazole was adequately described by a 1-compartment model with lag time 2.71 hours [13%]; nonlinear bioavailability ED50 99.1 mg/m2 (fixed); first-order absorption rate constant 0.325 hour-1 [27%]; apparent volume of distribution 1150 L [34%]; and apparent clearance 15.4 L/h [24%] (∼70-kg individual). The bioavailability decreased in the presence of diarrhea and co-treatment with a proton pump inhibitor (PPI). The unexplained interindividual variability in posaconazole PK remained large. The PTA was <85%, irrespective of the simulated dosing strategy. Patients without diarrhea and not administered a PPI had the highest PTA (85% under the fixed 300-mg dosing 4 times per day). CONCLUSIONS: Therapeutic drug monitoring is recommended during prophylactic posaconazole therapy in immunocompromised pediatric patients. Large-scale comparative studies are needed to characterize the PK variability between different posaconazole formulations in this cohort.

Challenges of paediatric palliative care in Romania: a focus groups study.

BACKGROUND: The availability of palliative care facilities for children vary considerably among the European member states. In Romania, a country where health expenditure is among the lowest in Europe, palliative care has been mainly provided by charitable organizations. Despite the high number of children needing palliative care, there is scant literature and research available on paediatric palliative care in Romania. The study explores the viewpoints of various paediatric oncology providers with regard to paediatric palliative care provision in Romania. METHODS: Four mixed focus groups were conducted at four university-affiliated paediatric oncology centres located in three distinct Romanian regions (Bucuresti-llfov, Nord-Est and Nord-Vest). The focus groups were analyzed using thematic coding. RESULTS: For many healthcare professionals, emotional burden inherent to the profession; unhealthy work-life balance and understaffing were among the biggest barriers to the successful integration of pediatric palliative care. The lack of staff was attributed to a shortage of financial resources, and to the persisting cultural stigma surrounding palliative care and oncology. Also political turmoil was identified as an important obstacle to palliative care implementation. CONCLUSION: Significant barriers persist limiting the broader implementation of pediatric palliative care in Romania. In order to render palliative care in pediatric oncology more sustainable, more attention should be paid to the mental health care of healthcare professionals working in this field, to the development of mobile palliative care services and to the emigration of skilled medical staff.

MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members.

BACKGROUND/AIMS: Down syndrome associated disorders are caused by a complex genetic context where trisomy 21 is a central component in relation to other changes involving epigenetic regulators and signaling molecules. This unique genetic context is responsible for the predisposition of people with Down syndrome to acute leukemia. Although, the research in this field has discovered some important pathogenic keys, the exact mechanism of this predisposition is not known. METHODS: In this study we applied functional enrichment analysis to evaluate the interactions between genes localized on chromosome 21, genes already identify as having a key role in acute leukemia of Down syndrome, miRNAs and signaling pathways implicated in cancer and cell development and found that miR-155 has a high impact in genes present on chromosome 21. Forward, we performed next generation sequencing on DNA samples from a cohort of patients diagnosed with acute leukemia of Down syndrome and in vitro functional assay using a CMK-86 cell line, transfected with either mimic or inhibitor of the microRNA-155-5p. RESULTS: Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome, which can be correlated to microRNA-155-5p aberrant activity, may play an important role in cell signaling and thus be linked to acute myeloid leukemia. CONCLUSION: Some genes, already shown to be mutated in AML-DS, are potential targets for miR-155. Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome may play an important role in cell signaling and thus be linked to acute myeloid leukemia.

Long-Term Evaluation of the Outcomes of Subtotal Laparoscopic and Robotic Splenectomy in Hereditary Spherocytosis.

BACKGROUND: Hereditary spherocytosis (HS) is a common inherited disease affecting the erythrocyte membrane. Total splenectomy (TS) is effective in reducing hemolysis and decreasing the need of transfusions, but total removal of the spleen represents a potential risk factor for infectious and non-infectious complications. On the other hand, subtotal splenectomy (STS) could be an alternative therapy for HS. The aim of this study is to establish which surgical approach has the best outcome in HS. METHODS: All patients (n = 63) receiving splenectomy for HS between 2002 and 2016 from one institution were retrospectively reviewed. Hemoglobin and reticulocytes levels during preoperative and postoperative follow-up periods were compared. Additionally, a meta-analysis was performed analyzing data regarding hemoglobin and reticulocytes levels from several available studies. RESULT: At 1-year follow-up, our clinical data showed that mean hemoglobin levels increased after TS from (mean ± SD) 9.77 ± 1.82 to 11.88 ± 2.08 g/dl, while after STS from 8.98 ± 1.66 to 11.87 ± 1.38 g/dl. At 3-year and 5-year follow-up after TS, we observed an increase from 9.77 ± 1.82 to 13.59 ± 2.03 and 13.46 ± 1.64 g/dl, respectively. At 3-year and 5-year follow-up after STS in our cohort, we observed an increase from 8.98 ± 1.66 to 13.21 ± 1.95 and 13.68 ± 1.65 g/dl, respectively. The meta-analysis (for a follow-up period of 1 year) showed that the hemoglobin levels increased with 2.61 g/dl (95% CI 2.15-3.08 g/dl; p < 0.001) after TS, and with 1.67 g/dl (95% CI 1.25-2.10 g/dl; p < 0.001) after STS. CONCLUSION: We conclude that subtotal and minimally invasive splenectomy could be considered as the first line of treatment in severe HS cases, especially in children.

Transient leukemia of Down syndrome.

Childhood leukemia is mostly a "developmental accident" during fetal hematopoiesis and may require multiple prenatal and postnatal "hits". The World Health Organization defines transient leukemia of Down syndrome (DS) as increased peripheral blood blasts in neonates with DS and classifies this type of leukemia as a separate entity. Although it was shown that DS predisposes children to myeloid leukemia, neither the nature of the predisposition nor the associated genetic lesions have been defined. Acute myeloid leukemia of DS is a unique disease characterized by a long pre-leukemic, myelodysplastic phase, unusual chromosomal findings and a high cure rate. In the present manuscript, we present a comprehensive review of the literature about clinical and biological findings of transient leukemia of DS (TL-DS) and link them with the genetic discoveries in the field. We address the manuscript to the pediatric generalist and especially to the next generation of pediatric hematologists.

Haploidentical Donors: Can Faster Transplantation Be Life-Saving for Patients with Advanced Disease?

Haploidentical stem cell transplantation is a therapeutic option for patients without an HLA-matched donor. It is increasingly being used worldwide due to the application of posttransplantation cyclophosphamide and is associated with lower incidence of graft-versus-host disease and treatment-related mortality. Haploidentical donors are generally available for most patients and stem cells can be rapidly obtained. Delays in transplantation while waiting for unrelated donor cells can be potentially problematic for patients with advanced disease at risk for progression; thus, the use of haploidentical donors, especially in this setting, can be life-saving. Here we reviewed the literature on haploidentical stem cell transplantation performed with posttransplantation cyclophosphamide.

Parents' Challenges and Physicians' Tasks in Disclosing Cancer to Children. A Qualitative Interview Study and Reflections on Professional Duties in Pediatric Oncology.

BACKGROUND: Professional guidelines encourage physicians to provide children with as much information regarding their health as deemed developmentally and emotionally appropriate. However, empirical research indicates that in clinical practice, an open discussion with children about cancer is often lacking. This study explores impeding factors to and possible strategies for open communication of cancer diagnosis to children from the perspectives of parents and physicians. PROCEDURE: Semi-structured interviews were conducted with 18 parents of children with cancer and 10 treating oncologists. The patient sample was obtained from three pediatric units in Romania. Interviews were transcribed verbatim and interpreted using thematic analysis. Inductive open-coding procedures identified participants' accounts regarding their experiences with cancer diagnosis and treatment. Final themes were selected by grouping codes that formed a pattern in the data. RESULTS: An interplay of mainly three different factors-information overload and emotional turmoil, lack of knowledge and skills for disclosing the diagnosis, and assumptions about burdening the child when discussing cancer-restricted parent-patient communication and subsequently affected physician-patient exchanges. Oncologists recommended open communication at diagnosis, but left the final decision to the parents. They adapted their communication style with patients to parents' preference. CONCLUSIONS: Although physicians need to respect the wishes of children's legal representatives, they also have a duty to promote patients' best interests. We recommend that physicians employ a proactive stance in ensuring that children with cancer are appropriately informed about their diagnosis. In case of parents' arduous objections to full disclosure, an ethical consultation should be considered.

Extracorporeal Photopheresis in Pediatric and Adult Patients with Graft-Versus-Host Disease.

Background/Objectives: Graft-versus-host disease (GVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) resulting from histocompatibility differences between donor and host cells leading to inflammation, tissue damage, and compromised patient outcome. Extracorporeal photopheresis (ECP) is considered as a second-line treatment administered to patients with GVHD who do not respond to corticosteroid treatment or who experience a relapse after an initial response and are therefore classified as steroid refractory (SR). The aim of this study is to evaluate the clinical response rates in both pediatric and adult patients with acute (a) or chronic (c) GVHD and to assess the effectiveness of ECP using the real-world data from a single center. Methods: We performed a retrospective study on 30 patients, including 11 pediatric and 19 adult patients who were treated with ECP as a second-, third-, or fourth-line therapy for (a) and (c) GVHD, alongside corticosteroids and other immunomodulatory medications. The median time from aGVHD onset to ECP was 11.5 days (range: 3 days-9 months), while for cGVHD, the median time was 90 days (range: 2 days-9 months). Results: The overall response rate (ORR) in the aGVHD patient population was 60% with a median of 9 procedures (range: 2-20). For cGVHD patients, the ORR was 70% after a median of 23.5 ECP procedures (range: 8-43). Most patients had skin involvement, with ECP achieving an ORR of 81.8% in aGVHD and 77.7% in cGVHD cases. Conclusions: ECP is a beneficial therapy for patients with (a) and (c) GVHD who have not responded to corticosteroids and other forms of immunosuppressive therapy. Specifically, ECP demonstrated efficacy in improving skin and oral symptoms and permitted reductions in or the elimination of their corticosteroid usage. The study found that extending the duration of ECP treatment was associated with better outcomes, and no detectable complications were observed over a 38-week period.

Triggers for driving treatment of at-risk patients with invasive fungal disease.

Timing of treatment for invasive fungal disease (IFD) is critical for making appropriate clinical decisions. Historically, many centres have treated at-risk patients prior to disease detection to try to prevent fungal colonization or in response to antibiotic-resistant fever. Many studies have indicated that a diagnostic-driven approach, using radiological tests and biomarkers to guide treatment decisions, may be a more clinically relevant and cost-effective approach. The Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) defined host clinical and mycological criteria for proven, probable and possible classes of IFD, to aid diagnosis. However, some patients at risk of IFD do not meet EORTC/MSG criteria and have been termed Groups B (patients with persistent unexplained febrile neutropenia) and C (patients with non-definitive signs of IFD) in a study by Maertens et al. (Haematologica 2012; 97: 325-7). Consequently, we considered the most appropriate triggers (clinical or radiological signs or biomarkers) for treatment of all patient groups, especially the unclassified B and C groups, based on our clinical experience. For Group C patients, additional diagnostic testing is recommended before a decision to treat, including repeat galactomannan tests, radiological scans and analysis of bronchoalveolar lavage fluid. Triggers for stopping antifungal treatment were considered to include resolution of all clinical signs and symptoms. For Group B patients, it was concluded that better definition of risk factors predisposing patients to fungal infection and the use of more sensitive diagnostic tests are required to aid treatment decisions and improve clinical outcomes.

Hematopoietic Stem Cell Transplantation in Acute Promyelocytic Leukemia in the Era of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO).

Acute promyelocytic leukemia (APL) currently represents one of the malignant hemopathies with the best therapeutic responses, following the introduction of all-trans retinoic acid (ATRA) and subsequently of arsenic trioxide (ATO) treatment. As a result, a large proportion of patients with APL achieve long-term responses after first-line therapy, so performing a hematopoietic stem cell transplant as consolidation of first complete remission (CR) is no longer necessary. Even in the case of relapses, most patients obtain a new remission as a result of therapy with ATO and ATRA, but an effective consolidation treatment is necessary to maintain it. The experience accumulated from studies published in the last two decades shows the effectiveness of hematopoietic stem cell transplantation (HSCT) in improving the outcome of patients who achieve a new CR. Thus, the expert groups recommend transplantation as consolidation therapy in patients with a second CR, with the indication for autologous HSCT in cases with molecular CR and for allogeneic HSCT in patients with the persistence of minimal residual disease (MRD) or with early relapse. However, there is a variety of controversial aspects related to the role of HSCT in APL, ranging from the fact that outcome data are obtained almost exclusively from retrospective studies and historical analyses to questions related to the type of transplantation, the impact of minimal residual disease, conditioning regimens, or the role of other therapeutic options. All these questions justify the need for controlled prospective studies in the following years.

Pitfalls in patenting academic CAR-T cells therapy.

INTRODUCTION: Emerging immunotherapies are pushing the boundaries of cancer treatment, with chimeric antigen receptor (CAR)-T cell therapy being one of the most advanced. Due to the increasingly crowded CAR-T cell field, patenting and protecting the intellectual property of these CAR-T cells implies a good knowledge of the legal landscape. AREAS COVERED: The present manuscript focuses on the challenges regarding the patenting process of CAR-T technology, beginning with a description of the main characteristics of CAR-T cells and their functionalities, continuing with the legal landscape applicable to patenting processes, and concluding by presenting the potential strategies to overcome the impediments that can appear when trying to patent CAR-T cells. It is meant to offer insights for those who are exploring possible patenting options in CAR-T cells territory. PubMed and Patenscope databases were used for patent and literature searching (2013-2023). EXPERT OPINION: There is no one-size-fits-all solution in this matter and the medical evolution of this therapy will certainly bring out even more challenges. Comprehensive knowledge of the intellectual property, exposure to potential litigation, growing competition, and the high price of therapy, are strikingly relevant in the broader landscape. Future endeavors would be to take steps toward the harmonization of the CAR-T patenting procedure.

The Significance of CD20 Intensity Variance in Pediatric Patients with B-Cell Precursor Acute Lymphoblastic Leukemia.

B-cell precursor acute lyphoblastic leukemia (ALL) is a common pediatric malignancy and patients may have significant benefits from monoclonal antibodies therapy with increased survival rates. Positive CD20 expression is identified in about half of these patients and its presence may serve as a prognostic factor in disease evolution. We performed a retrospective study including 114 patients diagnosed with B-ALL and evaluated the expression of CD20 through flow cytometry at diagnosis and on day 15. Additional immunophenotypic analyses as well as cytogenetic and molecular genetic analyses were also performed. We observed an increase in the mean fluorescence intensity (MFI) of CD20 between diagnosis-1.9 (1.2-3.26) and day 15: 6.17 (2.14-27.4), (p < 0.0001). Furthermore, we assessed that both diagnosis and day 15 CD20 MFI had an impact on RFS and OS, respectively, for cut-off values of >8.08 at diagnosis and >28.65 at day 15. In conclusion, CD20 expression appears to be a poor prognostic feature of B-ALL in pediatric patients. In this study, stratification of the outcome by the intensity of CD20 has implications concerning the allocation to rituximab-based chemotherapy and may offer new, potentially useful information for pediatric patients with B-ALL.

Acute Lymphoblastic Leukaemia in the Youngest: Haematopoietic Stem Cell Transplantation and Beyond.

The ALL SCTped 2012 FORUM (For Omitting Radiation Under Majority age) trial compared outcomes for children ≥4 years of age transplanted for acute lymphoblastic leukaemia (ALL) who were randomised to myeloablation with a total body irradiation (TBI)-based or chemotherapy-based conditioning regimen. The TBI-based preparation was associated with a lower rate of relapse compared with chemoconditioning. Nevertheless, the age considered suitable for TBI was progressively raised over time to spare the most fragile youngest patients from irradiation-related complications. The best approach to use for children <4 years of age remains unclear. Children diagnosed with ALL in their first year of life, defined as infants, have a remarkably poorer prognosis compared with older children. This is largely explained by the biology of their ALL, with infants often carrying a KMT2A gene rearrangement, as well as by their fragility. In contrast, the clinical presentations and biological features of ALL in children >1 year but <4 years often resemble those presented by older children. In this review, we explore the state of the art regarding haematopoietic stem cell transplantation (HSCT) in children <4 years, the preparative regimens available, and new developments in the field that may influence treatment decisions.

Progress in Hematopoietic Stem Cell Transplantation and Cellular Therapies.

Hematological malignancies are considered to be one of the most important causes of mortality and morbidity in the modern world [...].

Controversial Flow Cytometry Monitoring of a Relapse Case of Pediatric T Cell Acute Lymphoblastic Leukemia: A Case Report.

Acute lymphoblastic leukemia (ALL) is the most frequent childhood cancer, with 80-85% represented by B cell ALL and only 15% by T cell ALL. T Cell ALL (T-ALL) carries a more reserved prognosis compared to B Cell ALL (B-ALL) with regard to response to treatment, risk of relapse, and overall survival. Progress made in current monitoring protocols such as via flow cytometry immunophenotyping (FCM) and by PCR-based amplification of antigen-receptor genes led to improved management of patients with ALL and superior rates of survival. Nevertheless, challenges remain in some clinical cases. This manuscript describes a unique case of T-ALL and raises awareness of such clinical challenges. The article presents an overview of the flow cytometry immunophenotyping at diagnosis and during treatment of a pediatric patient with T-ALL from Fundeni Clinical Institute. In this case, in spite of various therapeutic measures such as first-line chemotherapy for high risk group, salvage chemotherapy (FLAG), conditioning regimen (FLU-BU-TT-ATG), and stem cell transplant, a chemoresistance clone continued to be present.

Outcomes of patients with Down syndrome and acute leukemia: A retrospective observational study.

ABSTRACT: Children with Down syndrome (DS) have a higher risk of developing acute leukemia than do those without DS. There are few studies in the literature about outcome, survival, and difficulties of treating patients with DS and acute leukemia in a developing country. This study aimed to analyze the outcome, response to treatment, survival, treatment complications, and causes of death in patients with DS and acute leukemia compared with those in patients with acute leukemia without DS diagnosed in the same period of time.We conducted a retrospective observational analysis including a cohort of 21 patients with DS and acute leukemia diagnosed between 2009 and 2018 in 3 hemato-oncology centers (2 pediatric centers and 1 adult hematology center). A group of patients with DS-acute lymphoblastic leukemia (DS-ALL) was analyzed and compared with a group of 165 patients with acute lymphoblastic leukemia without DS, and a group of patients with DS-acute myeloid leukemia (DS-AML) was analyzed and compared with a group of 50 patients with acute myeloid leukemia without DS, which was diagnosed during the same period of time (2009-2018) and treated under similar conditions in terms of both treatment protocols and economic resources.The overall survival rates in children with DS-ALL and DS-AML were 35.7% and 57.1%, respectively (P = .438). The overall survival rate was significantly worse in children with DS-ALL than in those with acute lymphoblastic leukemia without DS (35.71% vs 75.80%, P = .001). We noted that treatment-related mortality in the patients with DS-ALL was high (50%) (infections and toxicities related to chemotherapy); this result was significantly different from that for patients with leukemia without DS (P < .0001). The relapse rate was higher in patients with DS-ALL but not significantly higher than that in patients without DS (P = .13).In contrast, the overall survival rate was better for patients with DS-AML than for those with acute myeloid leukemia without DS (57.1% vs 45.1%, P = .47).Because of the particularities of the host, we suggest that DS-ALL and DS-AML should be considered as independent diseases and treated according to specific protocols with therapy optimization per the minimal residual disease.