Summary
The value of adding rituximab to chemotherapy in children with aggressive B‐cell non‐Hodgkin lymphoma (B‐NHL) is still insufficiently studied. We enrolled 231 patients mean age 9 years old ...(range 2–17); male:female ratio 3·4:1 with Burkitt (BL, 179 patients, 76·7%), diffuse large B‐cell (32 patients, 14%), primary mediastinal B‐cell (14 patients, 6%), and other (6 patients, 2·6%) B‐cell lymphomas in a prospective study of immuno‐chemotherapy. Stages were I–II in 32% and III–IV in 68% of the patients. Four doses of 375 mg/m2 rituximab were added to the Berlin‐Frankfurt‐Munster‐NHL‐90‐like chemotherapy, with methotrexate being reduced or omitted in the first 2 induction blocks. The complete remission rate was 100% in limited‐stage and 91·4% in advanced‐stage patients. Five advanced‐stage patients (2·2%) died in induction and 1 patient with stage 2 B‐NHL died in remission; 11 patients in the high‐risk group progressed on therapy (3 non‐BL are alive after salvage) and 5 relapsed. Sixteen patients (9·7%) with advanced stage disease proceeded to transplant. With a median follow‐up of 46 months, 98·5 ± 1% of patients with limited disease and 88·1 ± 2% (88·1% in Risk Group 3; 82·6% in Risk Group 4) in advanced stages are alive. This study confirmed that combined immunochemotherapy for B‐lymphomas is highly effective in children, despite reducing the intensity of the induction blocks.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time ...with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.
•Conditioning regimens recommended by IEWP for HSCT in WAS lead to nearly 90% survival regardless of donor type or stem cell source.•Treosulfan-based conditioning was associated with an increased incidence of graft failure, mixed chimerism, and secondary cellular therapies.
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The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A‐g) B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) treated ...consistently according to the MLL‐Baby protocol, a moderate‐intensity protocol. Of the 139 patients enrolled in the MLL‐Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A‐r), while the remaining 39 infants (28.1%) had KMT2A‐g. KMT2A‐g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)‐positive, and more likely to be CD10‐positive. The 6‐year event‐free survival and overall survival rates for all 39 patients were 0.74 (standard error SE 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulative incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate‐intensity therapy, as used in the MLL‐Baby protocol in infants with KMT2A‐g BCP‐ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)‐MRD response should be subjected to advanced therapies, such as targeted or immunotherapies.
Sequential monitoring of minimal residual disease (MRD) by molecular techniques or multicolor flow cytometry (MFC) has emerged over the past two decades as the primary tool to optimize treatment in ...pediatric B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). The aim of our study was to compare the prognostic power of repeated MFC–MRD measurement with single‐point MRD assessment in children with BCP‐ALL treated with the reduced‐intensity protocol ALL‐MB 2008. Data from consecutive MFC–MRD at day 15 and day 36 (end of induction, EOI) were available for 507 children with Philadelphia‐negative BCP‐ALL. They were stratified into standard risk (SR, n = 265), intermediate risk (ImR, n = 211), and high risk (HR, n = 31) according to the initial clinical characteristics defined in the ALL‐MB 2008 protocol. Quantitative (relative to quantitative thresholds) and kinetic (logarithmic reduction) assessments of MFC–MRD at both time points effectively separated patients into three groups with different risk of recurrence. On the other hand, starting with low (for the SR group) and moderate (for the ImR group) induction therapy, a single MFC–MRD measurement at EOI proved sufficient to unequivocally identify patients in whom this therapy is highly effective and distinguish them from those who cannot be successfully treated with such therapy. Therefore, initiating treatment with low or moderate treatment from the start, together with careful consideration of initial clinical risk factors and just one EOI–MFC–MRD measurement is simple, inexpensive, and entirely sufficient for treatment optimization. Furthermore, for a large proportion of patients, this approach allows better adjustment, in particular also reduction of therapy intensity than sequential MRD measurements.
We describe novel
ex vivo method for elimination of tumor cells from cell suspension, Laser Activated Nanothermolysis and propose this method for purging of bone marrow and blood transplants. K562 ...and human lympholeukemia cells were eliminated in experiments by laser-induced micro-bubbles that emerge inside individual target cells around selectively formed clusters of light-absorbing gold nanoparticles. Pretreatment of tumor cells with specific monoclonal antibodies and Ig-conjugated 30-nm gold particles allowed the formation of clusters of 10–20 on the surface of cell membrane. Electron microscopy found the nanoparticulate clusters inside the cells. Total (100%) elimination of K562 cells targeted with specific antibodies was achieved with single laser pulses with optical fluence of 5
J/cm
2 at the wavelength of 532 nm without damage to the same cells targeted without specific antibodies. Total elimination of human lymphoblasts from suspension of normal stem cells was achieved by a single laser pulse with the optical fluence of 1.7
J/cm
2, while the damage level of normal cells was 16%.
Aim
The aim of the study was to evaluate the incidence and prognostic impact of central nervous system (CNS) involvement in infants with B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), as ...well as its relation with minimal residual disease (MRD) data.
Methods
A total of 139 consecutive infants with BCP‐ALL from the MLL‐Baby trial were studied. Cerebrospinal fluid (CSF) samples were investigated by microscopy of cytospin slides. MRD was evaluated according to the protocol schedule by flow cytometry and PCR for fusion gene transcripts (FGT).
Results
Involvement of the CNS at any level was found in 50 infants (36.0%). The incidence of CNS involvement was higher in patients with KMT2A gene rearrangements (44.0% for KMT2A‐r vs. 15.4% for KMT2A‐g, p = .003). The outcome of CNS‐positive infants was significantly worse than that of CNS‐negative infants, although this prognostic impact was limited to the KMT2A‐r group (event‐free survival 0.21 for CNS‐positive vs. 0.48 for CNS‐negative infants, p = .044). CNS‐positive infants could not be treated successfully by conventional chemotherapy alone, irrespective of the rapidity of MRD response. In contrast, the combination of initial CNS negativity and FGT‐MRD negativity identified a group comprising up to one‐third of infants with KMT2A‐r ALL who can be treated with chemotherapy and achieve very good outcomes (disease‐free survival above 95%), and remaining patients should be allocated to receive other types of treatment.
Conclusion
We can conclude that this combination of initial CNS involvement and MRD data can significantly improve risk‐group allocation in future clinical trials enrolling infants with ALL.
Current system of childhood cancer registration in Belarus Background. The purpose of this article is to describe the current system of childhood cancer registration in Belarus and the main ...principles of organization of Childhood Cancer Sub-registry of Belarus including the retrospective and prospective (formalized and visualized) data collection. Conclusions. The use of visualized data of the initial diagnostic system not only helps to optimize the prospective recording in the cancer registry, but also contributes to the better verification of individual cases that is sometimes required in the retrospective research and in cases of changes in classification of malignant neoplasm.
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