Genetic Findings of Potential Donor Origin following Hematopoietic Cell Transplantation: Recommendations on Donor Disclosure and Genetic Testing from the World Marrow Donor Association.

Following hematopoietic cell transplantation (HCT), recipients are subjected to extensive genetic testing to monitor the efficacy of the transplantation and identify relapsing malignant disease. This testing is increasingly including the use of large gene panels, which may lead to incidental identification of genetic and molecular information of potential donor origin. Deciphering whether variants are of donor origin, and if so, whether there are clinical implications for the donor can prove challenging. In response to queries from donor registries and transplant centers regarding best practices in managing donors when genetic mutations of potential donor origin are identified, the Medical Working Group of the World Marrow Donor Association established an expert group to review available evidence and develop a framework to aid decision making. These guidelines aim to provide recommendations on predonation consenting, postdonation testing of recipients, and informing and managing donors when findings of potential donor origin are identified in recipients post-transplantation. It is recognized that registries will have different access to resources and financing structures, and thus whenever possible, we have made suggestions on how recommendations can be adapted.

COVID-19 in hematological malignancies: Case series and literature review.

Earlier reports suggest that cancer patients were twice more likely to contract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this report, we describe two patients with hematological malignancies seen at the peak of the first wave of the coronavirus disease 2019 pandemic. A 61-year-old man was referred to our urology unit he was diagnosed with nodular hyperplasia and multiple myeloma and commenced on bortezomib, thalidomide, and dexamethasone combination chemotherapy. He developed a cough and fever, with SPO2 86%, He was positive for SARS-CoV-2 and died a few days later. A 42-year-old man with Hodgkin lymphoma on treatment with Adriamycin, bleomycin, vincristine, and dacarbazine with positive SARS-CoV-2 exposure was diagnosed with pleural effusion at A/E. Three days postadmission, his condition worsened with low SPO2 despite intranasal oxygen. He died after testing positive for SARS-CoV-2. Patients with hematological malignancies tend to have a greater risk of SARS-COV-2 infection and severe disease due to immunosuppression from cancer and its treatment.

Résumé Des rapports antérieurs suggèrent que les patients atteints de cancer étaient deux fois plus susceptibles de contracter le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) infection. Dans ce rapport, nous décrivons deux patients atteints d'hémopathies malignes vus au plus fort de la première vague de la maladie à coronavirus pandémie de 2019. Un homme de 61 ans a été référé à notre unité d'urologie. On lui a diagnostiqué une hyperplasie nodulaire et un myélome multiple. commencé une chimiothérapie combinée bortézomib, thalidomide et dexaméthasone. Il a développé une toux et de la fièvre, avec SPO2 86%, Il était positif pour le SRAS-CoV-2 et est décédé quelques jours plus tard. Un homme de 42 ans atteint d'un lymphome hodgkinien sous traitement par adriamycine, bléomycine, la vincristine et la dacarbazine avec une exposition positive au SRAS-CoV-2 ont reçu un diagnostic d'épanchement pleural à l'A/E. Trois jours après l'admission, son l'état s'est aggravé avec une faible SPO2 malgré l'oxygène intranasal. Il est décédé après avoir été testé positif au SRAS-CoV-2. Les patients atteints d'hématologie les tumeurs malignes ont tendance à avoir un risque plus élevé d'infection par le SRAS-COV-2 et de maladie grave en raison de l'immunosuppression du cancer et de son traitement. Mots-clés: Traitement du cancer, tumeurs malignes hématologiques, immunosuppression, syndrome respiratoire aigu sévère coronavirus 2.

Multiple drug combinations of bortezomib, lenalidomide, and thalidomide for first-line treatment in adults with transplant-ineligible multiple myeloma: a network meta-analysis.

BACKGROUND: Multiple myeloma is a bone marrow-based hematological malignancy accounting for approximately two per cent of cancers. First-line treatment for transplant-ineligible individuals consists of multiple drug combinations of bortezomib (V), lenalidomide (R), or thalidomide (T). However, access to these medicines is restricted in many countries worldwide. OBJECTIVES: To assess and compare the effectiveness and safety of multiple drug combinations of V, R, and T for adults with newly diagnosed transplant-ineligible multiple myeloma and to inform an application for the inclusion of these medicines into the World Health Organization's (WHO) list of essential medicines. SEARCH METHODS: We searched CENTRAL and MEDLINE, conference proceedings and study registries on 14 February 2019 for randomised controlled trials (RCTs) comparing multiple drug combinations of V, R and T for adults with newly diagnosed transplant-ineligible multiple myeloma. SELECTION CRITERIA: We included RCTs comparing combination therapies of V, R, and T, plus melphalan and prednisone (MP) or dexamethasone (D) for first-line treatment of adults with transplant-ineligible multiple myeloma. We excluded trials including adults with relapsed or refractory disease, trials comparing drug therapies to other types of therapy and trials including second-generation novel agents. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias of included trials. As effect measures we used hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) for adverse events. An HR or RR < 1 indicates an advantage for the intervention compared to the main comparator MP. Where available, we extracted quality of life (QoL) data (scores of standardised questionnaires). Results quoted are from network meta-analysis (NMA) unless stated. MAIN RESULTS: We included 25 studies (148 references) comprising 11,403 participants and 21 treatment regimens. Treatments were differentiated between restricted treatment duration (treatment with a pre-specified amount of cycles) and continuous therapy (treatment administered until disease progression, the person becomes intolerant to the drug, or treatment given for a prolonged period). Continuous therapies are indicated with a "c". Risk of bias was generally high across studies due to the open-label study design. Overall survival (OS) Evidence suggests that treatment with RD (HR 0.63 (95% confidence interval (CI) 0.40 to 0.99), median OS 55.2 months (35.2 to 87.0)); TMP (HR 0.75 (95% CI 0.58 to 0.97), median OS: 46.4 months (35.9 to 60.0)); and VRDc (HR 0.49 (95% CI 0.26 to 0.92), median OS 71.0 months (37.8 to 133.8)) probably increases survival compared to median reported OS of 34.8 months with MP (moderate certainty). Treatment with VMP may result in a large increase in OS, compared to MP (HR 0.70 (95% CI 0.45 to 1.07), median OS 49.7 months (32.5 to 77.3)), low certainty). Progression-free survival (PFS) Treatment withRD (HR 0.65 (95% CI0.44 to 0.96), median PFS: 24.9 months (16.9 to 36.8)); TMP (HR 0.63 (95% CI 0.50 to 0.78), median PFS:25.7 months (20.8 to 32.4)); VMP (HR 0.56 (95% CI 0.35 to 0.90), median PFS: 28.9 months (18.0 to 46.3)); and VRDc (HR 0.34 (95% CI 0.20 to 0.58), median PFS: 47.6 months (27.9 to 81.0)) may result in a large increase in PFS (low certainty) compared to MP (median reported PFS: 16.2 months). Adverse events The risk of polyneuropathies may be lower with RD compared to treatment with MP (RR 0.57 (95% CI 0.16 to 1.99), risk for RD: 0.5% (0.1 to 1.8), mean reported risk for MP: 0.9% (10 of 1074 patients affected), low certainty). However, the CIs are also compatible with no difference or an increase in neuropathies. Treatment with TMP (RR 4.44 (95% CI1.77 to 11.11), risk: 4.0% (1.6 to 10.0)) and VMP (RR 88.22 (95% CI 5.36 to 1451.11), risk: 79.4% (4.8 to 1306.0)) probably results in a large increase in polyneuropathies compared to MP (moderate certainty). No study reported the amount of participants with grade ≥ 3 polyneuropathies for treatment with VRDc. VMP probably increases the proportion of participants with serious adverse events (SAEs) compared to MP (RR 1.28 (95% CI 1.06 to 1.54), risk for VMP: 46.2% (38.3 to 55.6), mean risk for MP: 36.1% (177 of 490 patients affected), moderate certainty). RD, TMP, and VRDc were not connected to MP in the network and the risk of SAEs could not be compared. Treatment with RD (RR 4.18 (95% CI 2.13 to 8.20), NMA-risk: 38.5% (19.6 to 75.4)); and TMP (RR 4.10 (95% CI 2.40 to 7.01), risk: 37.7% (22.1 to 64.5)) results in a large increase of withdrawals from the trial due to adverse events (high certainty) compared to MP (mean reported risk: 9.2% (77 of 837 patients withdrew)). The risk is probably slightly increased with VMP (RR 1.06 (95% CI 0.63 to 1.81), risk: 9.75% (5.8 to 16.7), moderate certainty), while it is much increased with VRDc (RR 8.92 (95% CI 3.82 to 20.84), risk: 82.1% (35.1 to 191.7), high certainty) compared to MP. Quality of life QoL was reported in four studies for seven different treatment regimens (MP, MPc, RD, RMP, RMPc, TMP, TMPc) and was measured with four different tools. Assessment and reporting differed between studies and could not be meta-analysed. However, all studies reported an improvement of QoL after initiation of anti-myeloma treatment for all assessed treatment regimens. AUTHORS' CONCLUSIONS: Based on our four pre-selected comparisons of interest, continuous treatment with VRD had the largest survival benefit compared with MP, while RD and TMP also probably considerably increase survival. However, treatment combinations of V, R, and T also substantially increase the incidence of AEs, and lead to a higher risk of treatment discontinuation. Their effectiveness and safety profiles may best be analysed in further randomised head-to-head trials. Further trials should focus on consistent reporting of safety outcomes and should use a standardised instrument to evaluate QoL to ensure comparability of treatment-combinations.

Awareness, Knowledge, and Acceptance of Haematopoietic Stem Cell Transplantation for Sickle Cell Anaemia in Nigeria.

Background. Sickle cell anaemia (SCA) is an inherited condition whose clinical manifestations arise from the tendency of haemoglobin to polymerize and deform red blood cells into characteristic sickle shape. Allogeneic bone marrow transplantation offers a cure. The aim of this study was to determine the level of awareness, knowledge, and acceptance of this beneficial procedure in Nigeria. Materials and Methods. This multicentre cross-sectional study was conducted in 7 tertiary hospitals in Nigeria in 2015. Approval was obtained from each institution's research and ethics committee. A pretested structured questionnaire was administered to respondents aged 18 years and above and to the parents or guardians of those below 18 years of age. Results. There were 265 respondents comprising 120 males and 145 females. One hundred and seventy-one (64.5%) respondents were aware of BMT for the treatment of SCA. About 67.8% (116 of 171) of those who were aware believed SCA can be cured with BMT (p = 0.001) and 49.7% (85 of 171) of the respondents accepted BMT (p = 0.001). Conclusion. Awareness of BMT in Nigeria is low when compared with reports from developed countries. The knowledge is poor and acceptance is low. With adequate information, improved education, and psychological support, more Nigerians will embrace BMT.

Pilot study of omega-3 fatty acid supplements in sickle cell disease.

In a previous retrospective study, it was observed that the greater the amounts of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the blood, the lesser the number of complications of sickle cell disease (SCD) and the higher the steady state haemoglobin level. SCD causes ischaemia-reperfusion injury and inflammation; which can be ameliorated by a metabolite of DHA that down-regulates expression of pro-inflammatory genes. The objectives of this prospective pilot study were to evaluate the effects of DHA and EPA supplements in SCD, and test the hypothesis that these effects are mediated partly by reducing inflammation. Oral DHA and EPA supplements were given to 16 SCD patients for 6 months. We then compared pre- and post-supplementation values of number of crisis, steady state Hb, plasma unconjugated bilirubin and three indices of inflammation: plasma interleukin-6, blood neutrophil and platelet counts. There was a significant reduction in the plasma level of unconjugated bilirubin, and the number of sickle cell crisis; but not in the markers of inflammation. The pilot data suggest that DHA and EPA supplements reduce the number of crisis and steady state haemolysis in SCD; but provide no evidence that these effects are mediated by reducing inflammation.

Challenges for allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia in the era of tyrosine kinase inhibitors.

Following the introduction of the tyrosine kinase inhibitor (TKI) imatinib in the treatment of chronic myeloid leukemia (CML) patients, the allogeneic hematopoietic stem cell transplantation (HSCT) scene in CML has changed dramatically. The number of patients receiving HSCT in first chronic phase (CP) has declined rapidly, as allogeneic HSCT in CP is now performed in these patients only in case of failure or intolerance of TKIs. Second, those CML patients who undergo allogeneic HSCT represent a selection of high-risk patients due to more advanced disease with high rates of accelerated or blast phase (being associated with an increased relapse risk), advanced age and relevant co-morbidities. Efforts at meeting these special challenges are being developed: treatment with TKIs aims to improve the pre-transplant remission status before HSCT. Dose-reduced conditioning protocols were introduced to decrease transplant-related mortality in patients with co-morbidities or older age. In the post-transplant period, TKIs may be administered for prophylaxis and for treatment of post-transplant relapse. Still, the outcome of patients in advanced CML phases remains guarded, and requires an improvement in current transplant strategies.

Ophthalmic manifestations of leukemia in a tertiary hospital population of adult nigerian africans.

PURPOSE: To determine the prevalence and pattern of leukemic ophthalmopathy among adults at the University of Nigeria Teaching Hospital (UNTH), Enugu, south-eastern, Nigeria. MATERIALS AND METHODS: This prospective, observational case series surveyed adult leukemia patients presenting at UNTH's departments of Hematology/Immunology and Ophthalmology from July 2003 to August 2008. The demographic profile, clinical data from for each individual in the cohort were statistically collated and analyzed. A P <0.05 was considered as statistically significant. RESULTS: There were 72 participants (45 males and 27 females), aged 32.7 ± 9.8 years (range, 18 years to 72 years). Leukemic ophthalmopathy was present in 77.8% of subjects. The leading ophthalmic manifestations of leukemia were retinal vascular abnormalities in 50.0% of subjects, conjunctival pallor in 27.8% of subjects, sub-conjunctival hemorrhage in 19.4% of subjects, and retinal hemorrhage in 16.7% of subjects. Ocular co-morbidity was present in 47.2% of subjects. Vision loss occurred in 37.5% of subjects, of which 32.1% was leukemia related, and the remaining due to ocular co-morbidity. Leukemic ophthalmopathy was more prevalent in chronic leukemia (P <0.05), frequently affected the ocular posterior segment (P < 0.05), and often resulted from secondary hematologic complications (P <0.05). There was no gender difference in the prevalence of leukemia (P = 0.0822) or leukemic ophthalmopathy (P = 0.6624). CONCLUSION: The prevalence of leukemic ophthalmopathy in Enugu is high. It is often associated with significant ocular co-morbidity and vision loss. These have implications for clinicians involved in leukemia management. Early diagnosis and regular ophthalmic examinations are recommended to optimize treatment outcomes.

Second allogeneic stem cell transplantation in myeloid malignancies.

For patients with myeloid malignancies who relapse after allogeneic stem cell transplantation (allo-SCT), one salvage option is a second SCT. We retrospectively analyzed outcomes of the second allo-SCT in 25 patients who received at least 2 allografts from related/unrelated donors due to relapse of acute myeloid leukemia, myelodysplastic syndrome or myelofibrosis after the first SCT. A minority of the acute myeloid leukemia/myelodysplastic syndrome patients had reached complete hematological remission before the second SCT (6/25, 24%). Reduced conditioning strategies were performed in the majority (n = 23). Complete remission was achieved in all 21 cases with available data after the second SCT, but relapse was seen in 11/25 patients (44%). After a median follow-up of 18 months (range 6-47), 8/25 patients (32%) were still alive, and of those, 6 (24%) were in stable remission. In 9 cases mortality was associated to relapse and in 8 cases to transplant-related causes (treatment-related mortality; 8/25, 32%). In conclusion, a second SCT offers the chance of stable remission for some patients relapsing with a myeloid malignancy after a first allo-SCT, although high treatment-related mortality and relapse rates remain a problem. Efforts should concentrate on an optimization of conditioning strategies, immunosuppression and post-transplant surveillance for this specific situation.

Clinical profile and home management of sickle cell-related pain: the Enugu (Nigeria) experience.

OBJECTIVE: To document the pattern of and ability of sickle cell anemic patients to manage painful crises at home. SUBJECT AND METHODS: Confirmed HbSS patients or caregivers attending the University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria, were interviewed, using a questionnaire, on their last painful episode. RESULTS: The limbs were involved in all ages, but involvement of the joints, ribs, and spine was uncommon in patients under 5 years old. Pain started between 6 pm and 12 midnight in 33.3%. Analgesics with or without massage or hydration was mostly used at home. 29% of subjects required hospitalization. CONCLUSION: Patients need better access to more potent analgesics to reduce the burden on the health system.

Characterisation of extramedullary relapse in patients with chronic myeloid leukemia in advanced disease after allogeneic stem cell transplantation.

Recently, higher extramedullary relapse rates following allogeneic stem cell transplantation (SCT) in myeloid malignancies were reported e.g. because of selection of poor-risk patients. We analysed five consecutive patients with post-transplant extramedullary relapse of chronic myeloid leukemia (CML) out of a total of 24 patients (21%) undergoing allo-SCT. All five patients with extramedullary relapse had clonal evolution and a history of blast phase (BP). In particular, 56% of the patients in BP had extramedullary relapse with no extramedullary relapse in patients with chronic/accelerated phase. Most frequent manifestation sites were the skeletal system, the muscles/subcutaneous tissue and the central nervous system. In one case chloroma was mimicking myositis of the lower limbs. Combined approaches were performed including irradiation (n = 4), chemotherapy (n = 2), IM (n = 2), dasatinib (n = 4), nilotinib (n = 1), a novel aurora-kinase-inhibitor (n = 1), donor lymphocytes (n = 2) or a second allo-SCT (n = 2). Transient response was achieved in one case, stable partial remissions in two cases, whereas two cases were refractory. Research should focus on prospective studies aiming to improve treatment of extramedullary relapse in stem cell recipients with CML with a special focus on the role of second generation tyrosine kinase inhibitors.

Pegfilgrastim compared to lenograstim after allogeneic peripheral blood stem-cell transplantation from unrelated donors.

We compared a single, subcutaneous fixed dose of 6 mg pegfilgrastim on day +5 with daily lenograstim 263 microg from day +5 and continued until neutrophils were >or=0.5 x 10(9)/L after allogeneic peripheral blood stem-cell transplantation (PBSCT) from unrelated donors for various hematological disorders. Neutrophil engraftment was significantly faster (p = 0.006) in the pegfilgrastim than in the lenograstim group. There was also a tendency towards achieving a faster platelet engraftment (p = 0.06) in the pegfilgrastim group (median 16 vs. 19 days). The duration of thrombocytopenia (<20 x 10(9)/L) was shorter in the pegfilgrastim group (p = 0.05). There were no significant differences in the duration of neutropenia (p = 0.14) and febrile neutropenia (p = 0.25). Differences were not observed in the treatment related mortality, disease free and overall survival between both groups. We conclude that Pegfilgrastim ensured rapid neutrophil engraftment after unrelated allogeneic peripheral SCT, which was at least as effective as daily lenograstim.