Research Articles (Haematological Pathology)

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An 8-year retrospective study of adult and paediatric Burkitt’s lymphoma at Tygerberg Hospital, South Africa
(AOSIS, 2020-04-30) Musekwa, Ernest; Chapanduka, Zivanai C.; Bassa, Fatima; Kruger, Mariana
Background: Burkitt lymphoma(BL) is a high grade non-Hodgkin lymphoma, which may be underdiagnosed in South Africa, due to a high burden of infectious diseases such as HIV and TB which may present with similar clinical features. Aim: To describe demographics and clinico-pathological characteristics of patients diagnosed with BL. Setting: Tygerberg Hospital (TBH), South Africa between 2007-2014. Methods: We performed a retrospective descriptive and survival analysis of patients diagnosed with BL at TBH between 01 January 2007 and 31 December 2014 with at least 24-month follow-up. Data was collected from the Tygerberg Lymphoma Study Group database and the South African Children Cancer Study Group Tumour Registry. Results: There were 73 patients with BL, of whom 68 were admitted to TBH and whose data was further analysed. The majority of patients were adults (74%). There was a female predominance in adults and a male predominance in children (p = 0.002). Various regimens were used in adults while a single treatment protocol was used in children. The proportion of patients with HIV and advanced BL was higher in adults than in children. The 2-year overall survival of the treatment group was 45%. The outcome of patients with BL in adults (34%) was poorer than that of children (69%) (p = 0.022). HIV negative patients had a non-significant survival advantage (57%) over HIV positive patients with 41% 2-year overall survival (p = 0.2876). Conclusion: This study demonstrates a better cure rate in children treated for BL compared to adults, with HIV-infection being a risk factor for poor outcome.
Adult T-cell leukaemia / lymphoma in an adolescent patient : expect the unexpected
(AOSIS, 2020-05-25) Abdullah, Ibtisam; Nell, Erica-Mari; Chapanduka, Zivanai C.
ENGLISH ABSTRACT: This case study explores a clinicopathological presentation of Adult T-cell leukaemia/lymphoma (ATLL) at Tygerberg Hospital; a disease associated with adulthood noted in an adolescent patient. Adult T-cell leukaemia–lymphoma oncogenesis develops through a multistep process with an accumulation of mutations. Infection through human T-lymphotropic virus type 1 (HTLV-1) is the first step of a multistep process resulting in eventual clonal proliferation of mature T-cells. There is a long latency period of 20–50 years from the time of infection with HTLV-1 to the development of symptoms of ATLL; thus, ATLL is a malignancy associated with adulthood. The median age of diagnosis is 58, ranging from the third to ninth decade of life. This is an ideal learning case as it highlights the importance of recognising ATLL in children and young adults in our population.
Age and race distribution of patients who undergo haematological investigations at Tygerberg Hospital (Afrikaans)
(HMPG, 1977-11) Brink S.; Van Schalkwyk D.J.; Steytler J.G.
The race, age and sex of patients referred for peripheral blood investigations at the Tygerberg Hospital were analysed statistically. An IBM 370/158 computer was used. Two groups were compared. The first was a 'low Hb group' of 2065 patients who had at least once during the first 6 months of 1976 had a haemoglobin (Hb) value of 10 g/dl or lower. The second, a 'hospital group' of 600 patients, was selected with the aid of tables for generating random numbers and was representative of the general hospital population. Rank order correlation methods using the ratios between the observed and the population percentages (based on the census figures for the Cape Peninsula) for the different age groups, between the race-age combinations, were used, and significant differences were found. In the hospital group the higher percentage of women between 20 and 39 years and the higher percentage of men older than 60 years was striking. In the low Hb group 38.8% of the patients were below 4 years of age, and 61% in the microcytic group (mean corpuscular volume (MCV) below 75 fl) were under the age of 6 years. The largest number of cases of iron-deficient anaemias in the hospital was therefore found in children. The MCV and Hb values had a fairly normal distribution, but in the macrocytic subdivision (MCV higher than 95 fl) of the low Hb group, White men were significantly over-represented. In the hospital group Hb and MCV values were slightly lower than the values accepted in a normal population, the mean MCV of women being lower than that of men (P < 0.01), and the values of non-Whites being lower than those of Whites.
Aplasia versus pancytopenia, including the pure red cell variant
(Health and Medical Publishing Group (HMPG), 2012-09) Jacobs, Peter; Wood, Lucille
This is the first in our third series of clinical vignettes that are centred on everyday presentations. Each emphasises practical aspects of team-based care, having relevance for general practitioners, specialists and paramedical professionals alike. Disorders arising in blood and bone marrow result in some of the commonest symptoms and signs for which patients seek medical advice. A carefully taken history and meticulous physical examination, complemented by thoughtful and judicious use of laboratory tests, provide the clinical basis for a working diagnosis. Advanced haematology may be needed to extend evaluation to the bone marrow and plasma while supplementary imaging or radionuclide technology further links primary care practitioner or specialist to the experienced haematologist. Such a multidisciplinary and fully interactive approach offers the preferred way to problem solving and optimum management.
An approach to the diagnosis and management of multiple myeloma
(South African Medical Association, 2019-09-30) Fazel, F.; Bassa, F.
ENGLISH ABSTRACT: Multiple myeloma (MM) is a plasma cell dyscrasia that accounts for ~10% of haematological malignancies. It is a disease of the elderly, with a slight male predominance. Almost all cases of MM are preceded by an asymptomatic, premalignant phase known as monoclonal gammopathy of undetermined significance (MGUS). The clinical presentation of MM may be nonspecific, with the most common presenting symptoms being fatigue, bone pain and anaemia. The diagnostic criteria for MM were revised in 2014 to include 3 specific biomarkers of malignancy that are associated with an increased risk of target organ damage. This has resulted in a paradigm shift in the management of MM. The introduction of immunomodulatory agents and proteasome inhibitors has significantly improved the survival of patients with MM. Autologous stem cell transplantation remains the standard of care in younger, fit patients, where there is also a clear role for maintenance chemotherapy. Transplant-ineligible patients benefit from a prolonged induction therapy, and the role of maintenance therapy in this setting is still unclear. Despite major advances in therapy, MM remains an incurable malignant condition and novel agents such as monoclonal antibodies play an important role, especially in the elderly and patients who have relapsed.
Association of deworming with reduced eosinophilia : implications for HIV/AIDS and co-endemic diseases
(Academy of Science of South Africa, 2003-04) Fincham, J. E.; Markus, M. B.; Adams, V. J.; Lombard, C. J.; Bentwich, Z.; Mansvelt, E. P. G.; Dhansay, M. A.; Schoeman, S. E.
Eosinophil counts in venous blood were monitored during a randomized controlled deworming trial (n = 155 children) that lasted for a year, and in a whole-school deworming programme (range 174-256 children) of 2 years' duration. Mean eosinophil counts (x109/I) decreased from 0.70 in the randomized trial, and 0.61 in the whole-school study, to well within the normal paediatric range of 0.05-0.45 (P < 0.05). The prevalence of eosinophilia declined from 57% to 37% in the randomized trial (mean for 400, 800 and 1200 mg albendazole doses); and from 47% to 24% in the whole-school study (500 mg stat mebendazole). Benzimidazole anthelminthics were highly effective against Ascaris but less so against Trichuris. Activated eosinophils are effector and immunoregulatory leucocytes of the T-helper cell type 2 (Th2) immune response to parasitic helminths and atopic disorders. Under conditions of poverty where soil-transmitted helminths are hyperendemic, Th2 polarization of the immune profile is characteristic. Regular anthelminthic treatment should reduce contact with worm antigens, and this may contribute to re-balancing of the immune profile. Suppression of eosinophil recruitment and activation, together with related cellular and molecular immunological changes, might have positive implications for prevention and treatment of co-endemic diseases, including HIV/AIDS, cholera, tuberculosis and atopic disorders.
B-cell and T-cell activation in South African HIV-1-positive non-Hodgkin’s lymphoma patients
(Medpharm Publications, 2018) Flepisi, Brian T.; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd
Background: Altered immune mechanisms play a critical role in the pathogenesis of non-Hodgkin’s lymphoma (NHL). HIV-1 (HIV) infection is associated with a state of excessive T-cell activation, which can lead to increased T-cell turnover and lymph node fibrosis. Objectives: This study aimed to determine the serum levels of circulating B-cell activation markers, and the expression of T-cell activation and regulatory markers in HIV-positive NHL patients. Method: The serum levels of circulating soluble(s) sCD20, sCD23, sCD27, sCD30 and sCD44 molecules, all of which are biomarkers of B-cell activation, were determined by enzyme-linked immunosorbent assays (ELISA), while biomarkers of T-cell activation (CD8+CD38+) and regulation (FoxP3) were determined by flow cytometry in 141 subjects who were divided into five groups: Combination antiretroviral therapy (ART)-naïve HIV-positive patients; ART-treated HIV-positive patients; HIV-negative NHL patients; HIV-positive NHL patients on ART; and healthy controls. Results: HIV-positive NHL patients had significantly higher serum levels of sCD20, sCD23, sCD30 and sCD44 than HIV-negative NHL patients, while all five biomarkers were significantly elevated in HIV-positive NHL patients when compared with ART-treated HIV-positive patients. HIV-positive NHL patients had higher CD8+CD38+ and lower FoxP3 expression than HIV-negative NHL and ART-treated HIV-positive patients. Conclusion: B-cell activation is increased in HIV-positive NHL patients and is associated with reduced regulatory T-cell populations and increased CD8+ T-cell activation.
Between a rock and a hard place : COVID-19 and South Africa’s response
(Oxford University Press, 2020) Staunton, Ciara; Swanepoel, Carmen; Labuschagine, Melodie
The spread of COVID-19 across China, Asia, Europe and the United States of America was met with public health responses that initially encouraged hand washing and social distancing. They quickly turned to restrictions on the freedom of movement and assembly in the form of forced isolation, mandatory quarantines and lockdowns. Africa’s first confirmed case was not until 14 February in Egypt and March saw a steady spread of the virus throughout the African continent. Concern began to rise about the impact that the virus would have on a continent that is currently facing HIV and TB epidemics and sporadic outbreaks of Ebola and Lassa Fever. There were fears that the already weakened health systems in many African jurisdictions may be unable to cope with another pandemic and quick and decisive action to stop the spread of the virus was considered to be essential. On 15 March 2020, nine days after the first recorded case in South Africa, President Cyril Ramaphosa announced a State of Disaster. Over the following weeks, a series of regulations were promulgated that limited the freedom of movement and assembly, limited the sale of certain items, specifically prohibited the sale and transportation of alcohol and cigarettes and criminalised the spread of disinformation on COVID-19. Together they represent the greatest limits on the Bill of Rights in post-apartheid South Africa. However, public health strategies such as social distancing and regular hand washing are a privilege many in South Africa cannot afford, especially for thosein crowded informal settlements and who use mass public transport systems. In this paper, we consider these regulations and argue that two major issues are a lack of a community informed response and an over-reliance on the criminal law to this major public health crisis.
Biomarkers of HIV-associated cancer
(Libertas Academica, 2014) Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd
Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin’s lymphoma, and invasive cervical cancer.
Bone marrow involvement in malignant lymphoma without peripheral lymphadenopathy
(HMPG, 1977-07) Staples, W. G.; Getaz, E. P.
Twelve cases of non-Hodgkin's lymphoma and a single case of Hodgkin's disease were first diagnosed on bone marrow biopsy. None of the patients had superficially enlarged lymph nodes, and in 3 patients the histological examination of the biopsy specimen showed normal reactive nodes. Eight patients were over the age of 60. The differential diagnosis from benign nodular lymphoid hyperplasia is discussed, with emphasis on the cytology and the paratrabecular position of the lymphoid infiltrate. Ten patients had focal involvement of the bone marrow and 1 of the 3 patients with diffuse involvement had Hodgkin's disease. Lymphoid nodules occur normally in the bone marrow and the authors conclude that non-Hodgkin's lymphoma and Hodgkin's disease can arise primarily in the bone marrow.
Castleman’s disease in the HIV-endemic setting
(Dove Medical Press, 2018) Mahroug, Esam-Rajab; Sher-Locketz, Candice; Desmirean, Minodora-Silvia; Abayomi, Emmanuel-Akinola; Tomuleasa, Ciprian; Grewal, Ravnit
Introduction: Castleman’s disease (CD), first described by Benjamin Castleman in 1954, is a giant or angiofollicular lymph node hyperplasia, described as a rare monotypic polyclonal B-cell lymphoproliferative disorder with an incompletely understood pathogenesis and variable clinical behavior. This study aimed to determine the incidence of CD diagnosis over an 11-year period. Additionally, the study aimed to describe the demographic, laboratory, and pathological features of CD. Methods: This is a retrospective study where the demographic and laboratory data were retrieved from the Tygerberg Academic Hospital (TAH) patient electronic records and Tygerberg Lymphoma Study Group (TLSG) and statistical analysis performed on the patients diagnosed with CD. Results: Fifty-four patients were diagnosed with CD during this period. The median age at presentation was 39 years (range: 9–58). HIV serology was available in 53 patients, of which 51 were HIV-positive and two were HIV-negative. The history of initiation of antiretroviral therapy at diagnosis was available in 43 patients (38 on treatment, four were not on treatment, and one defaulted treatment). The median CD4 count was 232.50 cells/μL (range: 2–883). The HIV viral load was performed in 43 patients at diagnosis, which was <49 HIV-1 RNA copies/μL in more than half of the patients (58%). Diagnosis was made on lymph node biopsies in 53 patients, with one case diagnosed on a spleen biopsy. Kaposi sarcoma was found on the same tissue biopsy in 13 cases. A bone marrow biopsy was performed in 31 patients. The predominant features noted were a disorganized hypercellular marrow with plasmocytosis. Conclusion: CD is a rare polyclonal B-cell lymphoproliferative disorder. However, we demonstrated a significant increase in the incidence of HIV-associated multicentric CD over the last decade in our area in South Africa.
Chronic myelomonocytic leukaemia: a case report
(HMPG, 1977) Getaz E.P.; Staples W.G.
[No abstract available]
Clinical and haematological problems associated with severe abruptio placentae
(Health & Medical Publishing Group, 1978) Odendaal H.J.; Brink S.; Steytler J.G.
A clinical study was done of 80 patients in whom abruptio placentae was severe enough to cause intra-uterine death of the fetus. Central venous pressure was measured whenever possible to ensure adequate fluid replacement. Although the minority of the patients were shocked when admitted, blood replacement averaged 5 units per patient. The caesarean section incidence was 21%. Only 1 patient developed renal failure for which peritoneal dialysis was done. No maternal deaths occurred. Serial coagulation studies were done in 58 patients. Diffuse intravascular coagulation was present in the majority. After delivery of the fetus, however, tests became normal.
Complete blood count reference intervals from a healthy adult urban population in Kenya
(Public Library of Science, 2018) Omuse, Geoffrey; Maina, Daniel; Mwangi, Jane; Wambua, Caroline; Radia, Kiran; Kanyua, Alice; Kagotho, Elizabeth; Hoffman, Mariza; Ojwang, Peter; Premji, Zul; Ichihara, Kiyoshi; Erasmus, Rajiv
Background: There are racial, ethnic and geographical differences in complete blood count (CBC) reference intervals (RIs) and therefore it is necessary to establish RIs that are population specific. Several studies have been carried out in Africa to derive CBC RIs but many were not conducted with the rigor recommended for RI studies hence limiting the adoption and generalizability of the results. Method: By use of a Beckman Coulter ACT 5 DIFF CP analyser, we measured CBC parameters in samples collected from 528 healthy black African volunteers in a largely urban population. The latent abnormal values exclusion (LAVE) method was used for secondary exclusion of individuals who may have had sub-clinical diseases. The RIs were derived by both parametric and non-parametric methods with and without LAVE for comparative purposes. Results: Haemoglobin (Hb) levels were lower while platelet counts were higher in females across the 4 age stratifications. The lower limits for Hb and red blood cell parameters significantly increased after applying the LAVE method which eliminated individuals with latent anemia and inflammation. We adopted RIs by parametric method because 90% confidence intervals of the RI limits were invariably narrower than those by the non-parametric method. The male and female RIs for Hb after applying the LAVE method were 14.5±18.7 g/dL and 12.0± 16.5 g/dL respectively while the platelet count RIs were 133±356 and 152±443 x103 per μL respectively. Conclusion: Consistent with other studies from Sub-Saharan Africa, Hb and neutrophil counts were lower than Caucasian values. Our finding of higher Hb and lower eosinophil counts compared to other studies conducted in rural Kenya most likely reflects the strict recruitment criteria and healthier reference population after secondary exclusion of individuals with possible sub-clinical diseases.
Cystic partially differentiated nephroblastoma-like lesion following neoadjuvant chemotherapy for nephroblastoma : a case report and review of the literature
(Elsevier, 2020) Bruce-Brand, C.; Reyes-Mugica, M.; Van Zyl, A.; Schubert, P. T.
Cystic partially differentiated nephroblastoma (CPDN) and cystic nephroblastoma are paediatric renal tumours characterised by the presence of a variable combination of primitive epithelium, immature stroma and blastema. Cystic nephroblastoma can be identified by the presence of solid expansile areas of tumour which are absent in CPDN. The distinction can pose diagnostic difficulty pre-operatively and is of paramount importance as their metastatic potential, prognosis and hence therapeutic strategies differ. We present a 2 year old girl, with two right renal masses, diagnosed pre-operatively as synchronous nephroblastoma based on clinical, radiological and cytologic findings. Neo-adjuvant chemotherapy was administered followed by nephrectomy. Two discrete tumours were present, one being an epithelial predominant nephroblastoma and the other a CPDN. The CPDN showed an unusual spectrum of epithelial cells lining the cysts including intestinal type epithelium with goblet cells. This case represents one of three cases described thus far in the literature of concomitant nephroblastoma and CPDN or cystic nephroma (CN) and is the only case in which nephroblastoma occurred synchronously with CPDN. Due to neo-adjuvant therapy being instituted for the nephroblastoma, this case provides unique insights into possible chemotherapy induced changes in a CPDN (usually treated by surgical excision alone). This case highlights several important issues in paediatric cystic renal neoplasms, particularly the distinction between cystic nephroma, CPDN and cystic nephroblastoma. The differential diagnosis of cystic paediatric renal neoplasms is broad and requires appropriate clinical, radiological and histological assessment, often with ancillary immunohistochemical and molecular studies to arrive at a correct diagnosis. Histologic features of chemotherapy effect, although well-described in nephroblastoma, are not well-described in CPDN. Based on our knowledge of possible chemotherapy induced changes in nephroblastoma, such as maturation of epithelial and stromal elements that may be so marked as to mimic mature teratoma, we hypothesize that this case demonstrates such changes within a CPDN.
Disseminated tuberculosis, bone marrow necrosis and lymphoma : a case report
(Health & Medical Publishing Group, 1977) Staples, W. G.; Getaz, E. P.; Botha, D.
Tuberculosis often complicates lymphoma, and bone marrow necrosis has been described in disseminated tuberculosis. However, the association of lymphoma, disseminated tuberculosis and bone marrow necrosis is rare. We report a patient with this triple association. After a 3-week influenza-like illness the patient was admitted to hospital semicomatose with pancytopenia and hyponatraemia. During routine examination a bone marrow trephine biopsy revealed diffuse lymphomatous infiltration with scattered necrotic foci. On Ziehl-Neelsen staining these foci exhibited numerous acid-fast bacilli. The patient subsequently died and at autopsy was found to have widely disseminated non-reactive tuberculosis.
Effects of puff adder venom on coagulation, fibrinolysis and platelet aggregation in the baboon
(Health and Medical Publishing Group (HMPG), 1974) Brink, S.; Steytler, J. G.
The in vitro and in vivo hematological effects of puff adder (Bitis arietans) venom in the baboon (Papio ursinus) with regard to its effect on coagulation, fibrinolysis and platelet aggregation were studied. There is a delay in the intrinsic coagulation mechanism with fibrinolysis and in vitro fibrinogenolysis. Normal human platelets demonstrated an extreme susceptibility to puff adder venom in vitro. The aggregation of platelets with small dosages of venom was irreversible. The effect is related to the dosage, and appears to be the result of multiple enzyme activities, some of which are heat labile. In minimal amounts there is evidence of consumption of blood coagulation factors with sustained thrombocytopenia, but no fibrinolysis, where heparin therapy might have a beneficial effect. With larger dosages of venom the thrombocytopenia, hemorrhagic effects and shock are not prevented or corrected by heparin and heparinisation might even be harmful. The effect of heparin should be further investigated, since it might have a place in mildly affected cases of snakebite, where absorption into the blood has been slow or intermittent. It might be indicated when antivenene is not available or when patients are sensitive to serum.
'n Epidemiologiese studie van perifere bloedondersoeke
(HMPG, 1979-08) Brink S.; Van Schalkwyk, D. J.
A statistical random sample of 600 patients from the population referred to Tygerberg Hospital for peripheral blood investigations was analysed statistically with an IBM 370/158 computer. Suitable transformations were used for normalization of the data. The results of Coulter Model S investigations, platelet counts (Coulter F), erythrocyte sedimentation rates, differential counts (with regard to neutrophil, Iymphocyte, monocyte and eosinophil counts), age, race and sex of the patients, as well as possible associations between the day of the week and the haematological tests were investigated independently for each of the four race and sex groups, i.e. White men, White women, non-White men and non-White wo- Ontvangsdatum: Februarie 1979. men. Machine sorting was used to obtain graphs representing the mean values of 12 haematological variables versus age in the four race and sex groups. Regression analysis between the different variables was done, and mean values are reported. Normal haematological limits (-+- 2 standard deviations) for the different age groups were used, and with machine processing the results were evaluated as low, normal or high in order to obtain a table for the visualization of a normal or abnormal distribution, skewness to the right or left, and percentages of abnormal values for each variable for each of the different age groups in the four race and sex groups. In this study we investigated a selected group of patients. No conclusions with regard to 'normal' values can be made, but, with the use of statistical computing of routine numerical data, an approach to epidemiology is demonstrated
Familial Waldenstrom's macroglobulinaemia: a case report
(HMPG, 1977-06) Getaz, E. P.; Staples, W. G.
A patient with Waldenstrom's macroglobulinemia, whose father died of the same condition, is presented. The literature on familial occurrence of paraproteinaemia is briefly reviewed.
Guideline for the treatment of myelodysplastic syndromes (MDS) in South Africa
(Health and Medical Publishing Group (HMPG), 2011-12) Louw, V. J.; Bassa, F.; Chan, S. W.; Dreosti, L.; Du Toit, M.; Ferreira, M.; Gartrell, K.; Gunther, K.; Jogessar, V.; Littleton, N.; Mahlangu, J.; McDonald, A.; Patel, M.; Pool, R.; Ruff, P.; Schmidt, A.; Sissolak, G.; Swart, A.; Verburgh, E.; Webb, M. J.
Introduction. Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal haematopoietic disorders characterised by chronic and progressive cytopenias resulting from ineffective haematopoiesis. Treatment is complicated by differences in disease mechanisms in different subgroups, variable clinical phenotypes and risk of progression to acute myeloid leukaemia. Rationale. Changes in disease classification, prognostic scoring systems, the availability of novel treatment options and the absence of South African guidelines for the diagnosis and management of these complex disorders underpinned the need for the development of these recommendations. Methods. These recommendations are based on the opinion of a number of experts in the field from the laboratory as well as clinical settings and came from both the private and institutional academic environments. The most recent literature as well as available guidelines from other countries were discussed and debated at a number of different meetings held over a 2-year period. Results. A comprehensive set of recommendations was developed focusing on risk stratification, supportive management and specific treatment. Novel agents and their indications are discussed and recommendations are made based on best available evidence and taking into account the availability of treatments in South Africa. Conclusion. Correct diagnosis, risk stratification and appropriate therapeutic choices are the cornerstones of success in the management of patients with MDS.

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