Leukemia belong to 31% of all childhood malignancies. Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric leukemia accounting for 80–85% of all cases. Progress in diagnostics and therapy of leukemia is dependent on international cooperation. The objective of the study was the analysis of non-hematological toxicity during intensive chemotherapy according to two consecutive intercontinental protocols.
Patients and methods
A total number of 210 children diagnosed for ALL who were treated in single center between 2002 and 2018 were divided in two groups defined by therapeutic protocol: ALL IC-BFM 2002 (group 1) and ALL IC-BFM 2009 (group 2). Data were entered prospectively from 2002 into international ALL IC-BFM 2002 and ALL IC-BFM 2009 registry. Non-hematological toxicity was analyzed according to the criteria followed in protocols, compatible with CTCAE criteria.
The most frequent toxicities included hepatic toxicity with transaminitis and hyperbilirubinemia, infections, oral mucositis and gut toxicity with vomiting, and/or diarrhea. Non-hematological toxicity episodes calculated as a ratio per patient were comparably often observed in both the groups; however, the distribution was different. There were more grade III and less grade II toxicities. This was mainly related to significant increase in the rates of infections and transaminitis. However, there was a significant decrease in vomiting and central and peripheral neurotoxicity.
Intensive treatment of ALL is burdened with frequent severe toxic and infectious complications. Further progress in therapy of pediatric ALL is dependent on sophisticated supportive therapy and very well experienced and knowledgeable therapeutic team.
In spite of the introduction of several new drugs in the last 10 years, multiple myeloma (MM) remains incurable. Thus, an adoptive cellular therapy using chimeric antigen receptor T (CART), a strategy to increase the frequency of tumor-directed and functionally active T cells targeting antigens present on the cancer cell, might change the treatment in MM as it did in lymphoma and ALL. There are several targets for CART therapy in MM on different levels of development, which are discussed in the manuscript. B-cell maturation antigen (BCMA) being tested in the studies of phase 1–2 is the most promising, but so far CART has not been approved in the cure of MM and remains an experimental approach. The hematological society is facing a new technology which with its potential ability to cure MM, in spite of its complexity, cost, and toxicity, will definitely and soon change the landscape of myeloma in Europe and world-wide.
No epidemiological data exist so far on invasive mucormycosis (IM) in Polish hematopoietic cell transplantation (HCT) and pediatric hemato-oncology (PHO) centers. The objective of this study was to analyze the incidence, clinical course, therapy, and outcome of IM in pediatric and adult patients undergoing HCT and children with hemato-oncological diseases in Poland. A total number of 12425 at-risk patients were retrospectively analyzed, and the period between 2010 and 2019 was included. Patients were analyzed in three groups: nontransplant children with malignancies, children undergoing HCT, and adults after HCT. Twenty-one patients were diagnosed with IM, including 15 children (10 non-HCT, 5 HCT) and 6 HCT adults. Proven IM was confirmed in 18 patients, probable in 2 patients, and possible in 1 patient. Proven IM was diagnosed in 7.1% of all patients with invasive fungal diseases (IFDs), including 8.1% among PHO patients, 5.4% among pediatric HCT patients, and 7.0% among adult HCT patients. Clinically, pneumonia was diagnosed in 10 (47.6%) patients, involvement of the paranasal sinuses was found in 3 (14.3%) patients, gastrointestinal disease was noted in 2 (9.5%) patients, and disseminated mucormycosis was found in 6 (28.6%) patients. The probability of overall survival in IM patients was 0.50 ± 0.11. Infection-related mortality (IRM) was 10% for pediatric nontransplant IM patients and 82% for transplant IM (pediatric + adult) patients (p = 0.004). Among the transplant patients, all adults died within 120 days. IRM for pediatric HCT patients was 60% (p = 0.038). The only prognostic factor was HCT, which adversely influenced survival in IM patients.
Oral mucositis is regarded by patients as one of the worst and debilitating complications of conditioning and hematopoietic cell transplantation (HCT). Prevention of mucositis is one of the priorities of supportive therapy during and after conditioning.
The primary objective of the study was the analysis of efficacy of keratinocyte growth factor (KGF, palifermin) used in prophylaxis of oral mucositis in patients undergoing allo-HCT. The secondary objectives of the study included the analysis of the influence of palifermin on clinical course of oral mucositis and early transplant outcomes, as well as analysis of the contraindications of palifermin in patients undergoing allo-HCT.
Patients and methods
A total number of 253 allo-HCT performed between 2003 and 2018 in patients aged 0–19 years in a single center were analyzed. Overall, in 161 HCTs, palifermin was administered.
Patients receiving KGF were transplanted earlier in the context of calendar year, and more often received ATG, mainly due to the higher rate of unrelated donor transplants. Allo-HCT patients who were administered palifermin had shorter time of mucositis (median: 9 vs. 13 days, p < 0.001), lower mucositis grade (median: 2° vs. 3°; p < 0.001), shorter period of total parenteral nutrition (median: 19 vs. 22 days; p = 0.018), and lower incidence of episodes of febrile neutropenia (median: 39.1% vs. 83.1%; p < 0.001).
The use of palifermin has decreased duration and severity of oral mucositis in children after allo-HCT. Palifermin is a safe and well-tolerated compound in children undergoing allo-HCT.
Advanced, Monte Carlo (MC) based dose calculation algorithms, determine absorbed dose as dose to medium-in-medium (Dm,m) or dose to water-in-medium (Dw,m). Some earlier studies identified the differences in the absorbed doses related to the calculation mode, especially in the bone density equivalent (BDE) media. Since the calculation algorithms built in the treatment planning systems (TPS) should be dosimetrically verified before their use, we analyzed dose differences between two calculation modes for the Elekta Monaco TPS. We compared them with experimentally determined values, aiming to define a supplement to the existing TPS verification methodology.
Materials and methods
In our study, we used a 6 MV photon beam from a linear accelerator. To evaluate the accuracy of the TPS calculation approaches, measurements with a Farmer type chamber in a semi-anthropomorphic phantom were compared to those obtained by two calculation options. The comparison was made for three parts of the phantom having different densities, with a focus on the BDE part.
Measured and calculated doses were in agreement for water and lung equivalent density materials, regardless of the calculation mode. However, in the BDE part of the phantom, mean dose differences between the calculation options ranged from 5.7 to 8.3%, depending on the method used. In the BDE part of the phantom, neither of the two calculation options were consistent with experimentally determined absorbed doses.
Based on our findings, we proposed a supplement to the current methodology for the verification of commercial MC based TPS by performing additional measurements in BDE material.
High-dose chemotherapy supported by autologous stem cell transplantation (ASCT) continues to be a standard of care for relapsed diffuse large B-cell lymphoma (DLBCL) and may be considered as a frontline consolidation for a proportion of patients with high-risk features.
We evaluated the feasibility and safety of ASCT for high-risk DLBCL who are in first complete remission after standard treatment with chemotherapy ± rituximab.
Material and methods
A retrospective analysis of 58 patients (36 males and 22 females) receiving up-front ASCT between 1996 and 2018 for remission consolidation.
Of the diagnosed, fifty patients were in clinical stage ≥ III. Forty-two (72%) of transplanted patients had age-adjusted IPI ≥ 2. The “B” symptoms were present in 34 patients. The conditioning consisted of cyclophosphamide, carmustine, etoposide (CBV) in 32 patients, carmustine, cytarabine, etoposide, melphalan (BEAM) in 18, and 8 patients received bendamustine, cytarabine, etoposide, melphalan (BeEAM). The transplant-related mortality was 0% at day +30 and +100 after ASCT. Median overall survival (OS) was 4.2 years whereas progression-free survival (PFS) reached 3.0 years. The estimated 5-year OS and PFS were found to be 66% and 64%, respectively. The presence of “B” symptoms remained significance in multivariate analysis (HR 4.17 [95% CI: 1.19–14.5]; p = 0.02). No grade 3 or 4 non-hematological adverse events were observed.
Up-front ASCT was found to be a safe and feasible procedure with long-term remission in approximately 70% of patients.
Neutropenia is uncommon but a very challenging problem in medicine. It remains a well-known risk factor for the development of infection while conversely neutropenia can be caused by infection or its treatment. The issue is discussed in the paper with respect to different patient populations, medical intervention, and life situations.