Secondary involvement of gallbladder by acute lymphoblastic leukemia presenting clinically as cholecystitis in a young patient: a case report.

BACKGROUND: Primary lymphoma of the liver, gallbladder, and extrahepatic bile ducts or secondary involvement of these organs by leukemia is exceedingly rare. Patients with primary lymphoma or leukemic involvement of the biliary tract and liver often present with symptoms and signs of biliary tract obstruction or inflammation. CASE PRESENTATION: We present a case of a 24-year-old male with biliary tract symptoms who underwent laparoscopic cholecystectomy. His precholecystectomy complete blood count performed on the same morning showed 72% lymphocytes while peripheral blood smears showed approximately 15% blasts. Surgeon went ahead with the procedure. Imaging done prior to surgery showed thickened gallbladder, while the liver, biliary tract, and pancreas did not show any thickening or mass lesion. However, the liver was enlarged. Grossly, the gallbladder wall did not show any stones or discrete mass involving the wall. Instead, there was subtle thickening of the gallbladder wall due to diffuse infiltration by the leukemic infiltrate. This lymphoid population reacted with PAX-5 and TdT immunohistochemical antibodies in a diffuse manner confirming precursor B-cell origin. This patient was found to have B-lymphoblastic leukemia involving his bone marrow on further clinical and diagnostic workup. Patient responded well to chemotherapy and is currently on maintenance treatment. He is well 1.5 years after his diagnosis. CONCLUSION: This case highlights a unique and rare scenario where a previously undiagnosed and unsuspected hematologic malignancy initially presented with clinical features of a chronic inflammatory condition involving an abdominal organ owing to secondary involvement by the malignant infiltrate.

Successful Retransplantation With Killer Cell Immunoglobulin-like Receptor Ligand-mismatched Cord Blood in Infant Acute Lymphoblastic Leukemia That Relapsed After Transplantation.

The prognosis of children with KMT2A -rearranged ( KMT2A -r) acute lymphoblastic leukemia (ALL) remains dismal. This report describes the successful retransplantation of a patient with infant ALL who relapsed both bone marrow and central nervous system. The patient received HLA-matched cord blood transplantation (CBT) and relapsed 18 months later. After achieving the second remission, the patient received a killer cell immunoglobulin-like receptor ligand-mismatched CBT with a reduced-intensity conditioning regimen and has been in remission for 52 months. Thus, killer cell immunoglobulin-like receptor ligand-mismatched CBT with reduced-intensity conditioning might be a treatment option for patients with KMT2A- r ALL who relapsed after transplantation, even with extramedullary relapse.

Sphenopalatine Ganglion Block for Postdural Puncture Headaches in a Thrombocytopenic Adolescent Young Adult: A Case Report.

The epidural blood patch is the gold-standard therapy to treat postdural puncture headaches from dural puncture when conservative therapies fail. However, an epidural blood patch is contraindicated in patients with coagulopathy and thrombocytopenia (platelet count of 60,000/µL) due to concerns of an epidural hematoma. We present a case of an adolescent with acute lymphocytic leukemia, thrombocytopenia, and persistent postdural puncture headaches. The patient was successfully treated with a sphenopalatine ganglion nerve block at the bedside without any side effects and complications.

HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning with very low-dose antithymocyte globulin for relapsed/refractory acute leukemia in pediatric patients: a single-institution retrospective analysis.

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.

Effects of second transplantation with T-cell-replete haploidentical graft using low-dose anti-thymocyte globulin on long-term overall survival in pediatric patients with relapse of leukemia after first allogeneic transplantation.

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.

First pregnancy and live birth in Turkey following frozen-thawed ovarian tissue transplantation in a patient with acute lymphoblastic leukemia who underwent cord blood transplantation.

PURPOSE: To report the first live birth after frozen-thawed ovarian transplantation in Turkey and the second case for an acute lymphoblastic leukemia (ALL) survivor in the world. METHODS: A 19-year-old patient underwent ovarian tissue cryopreservation (OTC) before cord blood transplantation in 2010. She was diagnosed as ALL with a bone marrow biopsy revealing 90% blast ALL-L2 type, and karyotype analyses indicated reciprocal translocation at t(9;22)(q34;q11). The patient received the Berlin-Frankfurt-Munster (BFM) protocol, and complete remission was achieved before fertility preservation. Serum AMH level was measured as 1.5 ng/ml, and 12 antral follicles were counted on ultrasound. She was informed about fertility preservation options and decided to proceed with OTC, with her signed consent before cord blood transplantation in April 2011. Ovarian tissue transplantation (OTT) was performed in 2017 when the patient was menopausal with serum FSH levels > 100 IU/ml and estradiol < 20 pg/ml and hematologically in molecular remission. Detailed molecular analysis, standard histology, and immunohistochemistry demonstrated that the thawed tissue is free of malignant cells. RESULTS: Six months following OTT, she had spontaneous menstruation with serum FSH 11 IU/ml and estradiol 53 pg/ml. Two consecutive IVF cycles yielded three top-quality embryos. Following three embryo transfer cycles, one fresh and two frozen, a healthy term live birth was achieved. Frozen-thawed-transplanted tissues were extracted during caesarean delivery upon the patient's request after a total period of 25 months in vivo, and histopathological evaluation revealed that the tissue was free of leukemic infiltration. CONCLUSION: The authors report the first pregnancy and live birth in Turkey and the second live birth in the world following transplantation of frozen-thawed ovarian tissue in a leukemia survivor. As the transplanted tissues were removed during caesarean delivery, histological findings prove the functionality and the malignant-free status of the transplanted tissue during the grafted period.

Invasive Rhino-Orbito-Cerebral Mucormycosis in Pediatric Patient with Acute Leukemia.

BACKGROUND: Invasive fungal infections are a life-threatening complication of cancer treatments, especially in hemato-oncological patients. Mucormycosis is the third leading cause of invasive fungal infections after Aspergillus and Candida infections. The first clinical symptoms are usually non-specific, which can lead to a late diagnosis and delayed therapy. PURPOSE: The objective of this report is to summarize data in the literature about mucormycosis and to present a case report of a patient with acute lymphoblastic leukemia, who developed this infection at our center. Risk factors for the development of mucormycosis, clinical symptoms, radiology, laboratory results, and outcome were retrospectively evaluated. CASE: We describe a 6-years-old female patient with acute lymphoblastic leukemia. During the induction phase of therapy, the patient developed febrile neutropenia and did not respond to therapy with a combination of antibiotics and supportive treatment. Pansinusitis and orbitocellulitis developed. Examination of the biological material revealed that the etiological agent was a Rhizopus sp. The patient was treated with a combination of antimycotic drugs, but the infection disseminated to the central nervous system. She underwent radical surgical resection of the affected tissue. At this time, she is still under treatment with antimycotic and oncology agents, but is in remission of the main diagnosis and in good clinical condition. CONCLUSION: Mucormycosis is an invasive fungal infection with high morbidity and mortality. Early diagnosis and initiation of effective therapy using a combination of amphotericin B administration and surgery are necessary to obtain a favorable outcome. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Manejo anestésico para la resección de masa mediastínica anterior (MMA) en paciente pediátrico. Descripción de un caso clínico / Anesthetic management during anterior mediastinal mass resection in a pediatric patient. A case report

Las complicaciones inducidas por anestesia general (AG) y relajación neuromuscular (RNM) en cirugía de masa mediastínica anterior pueden ser graves, sobre todo si existe clínica de compresión de la vía aérea o grandes vasos, como disnea u ortopnean entre otros. Es preferible realizar el procedimiento en ventilación espontánea para evitar el colapso respiratorio o cardiovascular por decúbito supino o por pérdida de la presión negativa intratorácica con la AG y RNM. En caso de precisar decúbito supino y RNM se realizarán paso a paso con técnicas de rescate preparadas (posición de rescate, broncoscopio, esternotomía). Una correcta evaluación preoperatoria, adecuada planificación y abordaje multidisciplinar permiten realizar una anestesia y cirugía seguras. Presentamos el caso de un niño con antecedentes de ortopnea severa con diagnóstico de masa mediastínica anterior, linfoma linfoblástico (parada respiratoria y colapso cardiovascular en sedación para punción lumbar y biopsia de médula ósea) que no responde al tratamiento médico y precisa cirugía de resección bajo AG con RNM

Complications induced by general anesthesia (GA) and neuromuscular relaxation (NMR) in anterior mediastinal mass (AMM) resection can be serious, especially when there are signs of compression of the airway or large vessels (dyspnea, orthopnea, etc.) (1). It is preferable to perform the procedure in spontaneous ventilation to avoid respiratory or cardiovascular collapse due to the supine position or to loss of negative intrathoracic pressure with GA and NMR. If the supine position and NMR are unavoidable, procedures should be performed in a step-wise manner, and rescue strategies should be prepared (rescue position, bronchoscope, sternotomy). Correct preoperative evaluation, adequate planning, and a multidisciplinary approach will ensure patient safety. We present the case of a child with a history of severe orthopnea and a diagnosis of AMM and lymphoblastic lymphoma (respiratory arrest and cardiovascular collapse during sedation for lumbar puncture and bone marrow biopsy) that did not respond to medical treatment and required resection surgery under GA with NMR

Allogeneic peripheral blood stem cell transplantation and accelerated atherosclerosis: An intriguing association needing targeted surveillance. Lessons from a rare case of acute anterior myocardial infarction.

We report the case of a 23-year-old man who developed an acute ST-elevation myocardial infarction secondary to acute thrombotic occlusion of the proximal left anterior descending coronary artery five years after undergoing chemotherapy, radiotherapy, haematopoietic stem cell transplantation for acute lymphoblastic leukaemia and bulky mediastinal mass involving the pleura and pericardium. His medical history also included Graft versus Host Disease developed 13 months after transplantation and acute myocarditis three months before the actual hospital admission. To the best of our knowledge, coronary artery disease as a complication of haematopoietic stem cell transplantation and low-dose mediastinal radiation therapy in young patients has been rarely reported in the medical literature. Clinicians should have a high degree of suspicion of coronary artery disease in patients treated with allogeneic haematopoietic stem cell transplantation, especially in patients previously treated with target mediastinal radiotherapy, as a group at risk of premature and significantly accelerated atherosclerosis, in order to make a timely and correct diagnosis.

[Use of blinatumomab in children acute lymphoblastic leukemia in the Grand Ouest interregion: A chance for all]. / Expérience du blinatumomab dans les leucémies aiguës lymphoblastiques de l'enfant et de l'adolescent dans l'interrégion Grand Ouest : une chance pour tous.

INTRODUCTION: Relapsed/refractory acute lymphoblastic leukemia (ALL) in children has a pejorative prognosis and justifies to be treated by hematopoietic stem cell transplantation (HSCT). A minimal residual disease (MRD) before transplantation is a major part of prognosis. Blinatumomab, a bispecific antibody CD19+/CD3+, allowed to achieve a cytologic and molecular complete remission in adults with refractory B-precursor ALL. This retrospective study analyses results from a pediatric cohort treated by blinatumomab thanks to an interregional structuring consortium. PATIENTS AND METHODS: Patients between 0 and 23 years old, from the 7 centers of the french "Grand Ouest" interregional network, treated by blinatumomab for a relapsed or refractory ALL, from January 2015 to January 2018, were included. The efficiency of blinatumomab was assessed in terms of complete remission, minimal residual disease, overall survival, and tolerability of treatment. RESULTS: Thirteen of 18 patients achieved a complete remission, with negative minimal residual disease for ten of them. Fourteen patients proceeded to stem cell transplantation,. Eight out of 14 patients obtained long term remission after HSCT. As far as tolerance is concerned, no serious adverse event, neurological or psychiatric disorder, was observed. CONCLUSION: Thanks to an interregional network collaboration, all children with high risk ALL coming from the western french interregion could be treated by blinatumomab. Blinatumomab offered good hematological conditions to undergo HSCT with a good tolerability.

A Single-Center Experience With Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia: A Modest Pitch for Non-Total Body Irradiation Conditioning Regimens.

OBJECTIVES: Allogeneic hematopoietic stem cell transplantation has been used for several decades to treat patients with acute lymphoblastic leukemia. Total body irradiation has been promoted as an important component of conditioning regimens for this process; however, recent reports of chemotherapy-based conditioning regimens have shown comparable outcomes. MATERIALS AND METHODS: We report our experience with radiation-free conditioning using busulfan and cyclophosphamide in 127 pediatric patients with acute lymphoblastic leukemia who were treated between 1997 and 2014. The median age was 11 years (range, < 1 to 15 y), 70% of patients were male, 81.1% received transplants from HLA-matched siblings, 83% received peripheral blood stem cells, 41% were in second complete remission at the time of transplant, and 83% had B-lineage immunophenotype. RESULTS: In patients who were in complete remission at the time of transplant, 5-year overall survival, leukemia-free survival, and relapse rates were 62.48% (95% confidence interval, 52.29-71.09%), 49.43% (95% confidence interval, 39.57-58.53%), and 45.64% (95% confidence interval, 35.85-54.88%), respectively. We observed significant differences between outcomes in patients by time of transplant, presence of chronic graft-versus-host disease, and remission status. CONCLUSIONS: Our relapse rates were comparable to those shown in recent studies, although the transplant-related mortality rate was lower. The results of our study showed that a busulfan/cyclophosphamide conditioning regimen has acceptable outcomes without the undesirable adverse effects of total body irradiation, particularly in pediatric patients. Large multicenter studies are needed to assess less toxic conditioning regimens with fewer adverse effects in these patients.

Esophageal Mycobacterium avium-intracellulare infection in a bone marrow transplant patient: Case report and literature review.

Mycobacterium avium-intracellulare complex (MAC) is the most common cause of nontuberculous mycobacterial (NTM) disease in humans. We report a case of esophageal MAC disease in a patient who had allogeneic bone marrow transplant for acute lymphoblastic leukemia. Although pulmonary MAC in immunocompromised host is not uncommon, there are only a few cases of NTM-associated esophageal mass reported. Our report and literature review highlight the importance of considering MAC in the differential diagnosis of dysphagia or odynophagia.

Chimerism Monitoring by Short Tandem Repeat (STR) Markers in Allogeneic Stem Cell Transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell (allo-HSC) transplantation is used in the treatment of malignant hematological diseases. An important tool in monitoring post-transplantation evolution is represented by the percentage of donor's blood cells found in recipient's blood, known as chimersim. This is useful in predicting the graft rejection and the risk of disease relapse. In this study, we present the importance of multiplex STR markers in chimerism monitoring of a 8 year old girl diagnosed with acute lymphoblastic leukemia (ALL). METHODS: In the pre-transplant stage, saliva on buccal swabs and blood samples in EDTA were collected from the donor and recipient and used as reference samples. The DNA extraction from saliva and blood samples was done using the Pure Link Genomic DNA kit (Invitrogen, USA). For the DNA quantification, the Quantifiler Human DNA kit (Applied Biosystems, USA) was used on an ABI 7500 Real-time PCR system (Applied Biosystems, USA). Amplification of the STR markers was performed using the AmpFLSTR NGM SElect kit (Applied Biosystems, USA) on a ProFlex PCR System. The PCR products were separated and detected on an ABI 3500 Genetic Analyzer (Applied Biosytems, USA). RESULTS: One month post-transplantation of HSC, a mixed chimerism (MC) containing 38% of donor's cells was obtained from a bone marrow aspiration sample. On the 45th day, a new transplantation was performed. On the 15th day after 2nd transplantation, a MC with 91% donor's cells was obtained. On the 21st day after the 2nd transplantation, a complete chimerism (CC) with 100% donor's cells was obtained. CONCLUSIONS: Chimerism monitoring is useful in identifying those patients in risk for relapse or graft rejection.

Severe hematuria in a hematopoietic cell transplant recipient caused by Ureaplasma urealyticum not by BK virus or adenovirus infection.

A 17-year-old male with acute lymphoblastic leukemia developed severe hematuria and scrotal swelling after haploidentical hematopoietic cell transplantation (HCT). Urine culture was negative. BK virus and adenovirus were negative. However, Ureaplasma urealyticum was detected. He showed dramatic improvement after doxycycline treatment. This is the first report in the literature of hemorrhagic cystitis caused by U. urealyticum in a HCT recipient. In HCT recipients with hemorrhagic cystitis, U. urealyticum should be considered as a potential cause.

Fungal infections in hematopoietic stem cell transplantation in children at a pediatric children's hospital in Argentina.

Our primary objective was to describe the incidence of proven or probable invasive fungal infections (IFIs), a devastating complication of hematopoietic stem cell transplant (HSCT), in HCST in a middle-income country. Secondary objectives were to describe factors associated with IFIs and outcomes. In this single center retrospective study, pediatric patients who underwent a first allogeneic or autologous HSCT from 1998 to 2016 were included. Of the 251 HSCT recipients: 143 transplants were allogeneic and 108 were autologous. Overall, 23 (9%) experienced an IFI, mostly due to yeasts (83%). IFIs were more common in allogeneic HSCT (18/143, 13%) than in autologous HSCT (5/108, 5%; P = .045). Of the 23 patients with IFIs, 14 (61%) died, but only 1 directly from IFI (pulmonary aspergillosis). Overall survival at 3 years was 0.42 ± 0.11 in patients with IFIs and 0.60 ± 0.37 in those without IFIs (P = .049). In Argentina, IFIs during HSCT are common. Recipients of allogeneic HSCT are at higher risk, and IFI is associated with reduced overall survival. Future work should focus on interventions to reduce and improve IFI outcomes in children undergoing transplants in low- and middle-income countries.

Comparable results of autologous and allogeneic haematopoietic stem cell transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia in first complete molecular remission: An analysis by the Acute Leukemia Working Party of the EBMT.

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs). METHODS: We retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014. RESULTS: In univariate analysis, the incidence of relapse at 2 years was 47% after autoHSCT, 28% after MSD-HSCT and 19% after URD-HSCT (P = 0.0002). Respective rates of non-relapse mortality were 2%, 18%, and 22% (P = 0.001). The probabilities of leukaemia-free survival were 52%, 55% and 60% (P = 0.69), while overall survival rates were 70%, 70% and 69% (P = 0.58), respectively. In multivariate analysis, there was a trend towards increased risk of overall mortality after MSD-HSCT (hazard ratio [HR], 1.5, P = 0.12) and URD-HSCT (HR, 1.6, P = 0.08) when referred to autoHSCT. The use of total body irradiation (TBI)-based regimens was associated with reduced risk of relapse (HR, 0.65, P = 0.02) and overall mortality (HR, 0.67, P = 0.01). CONCLUSION: In the era of TKIs, outcomes of myeloablative autoHSCT and alloHSCT for patients with Ph+ ALL in first molecular remission are comparable. Therefore, autoHSCT appears to be an attractive treatment option potentially allowing for circumvention of alloHSCT sequelae. Irrespective of the type of donor, TBI-based regimens should be considered the preferable type of conditioning for Ph+ ALL.