Clinical pathways are evidence-based tools that have been integrated into many aspects of pediatric hospital medicine and have proven effective at reducing in-hospital complications from a variety of ...diseases. Adaptation of similar tools for specific, high-risk patient populations in pediatric oncology has been slower, in part due to patient complexities and variations in management strategies. There are few published studies of clinical pathways for pediatric oncology patients. Pediatric patients with a new diagnosis of leukemia or lymphoma often present with one or more "oncologic emergencies" that require urgent intervention and deliberate multidisciplinary care to prevent significant consequences. Here, we present two clinical pathways that have recently been developed using a multidisciplinary approach at a single institution, intended for the care of patients who present with hyperleukocytosis or an anterior mediastinal mass. These clinical care pathways have provided a critical framework for the immediate care of these patients who are often admitted to the pediatric intensive care unit for initial management. The goal of the pathways is to facilitate multidisciplinary collaborations, expedite diagnosis, and streamline timely treatment initiation. Standardizing the care of high-risk pediatric oncology patients will ultimately decrease morbidity and mortality associated with these diseases to increase the potential for excellent outcomes.
The prognosis is dismal (2-year overall survival less than 25%) for childhood, adolescent, and young adult (CAYA) with relapsed and/or refractory (R/R) non-Hodgkin lymphoma (NHL). Novel targeted ...therapies are desperately needed for this poor-risk population. CD19, CD20, CD22, CD79a, CD38, CD30, LMP1 and LMP2 are attractive targets for immunotherapy in CAYA patients with R/R NHL. Novel anti-CD20 monoclonal antibodies, anti-CD38 monoclonal antibody, antibody drug conjugates and T and natural killer (NK)-cell bispecific and trispecific engagers are being investigated in the R/R setting and are changing the landscape of NHL therapy. A variety of cellular immunotherapies such as viral activated cytotoxic T-lymphocyte, chimeric antigen receptor (CAR) T-cells, NK and CAR NK-cells have been investigated and provide alternative options for CAYA patients with R/R NHL. Here, we provide an update and clinical practice guidance of utilizing these cellular and humoral immunotherapies in CAYA patients with R/R NHL.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We describe 6 pediatric patients (12 to 18 y) with relapsed or refractory Hodgkin lymphoma treated with consolidative Brentuximab vedotin (Bv) following reinduction chemotherapy and autologous stem ...cell transplantation. The progression-free survival after autologous stem cell transplantation was 12, 18, 22, 24, 30, and 30 months. Most patients tolerated Bv well although 2 patients developed grade 3 neuropathy that prevent them from completing the scheduled 16 doses of Bv. Consolidative Bv in children and adolescents, as currently recommended for adult patients with early relapsed or refractory Hodgkin lymphoma, is feasible but with some significant toxicities.
The scarcity of malignant Hodgkin and Reed-Sternberg cells hampers tissue-based comprehensive genomic profiling of classic Hodgkin lymphoma (cHL). By contrast, liquid biopsies show promise for ...molecular profiling of cHL due to relatively high circulating tumour DNA (ctDNA) levels
. Here we show that the plasma representation of mutations exceeds the bulk tumour representation in most cases, making cHL particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumours, we demonstrate Hodgkin and Reed-Sternberg ctDNA shedding to be shaped by DNASE1L3, whose increased tumour microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R mutations that are dependent on IL-13 signalling and therapeutically targetable with IL-4Rα-blocking antibodies. Finally, using PhasED-seq
, we demonstrate the clinical value of pretreatment and on-treatment ctDNA levels for longitudinally refining cHL risk prediction and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL, as well as capturing molecularly distinct subtypes with diagnostic, prognostic and therapeutic potential.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Summary
Burkitt lymphoma arising in paediatric post‐solid‐organ transplantation‐Burkitt lymphoma (PSOT‐BL) is a clinically aggressive malignancy and a rare form of post‐transplant lymphoproliferative ...disorder (PTLD). We evaluated 35 patients diagnosed with PSOT‐BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0 years (range: 0.1–14) and age at PSOT‐BL diagnosis was 8.0 years (range: 1–17). All but one patient had late onset of PSOT‐BL (≥2 years post‐transplant), with a median interval from transplant to PSOT‐BL diagnosis of 4.0 years (range: 0.4–12). Heart (n = 18 51.4%) and liver (n = 13 37.1%) were the most frequently transplanted organs. No patients had loss of graft or treatment‐related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma‐specific French–American–British/Lymphomes Malins B (FAB/LMB), n = 13 (37.1%), and a low‐intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n = 12 (34.3%). Median follow‐up was 6.7 years (range: 0.5–17). Three‐year event‐free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT‐BL patients receiving BL‐specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi‐institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT‐BL.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Pediatric Epstein‐Barr virus–negative monomorphic post solid organ transplant lymphoproliferative disorder EBV(−)M‐PTLD comprises approximately 10% of M‐PTLD. No large multi‐institutional ...pediatric‐specific reports on treatment and outcome are available.
Methods
A multi‐institutional retrospective review of solid organ recipients diagnosed with EBV(−)M‐PTLD aged ≤21 years between 2001 and 2020 in 12 centers in the United States and United Kingdom was performed, including demographics, staging, treatment, and outcomes data.
Results
Thirty‐six patients were identified with EBV(−)M‐PTLD. Twenty‐three (63.9%) were male. Median age (range) at transplantation, diagnosis of EBV(−)M‐PTLD, and interval from transplant to PTLD were 2.2 years (0.1–17), 14 years (3.0–20), and 8.5 years (0.6–18.3), respectively. Kidney (n = 17 47.2%) and heart (n = 13 36.1%) were the most commonly transplanted organs. Most were Murphy stage III (n = 25 69.4%). Lactate dehydrogenase was elevated in 22/34 (64.7%) and ≥2 times upper limit of normal in 11/34 (32.4%). Pathological diagnoses included diffuse large B‐cell lymphoma (n = 31 86.1%) and B–non‐Hodgkin lymphoma (B‐NHL) not otherwise specified (NOS) (n = 5 13.9%). Of nine different regimens used, the most common were: pediatric mature B–NHL‐specific regimen (n = 13 36.1%) and low‐dose cyclophosphamide, prednisone, and rituximab (n = 9 25%). Median follow‐up from diagnosis was 3.0 years (0.3–11.0 years). Three‐year event‐free survival (EFS) and overall survival (OS) were 64.8% and 79.9%, respectively. Of the seven deaths, six were from progressive disease.
Conclusions
EFS and OS were comparable to pediatric EBV(+) PTLD, but inferior to mature B‐NHL in immunocompetent pediatric patients. The wide range of therapeutic regimens used directs our work toward developing an active multi‐institutional registry to design prospective studies.
Plain Language Summary
Pediatric Epstein‐Barr virus–negative monomorphic post solid organ transplant lymphoproliferative disorders (EBV(−)M‐PTLD) have comparable outcomes to EBV(+) PTLD, but are inferior to diffuse large B‐cell lymphoma in immunocompetent pediatric patients.
The variety of treatment regimens used highlights the need to develop a pediatric PTLD registry to prospectively evaluate outcomes.
The impact of treatment regimen on relapse risk could not be assessed because of small numbers.
In the intensive pediatric B–non‐Hodgkin lymphoma chemoimmunotherapy group, 11 of 13 patients remain alive in complete remission after 0.6 to 11 years.
No consensus exists about treatment and outcomes of pediatric Epstein‐Barr virus–negative monomorphic post solid organ transplant lymphoproliferative disorder EBV(−)M‐PTLD. Retrospective evidence suggests that EBV(−)M‐PTLD has comparable outcomes to published results in EBV(+) PTLD, but inferior to diffuse large B‐cell lymphoma in immunocompetent pediatric patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
Optimal management of patients with intermediate‐risk lymphocyte‐predominant Hodgkin lymphoma (LPHL) is unclear due to their small numbers in most clinical trials. Children's Oncology Group ...AHOD0031, a randomized phase III trial of pediatric patients with intermediate‐risk Hodgkin lymphoma (HL), included patients with LPHL. We report the outcomes of these patients and present directions for future therapeutic strategies.
Procedure
Patients received two cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE‐PC) followed by response evaluation. Slow early responders were randomized to two additional ABVE‐PC cycles ± two dexamethasone, etoposide, cisplatin, and cytarabine cycles and all received involved field radiotherapy (IFRT). Rapid early responders (RERs) received two additional ABVE‐PC cycles. RERs with complete response (CR) were randomized to IFRT or no further therapy. RERs without CR received IFRT.
Results
Ninety‐six (5.6%) of 1711 patients on AHOD0031 had LPHL. Patients with LPHL were more likely to achieve RER (93.6% vs. 81.0%; P = 0.002) and CR (74.2% vs. 49.3%; P = 0.000005) following chemotherapy compared with patients with classical HL. Five‐year event‐free survival (EFS) was superior in patients with LPHL (92.2%) versus classical HL (83.5%) (P = 0.04), without difference in overall survival (OS). Among RERs with CR following chemotherapy (n = 33), there was no difference in EFS or OS between those randomized to receive or not receive IFRT.
Conclusion
Children and adolescents with intermediate‐risk LPHL represent ideal candidates for response‐adapted therapy based on their favorable outcomes. The majority of patients treated with the ABVE‐PC backbone achieve RER with CR status and can be treated successfully without IFRT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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