A rare case of bone marrow infiltration by medulloblastoma in a child.

A seven-year-old boy was previously treated for the primarya posterior fossa tumour, medulloblastoma, with extensive central nervous system metastases including leptomeningeal and intrathecal spinal disease; methylation profiling confirmed a Group 4 tumour. At initial presentation a chemotherapy approach was preferred, due to both his young age and extent of disease; this achieved complete radiological and cytological remission prior to consolidation with high-dose chemotherapy and autologous stem cell rescue. He then experienced an asymptomatic localised posterior fossa relapse on surveillance imaging, treated with complete surgical resection, craniospinal irradiation and maintenance chemotherapy. This chemotherapy was interrupted due to poor count recovery following irradiation, and a bone marrow aspirate and trephine were performed which excluded metastatic medulloblastoma or secondary leukaemia. Alternative maintenance with temozolomide was well tolerated. Unfortunately, end-of-treatment MRI imaging of the neuro-axis revealed an asymptomatic new small enhancing intracranial lesion. An early repeat MRI was performed six weeks later which showed minor progression of the intracranial disease and no intrathecal metastases, but new low T1 signal in multiple vertebral bodies with sparing of T3 and T7 vertebrae (arrows; left image) compared with the imaging performed just six weeks previously. Full blood count revealed Hb 97 g/l, WCC 7.7 x109/l, neutrophils 5.4 x109/l and platelets 204 x109/l. In view of the radiological appearances, bone marrow aspirate and trephine were performed from the posterior iliac crest. Aspirate revealed heavy infiltration with clusters of non-haematopoietic cells, characterized by high nuclear:cytoplasmic ratio, open chromatin and agranular, pale basophilic cytoplasm with vacuolation (right upper image). Trephine immunohistochemistry demonstrated positive staining for synaptophysin, CD56, Neu-N (right lower image), retained INI1 and negative CD99 and desmin, confirming medulloblastoma. Spread of medulloblastoma to the bone marrow is a very rare event. In this case, despite an unremarkable full blood count, radiological changes in the spinal column correlated with easily identified disease in aspirate and trephine samples taken from the posterior iliac crest suggesting widespread marrow infiltration were confirmed by bone marrow examination. Early identification of extracranial metastasis afforded the family and clinicians the opportunity to make informed choices regarding ongoing management

Reducing toxicity in the treatment of lymphoma

While prognosis for lymphoma patients has improved significantly in recent years due to modern treatments, diagnostics and imaging techniques, short-term and late effects of treatment continue to have a detrimental impact on their health. This project set out to investigate three different strategies for reducing the toxicity of treatment for lymphoma: i) drug substitution in Hodgkin lymphoma, (ii) a radiotherapy-free approach to treating primary mediastinal large B-cell lymphoma (PMBL), and (iii) chemotherapy-free treatment of post-transplant lymphoproliferative disorder (PTLD). These strategies are commonly used in clinical practice but have not been tested in prospective, randomised clinical trials.Retrospective, observational, multicentre study designs were chosen to evaluate the above approaches to reducing the toxicity of treatment. To assess the impact of chemotherapy on stem cell genomic health, an analysis of mutation burden and mutational signatures was performed in haematopoietic stem and progenitor cells (HSPC) of previously treated Hodgkin lymphoma patients.The key findings were that replacing procarbazine with dacarbazine in Hodgkin lymphoma treatment maintains an excellent 36-month progression-free survival (PFS) of 92.4%. The substitution also confers several toxicity benefits. Additionally, patients treated with dacarbazine-containing regimens had a far lower excess mutation burden in HSPC. This project showed for the first time that procarbazine is linked to the SBS25 mutational signature.R-DA-EPOCH (Rituximab with dose-adjusted Etoposide, Prednisolone, Vincristine, Cyclophosphamide, Doxorubixin) is highly effective treatment for PMBL (3-year PFS 92.8%). However, in this real-world study 31% of patients received consolidative radiotherapy, while in the landmark Phase II trial radiotherapy was omitted(Dunleavy et al., 2013). In PTLD, our data suggest that a risk-stratified approach with first-line Rituximab monotherapy is effective and safe in real-world practice as well as in clinical trials.In conclusion, the real-world data suggest that the strategies I have studied are effective in reducing toxicities of lymphoma treatment. Choice of chemotherapy regimen may also impact on HSPC genomic health.</p

Minimising the Toxicities of First Line Hodgkin Lymphoma Treatment in the Modern Era.

Peer reviewed: TrueStriking advances in the treatment of Hodgkin lymphoma over the last 30 years have culminated in high rates of disease-free survival in younger patients with early and advanced stage disease. In this review we focus on strategies that have evolved over recent years to reduce short and long-term toxicities of treatment. These strategies include the selection of first-line chemotherapy, the stratification of patients based on initial response and subsequent adaptation of treatment, the addition of novel agents (e.g., brentuximab vedotin), the removal of specific drugs (e.g., bleomycin), the use of drug substitution, and the removal of consolidation radiotherapy based on interim and end of treatment PET assessment. While these strategies have successfully reduced toxicity of Hodgkin lymphoma therapy, the cornerstone of treatment continues to be combination chemotherapy and radiotherapy with significant short- and long-term side effects. To further reduce toxicity while maintaining or improving efficacy, we shall need to incorporate novel agents into our first-line treatment algorithms, and several such potentially practice-changing trials are underway

Relapsed mantle cell lymphoma presenting with lactic acidosis and hypoglycemia: A case report

Lactic acidosis and hypoglycemia are rare presentations of malignancy with a poor prognosis. We present the case of a mantle cell lymphoma patient who relapsed with lactic acidosis and hypoglycemia. Although blood glucose, pH, and lactate normalized following chemotherapy and intensive care support, the patient died from ventilator‐associated pneumonia

Relapsed mantle cell lymphoma presenting with lactic acidosis and hypoglycemia: A case report.

Lactic acidosis and hypoglycemia are rare presentations of malignancy with a poor prognosis. We present the case of a mantle cell lymphoma patient who relapsed with lactic acidosis and hypoglycemia. Although blood glucose, pH, and lactate normalized following chemotherapy and intensive care support, the patient died from ventilator-associated pneumonia

Relapsed mantle cell lymphoma presenting with lactic acidosis and hypoglycemia: A case report.

Lactic acidosis and hypoglycemia are rare presentations of malignancy with a poor prognosis. We present the case of a mantle cell lymphoma patient who relapsed with lactic acidosis and hypoglycemia. Although blood glucose, pH, and lactate normalized following chemotherapy and intensive care support, the patient died from ventilator-associated pneumonia

Incidence and outcomes of post-transplant lymphoproliferative disease after 5365 solid-organ transplants over a 20-year period at two UK transplant centres.

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication of solid-organ transplantation (SOT). We present the incidence and outcomes of PTLD in a cohort of 5365 SOT recipients over a 20-year period at two UK transplant centres. With a median follow-up of 7.7 years, 142 of 5365 patients have developed PTLD. Cumulative incidence was 18% at five years after multivisceral transplant and 1%-3% at five years following the other SOT types. Twenty-year cumulative incidence was 2%-3% following liver and heart transplantation and 10% following kidney transplantation. Median overall survival (OS) following SOT was 16 years, which is significantly reduced compared with the age-adjusted UK population. There is relatively high early mortality following diagnosis of PTLD and only patients surviving two years regained a longer-term survival approaching the non-PTLD SOT cohort. Of 90 patients with monomorphic PTLD, diffuse large B-cell lymphoma, 66 were treated with first-line rituximab monotherapy and 24 received first-line rituximab plus chemotherapy. Up-front rituximab monotherapy does not appear to compromise OS, but the number of patients dying from non-lymphoma causes before and after treatment remains high with both treatment approaches. Multivariate analysis of all 90 monomorphic PTLD patients identified an International Prognostic Index (IPI) of 3+ as the strongest pretreatment variable associating with inferior one-year OS

Managing relapsed refractory lymphoma with palliative oral chemotherapy: A multicentre retrospective study.

PEP-C (prednisolone, etoposide, procarbazine and cyclophosphamide) is an orally administered daily chemotherapy regimen used with palliative intent in relapsed refractory lymphoma. To our knowledge, no data on PEP-C have been reported since the original group described the regimen. Here we present a multicentre retrospective cohort reporting our use of PEP-C in 92 patients over an 8-year period. We find that even heavily pretreated lymphoma can respond to PEP-C, particularly low-grade lymphoma (including mantle cell) and lymphoma that was sensitive to the previous line of systemic therapy (chemosensitive). These characteristics may help in the selection of patients likely to derive benefit. The median overall survival of patients with chemosensitive lymphoma treated with PEP-C is 217 days. Within the limitations of a retrospective cohort, we find that PEP-C is well tolerated: the most common toxicity leading to discontinuation is marrow suppression. We suggest that PEP-C should be considered for patients with relapsed refractory lymphoma in two settings: first, where there is no licensed alternative; and second, where the licensed alternative is an intravenous drug and the patient would prefer to choose an oral chemotherapy option