Anthony Oyekunle

Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up

We examined retrospectively 44 patients with refractory acute leukemia (acute myeloid leukemia (AML)/acute lymphoblastic leukemia=25/19) who underwent allogeneic transplantation at our center between 11/1990 and 04/2004. The median leukemic blasts was 25% and age 28 years (range, 3–56). Twenty-one patients had untreated relapse, 13 failed reinduction, eight in partial remission and two aplastic. Conditioning was myeloablative using cyclophosphamide, busulfan, total-body irradiation and etoposide (Bu/Cy/VP, n=22; TBI/Cy/VP, n=17; others, n=5) followed by marrow or peripheral blood transplant (n=23/21) from unrelated or related donors (n=28/16). All patients had graft-versus-host disease (GVHD) prophylaxis with cyclosporin and methotrexate. One patient experienced late graft failure. Severe acute-GVHD and chronic-GVHD appeared in eight and 14 patients, respectively. Thirteen patients (30%) remain alive after a median of 25.3 months (range, 2.4–134.1); with 31 deaths, mostly from relapse (n=15) and infections (n=12). Overall survival (OS) and progression-free survival (PFS) at 5 years was 28 and 26%, respectively. OS and PFS were significantly better with blasts ⩽20% and time to transplant ⩽1 year while transplant-related mortality was less with the use of TBI. We conclude that patients with refractory leukemia can benefit from allogeneic BMT, especially with ⩽20% marrow blast.

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.

EBV-Associated Malignancies

Epstein-Barr virus (EBV) infection has been implicated in the aetiopathogenic mechanisms of several neoplastic and non-neoplastic disorders. Although the precise mechanisms of the tumourigenic actions of EBV have not yet been fully elucidated, this virus has been strongly linked to subtypes of Hodgkin’s and non-Hodgkin’s lymphomas (especially Burkitt’s lymphoma), HIV/AIDS lymphomas, nasopharyngeal carcinoma and gastric carcinoma, among several others. The fact that persistent infections occur in greater than 95% of adults with an overall relatively low incidence of EBV related tumours compared with the prevalence of infection shows that there are definitely many other factors (genetic and environmental) that contribute to tumour development in EBV positive individuals. In this article, we review some of the currently available knowledge about these relationships in the commonly encountered EBV-associated malignancies. It is hoped that with continued research in the pathogenic mechanisms of EBV, specific roles will be identified that will facilitate the development of specific targeted therapy.

Degrees of Kidney Disease in Nigerian Adults with Sickle-Cell Disease

Objective: To study degrees of chronic kidney disease (CKD) using creatinine clearance in adult Nigerian patients with sickle-cell disease (SCD). Methods: One hundred SCD patients, made up of 79 HbSS (homozygous haemoglobin S) patients and 21 HbSC (heterozygous haemoglobins S and C) patients, were investigated prospectively, along with 50 normal controls. Their sociodemographic data, weight and drug history were documented. Each participant underwent dipstick urinalysis, and creatinine clearance was calculated following a 24-hour urine collection and serum creatinine measurement. They were categorized into stages of CKD based on the creatinine clearance. Results: Of the 79 HbSS patients, 14 (18%), 28 (35%), 33 (42%) and 4 (5%) had stage 1, 2, 3 and 4 CKD, respectively. In the HbSC group, 3 (14%), 9 (43%) and 9 (43%) patients had stage 1, 2 and 3 CKD, respectively. Proteinuria was noted in 16 (20%) HbSS patients but not in any of the HbSC patients. Of the subjects aged ≤24 years (n = 49), 9 (18%), 18 (37%), 21 (43%) and 1 (2%) had stage 1, 2, 3 and 4 CKD, respectively. Of those aged >24 years (n = 51), 8 (16%), 19 (37%), 21 (41%) and 3 (6%) had stage 1, 2, 3 and 4 CKD, respectively. None of the subjects had stage 5 CKD. Conclusion: In this study, the adult subjects with SCD had various degrees of CKD. Adequate follow-up and active intervention are advocated to delay the onset of end-stage nephropathy.

CD34+-selected stem cell boost for delayed or insufficient engraftment after allogeneic stem cell transplantation

BACKGROUND Poor graft function without rejection may occur after stem cell transplantation (SCT). CD34(+) stem cell boost (SCB) can restore marrow function but may induce or exacerbate GvHD. We therefore investigated the feasibility and efficacy of CD34(+)-selected SCB in some patients with poor graft function. We present the results for eight patients (median age 46 years) transplanted initially for myelofibrosis, acute leukemia, myeloma and NHL. Six patients had received HLA-matched and two mismatched grafts (PB, BM; n=5, 3). After a median of 128 days post-transplant, the median leukocyte and platelet counts were, respectively, 2.05/nL and 18/nL. None had achieved platelet counts >50/nL even though donor chimerism was >95% in seven recipients. METHODS Positive selection of CD34(+) stem cells was performed on a CliniMACS device, observing GMP and achieving a median of 98.5% purity. The patients received a median of 1.7 x 10(6)/kg CD34(+) cells and 2.5 x 10(3)/kg CD3(+) T lymphocytes. RESULTS Hemograms at days +30, +60 and +90, respectively, showed steadily increasing median leukocyte (2.55, 3.15 and 4.20/nL) and platelet (29, 39 and 95/nL) counts. After a median follow-up of 144 days, five patients remained alive. No patient had developed acute or chronic GvHD. One patient died of leukemic relapse and two others of systemic mycosis. DISCUSSION These preliminary results point to the possibility of safely improving graft function using CD34(+) positively selected stem cells without necessarily increasing the incidence of GvHD in patients with poor graft function post-SCT. Experience with more patients and longer follow-up should clarify the optimal role for this procedure.

Molecular diagnostics, targeted therapy, and the indication for allogeneic stem cell transplantation in acute lymphoblastic leukemia.

In recent years, the panel of known molecular mutations in acute lymphoblastic leukemia (ALL) has been continuously increased. In Philadelphia-positive ALL, deletions of the IKZF1 gene were identified as prognostically adverse factors. These improved insights in the molecular background and the clinical heterogeneity of distinct cytogenetic subgroups may allow most differentiated therapeutic decisions, for example, with respect to the indication to allogeneic HSCT within genetically defined ALL subtypes. Quantitative real-time PCR allows highly sensitive monitoring of the minimal residual disease (MRD) load, either based on reciprocal gene fusions or immune gene rearrangements. Molecular diagnostics provided the basis for targeted therapy concepts, for example, combining the tyrosine kinase inhibitor imatinib with chemotherapy in patients with Philadelphia-positive ALL. Screening for BCR-ABL1 mutations in Philadelphia-positive ALL allows to identify patients who may benefit from second-generation tyrosine kinase inhibitors or from novel compounds targeting the T315I mutation. Considering the central role of the molecular techniques for the management of patients with ALL, efforts should be made to facilitate and harmonize immunophenotyping, cytogenetics, and molecular mutation screening. Furthermore, the potential of high-throughput sequencing should be evaluated for diagnosis and follow-up of patients with B-lineage ALL.

Avascular necrosis significantly impairs quality of life in sickle cell disease

Introduction: Quality of life (QoL) assessment has become an integral component of the assessment of the holistic care of patients with chronic diseases, including sickle cell disease (SCD). Objective: To evaluate the quality of life in patients with SCD managed in our centre. Patients and Methods: Eighty consecutive patients with confirmed hemoglobin SS or SC were recruited. Age and sex-matched volunteers served as controls. Ethical approval was obtained from the Institutional Review Board and all participants gave informed consent. Information on socio-demographic, quality of life and clinical variables, including the presence of complications were recorded in a modified version of the WHO Quality of Life Brief version (WHOQOL-BREF) questionnaire. Data was analyzed using Microsoft Excel and SPSS 17 computer softwares. Descriptive statistics were used to represent socio-demographic variables while the Student t-test was used to explore relationship between the variables and the quality of life domains. Results: Significantly fewer participants with SCD are married compared to their age- and sex-matched controls (P = 0.01). Similarly, participants with SCD scored significantly lower in the physical and psychological domains as well as in overall QoL and general health domains compared to controls (P = 0.001). Avascular necrosis of the femur significantly affected the overall QoL and general health of participants with SCD, respectively while the means of the QoL assessment domains were not significantly different in participants with SCD with and without complications, except in the general health domain (P < 0.001). Conclusion: Avascular necrosis of the femoral head significantly affects overall QoL in participants with SCD.

AIDS-related lymphomas in Nigeria an emerging phenomenon

Results There were 161 cases comprising NHL, 42 (25.5%); HL, 15 (9.3%), and BL, 104, (64.6%). Seven (4.3%), aged 2-49 (median = 41) years were retroviral positive. Of these, 4 (3 males, 1 female, aged 28-49 (median = 38.5) years) had NHL, 2 (both females) HL, and 1 case, a 2-year-old boy with HIV since birth, had Burkitt’s and an HIVpositive mother. All, except one female with stage 1 HL, presented late (at least clinical stage IIIb). Three patients with NHL and 1 with late-stage HL succumbed to their disease within 1-3 weeks of hospital admission. The remaining 3 patients had been responding satisfactorily to chemotherapy (CHOP for NHL, ABVD for HL, and COM for Burkitt’s lymphoma.)

The utility of the CKD-EPI formula for determination of glomerular filtration rate in Nigerians with sickle cell disease

Background and objective Predictive formulae for the calculation of estimated glomerular filtration rate (eGFR) are increasingly being used in clinical practice for monitoring of renal function. We evaluated the usefulness of the CKD-EPI formula for eGFR in a population of Nigerian patients with sickle cell disease (SCD). Patients and methods One hundred SCD patients were prospectively studied. Relevant information, including age, weight and sex, was obtained from the participants, whereas creatinine clearance was measured following a 24-h urine collection. The Cockcroft-Gault (C-G) and the CKD-EPI formulae were thereafter used to calculate the glomerular filtration rate (GFR) for all participants. SPSS (version 17) and Microsoft Excel 2007 computer software were used for all data collection and analyses. A P-value of less than 0.05 was considered significant. Results The comparison of measured GFR versus eGFR by the C-G and CKD-EPI formulae in homozygous haemoglobin SS (HbSS) patients yielded correlation coefficients (r values) of 0.667 (P < 0.001) and 0.598 (P < 0.001), respectively. Correspondingly, among the heterozygous haemoglobin S + C (HbSC) patients, measured GFR versus eGFR resulted in r values of 0.819 (P < 0.001) and 0.848 (P < 0.001), respectively. Conclusion The CKD-EPI formula is a good measure of eGFR in our population of SCD patients; however, it did not perform significantly better than the C-G formula.

Chronic myeloid leukaemia presenting as priapism: a report of 2 cases and review of literature.

Introduction: Chronic myeloid leukaemia (CML) patients with hyperleukocytosis may demonstrate signs or symptoms of leukostasis including priapism. Methods: We report two patients with CML who presented with priapism. Results/Observations: Both cases reported achieved full detumescence after commencing chemotherapy for CML. These cases illustrate the importance of full haematological investigations in patients presenting with priapism in accident and emergency as well as urological emergency clinics. Key Words: CML, Hyperleukocytosis, leukostasis, priapism