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18F-FDG PET / CT is used clinically for the detection of extramedullary lesions in patients with relapsed acute leukemia (AL). However, the visual analysis of 18F-FDG diffuse bone marrow uptake in detecting bone marrow involvement (BMI) in routine clinical practice is still challenging. This study aims to improve the diagnostic performance of 18F-FDG PET/CT in detecting BMI for patients with suspected relapsed AL. Methods: Forty-one patients (35 in training group and 6 in independent validation group) with suspected relapsed AL were retrospectively included in this study. All patients underwent both bone marrow biopsy (BMB) and 18F-FDG PET/CT within one week. The BMB results were used as the gold standard or real “truth” for BMI. The bone marrow 18F-FDG uptake was visually diagnosed as positive and negative by three nuclear medicine physicians. The skeletal volumes of interest were manually drawn on PET/CT images. A total of 781 PET and 1045 CT radiomic features were automatically extracted to provide a more comprehensive understanding of the embedded pattern. To select the most important and predictive features, an unsupervised consensus clustering method was first performed to analyze the feature correlations and then used to guide a random forest supervised machine learning model for feature importance analysis. Cross-validation and independent validation were conducted to justify the performance of our model. Results: The training group involved 16 BMB positive and 19 BMB negative patients. Based on the visual analysis of 18F-FDG PET, 3 patients had focal uptake, 8 patients had normal uptake, and 24 patients had diffuse uptake. The sensitivity, specificity, and accuracy of visual analysis for BMI diagnosis were 62.5%, 73.7%, and 68.6%, respectively. With the cross-validation on the training group, the machine learning model correctly predicted 31 patients in BMI. The sensitivity, specificity, and accuracy of the machine learning model in BMI detection were 87.5%, 89.5%, and 88.6%, respectively, significantly higher than the ones in visual analysis (P < 0.05). The evaluation on the independent validation group showed that the machine learning model could achieve 83.3% accuracy. Conclusions: 18F-FDG PET/CT radiomic analysis with machine learning model provided a quantitative, objective and efficient mechanism for identifying BMI in the patients with suspected relapsed AL. It is suggested in particular for the diagnosis of BMI in the patients with 18F-FDG diffuse uptake patterns.

Acute Lymphoblastic Leukemia is a very aggressive malignant disorder of lymphoid cells in adults, with recurrence (30 to 60% of the cases) after the initial treatment. Until this moment, there is no gold standard therapy for the treatment of adult patients with acute relapsed/refractory lymphoblastic leukemia. In this case report, we describe two cases of relapsed leukemia: one of lymphocytic leukemia B and one of trilineage leukemia, which presented a satisfactory response to treatment with Bortezomib associated with Vincristine, Dexamethasone, and Bendamustine.

Patients with haematological malignancy are often profoundly immune suppressed, and more so if they require more than one line of therapy. Infection should always be considered when they become unwell. We discuss the differential diagnoses of a young man with multiply-relapsed Philadelphia chromosome-positive B-cell acute lymphoblastic leukaemia who presented with neurological symptoms and cerebrospinal fluid lymphocytosis. The diagnostic approach needs to be rapid and structured, and may require microbiology and neurology support. Keywords: CSF lymphocytosis, Lymphocytic pleocytosis, Varicella zoster encephalitis, Inotuzumab, Relapsed leukemia

Chimeric antigen receptor (CAR) T cell therapy has been used as a targeted approach in cancer therapy. Relapsed and refractory acute leukemia in pediatrics has been difficult to treat with conventional therapy due to dose-limiting toxicities. With the recent success of CD 19 CAR in pediatric patients with B cell acute lymphoblastic leukemia (ALL), this mode of therapy has become a very attractive option for these patients with high-risk disease. In this review, we will discuss current treatment paradigms of pediatric acute leukemia and potential therapeutic targets for additional high-risk populations, including T cell ALL, AML, and infant ALL.

5-Aza-2"-deoxycytidine combined with either amsacrine or idarubicin has been applied in a treatment protocol for patients with a relapse of acute myeloid or lymphocytic leukemia. Sixty-three patients received 5-Aza-2"-deoxycytidine 125 mg/m2 as a 6 h infusion every 12 h for 6 days in combination with either amsacrine 120 mg/m2 as a 1 h infusion on days 6 and 7 (n=30) or idarubicin 12 mg/m2 as a 15 min infusion on days 5, 6 and 7 (n = 33). Twenty-three patients (36.5%) obtained a complete remission (CR) ; eight of 30 patients treated with amsacrine and 15 of 33 treated with idarubicin. Patients with an interval of more than 1 year between initial diagnosis and start of the protocol achieved CR in 51.4%, compared to 15.4% for patients with an interval of less than 1 year. Patients with normal cytogenetics had a higher CR rate (61%) than those with abnormal cytogenetic findings (15.8%). Digestive tract and hematologic toxicity was prolonged, compared to standard induction schedules. Median disease-free survival was approximately 8 months, with only 20% of patients staying in remission for more than 1 year. 5-Aza-2"-deoxycytidine is a good antileukemic agent with considerable toxicity. Current results merit further investigations in previously untreated leukemia.

Durch diese Arbeit konnte anhand eines homogenen Patientenkollektivs mit gleicher Diagnose und einem vergleichbaren Risikoprofil gezeigt werden, dass Patienten nach allogener Stammzelltransplantation, vor allem diejenigen mit unverwandten Stammzellspendern, mit erheblich mehr Spätfolgen belastet sind als Patienten nach alleiniger Chemotherapie. Bei einem Rücklauf von 77% konnten schließlich Daten von 111 Patienten aus insgesamt 57 Kliniken in Deutschland, Österreich, Schweiz und Dänemark erhoben werden. Die gehäuften Spätfolgen in der Gruppe der stammzelltransplantierten Patienten waren in der Regel assoziiert mit der chronischen graft-versus-host-Erkrankung sowie mit den toxischen Folgen der Ganzkörperbestrahlung. Dies betrifft Parameter des Wachstums und der Geschlechtsentwicklung, der Infektabwehr, der Funktion der Schilddrüse, der Augen, der Lunge, der Haut bzw. Hautanhangsgebilde sowie des Bewegungsapparats. Bei den anderen erfassten Systemen wie Gehör, Gastrointestinaltrakt, Nieren- und Leberfunktion, Herz, neurologischem System und Allgemeinzustand wurden jeweils keine signifikanten Unterschiede zwischen den Therapiemodi festgestellt. Zweitmalignome traten nicht auf. Beim Vergleich der MRD- versus MUD-transplantierten Patienten fanden sich signifikante Unterschiede bei der Geschlechtsentwicklung, bei der Funktion der Schilddrüse sowie bei der Infektabwehr zu Ungunsten der unverwandt transplantierten Patienten. Die Aussagekraft der Arbeit wird beeinträchtigt durch eine eingeschränkte Patientenzahl und durch fehlende Werte bei diversen untersuchten Parametern, vor allem bei Betrachtung der vorhandenen Werte der tatsächlich gematchten Paare. Die fehlenden Werte sind zu erklären durch das retrospektive Design der Studie und durch das Fehlen verbindlicher Nachsorge- Protokolle. Insgesamt bestätigt sich dennoch, dass die allogene Stammzelltransplantation im Vergleich zu mehrfach und intensiv mit Chemotherapie behandelten Patienten mit mehr und zum Teil gravierenden Spätfolgen belastet ist. Die allogene SZT sollte daher nur bei solchen Patienten zum Einsatz kommen, für die sie eine eindeutige Verbesserung des Gesamtüberlebens bringt. Die Studie konnte die Schwierigkeiten einer retrospektiven Erhebung von Spätfolgen belegen, und führt zum Schluss, dass die für die Lebensqualität essentiellen Daten unbedingt prospektiv erhoben werden müssen. Die Vigilanz für Spätfolgen beinhaltet die Möglichkeit, Therapien ggf. zu modifizieren und Spätfolgen, die Lebensqualität verringern, zu minimieren oder zu vermeiden., Children with relapsed leukemia are particularly exposed to accumulated therapy elements. The analysis of the data aimed to evaluate late effects after chemotherapy and allogenic stem cell transplantation in children with relapsed acute lymphoblastic leukemia. Post remission therapy consists of chemo/radiotherapy or stem cell transplantation alone. Stem cell transplantation is so far considered as preferable post-remission treatment in patients with high risk features. For intermediate risk patients, the indication for stem cell transplantation remains unclear with comparable EFS rates in retrospective analysis. In this context, late effects after both strategies are of decisive significance. Our study was conducted as a matched pair analysis. Patients, all treated according to ALL-REZ-BFM trials 83-96, were matched according to sex, age, site of relapse and duration of complete remission. Data of 111 patients, (77%) was analyzed by means of a questionnaire. Chronic graft-versus-host- disease was a major and significant risk factor for suffering from late effects after therapy. In contrast, patients who received chemotherapy were not at risk from this. Radiation modi and dosage also played an important role. We found significantly fewer problems in patients after chemotherapy concerning immunological status, growth and sexual development, less need for substitution of growth hormones and sexual hormones, less thyroid and pulmonary dysfunction, fewer skin lesions and nail damage, less impaired dental status and fewer movement deficits. No significant differences could be detected in neurological deficits, function of the heart and circulation, eyes, audiologic capacity, renal, liver and gastrointestinal function. Also, no second neoplasmas were reported. Whereas late effects occur at significantly higher rates in a variety of compartments and organs after allogenic stem cell transplantation, no significant effect on general status could be found. Comparison of matched family donor and matched unrelated donor therapy modus revealed patients with unrelated donors at a significantly higher risk of developing problems concerning sexual development, recurrent infections and thyroid dysfunction. Unfortunately, the design of the study lead to a reduced number of patients whose data could be evaluated. Therefore, upcoming treatment protocols should include prospective evaluation. Examination of late effects after therapy has proven to be of utmost importance. In this way, there is a chance of modifying therapies and choosing an individual tailored therapy in order to improve the quality of life of patients treated for malignancies even many years after completing treatment.