Lymphoma--emerging realities in sub-Saharan Africa.

Substantial geographical differences exist for Hodgkin and other lymphoproliferative disorders with these having previously been documented in a report from the lymphoma reclassification project. In the light of rampant human immunodeficiency syndrome, largely centred in sub-Sahara, this experience is updated in a further 512 consecutive individuals treated over an 8-year period in a privately based academic centre. Median age was 55.2 years 61% were males, 10% had Hodgkin lymphoma and, overall, constitutional symptoms were present in 20%. Prior to referral 19% had received chemotherapy and a further 20% some form of irradiation. Median survival in hairy cell leukaemia (n=14), chronic lymphocytic leukaemia-small lymphocytic lymphoma (n=103), Hodgkin (n=41) and follicular lymphoma (n=59) was not reached at the time of analysis and exceeded 36 months. This was followed by 32 months for those with mantle cell (n=7), splenic (n=2) and extranodal marginal cell (n=11), 24 months for T-cell lymphomas (n=24), 20 months for diffuse large B-cell variants (n=88) but only 12 months for the aggressive tumours exemplified by Burkitt (n=7) and lymphoblastic subtypes (n=6). The remaining 36 patients had to be excluded because numbers were too small for statistical analysis or unreliable staging. Adverse factors were constitutional symptoms, prior treatment with chemotherapy, intermediate or high-risk scores as defined by the international prognostic index, histologic grading and certain anatomical sites of primary tumour. In contrast gender, staging by Rye or Rai classification, retroviral infection and prior treatment with radiotherapy were without effect. Overall survival at 3 years in each category was compared to the curve for the entire cohort and was 100% in hairy cell leukaemia receiving two chlorodeoxyadenosine and greater than 88% in Hodgkin lymphoma treated according to the German study group protocols (p=0.0004). Corresponding figures for chronic lymphocytic leukaemia-small lymphocytic lymphoma were 82% (p=0.0006), follicular lymphoma 71% (p=0.060), peripheral T-cell lymphoma 43% (p=0.0156), diffuse large B-cell lymphoma 39% (p<0.0001), aggressive tumours 25% (p=0.0002) and for the indolent categories including mantle cell, splenic and extra nodal marginal cell lymphomas 22% (p=0.2023). Outcome argues in favour of patient management by a multidisciplinary team implicit in which are standardised protocols for diagnosis, staging and treatment. Under these circumstances the well recognized centre effect applies when results approximate those from first world reference centres. Conversely any deviation from such a disciplined approach is unlikely to achieve comparable benefit and therefore to be strongly discouraged.

Within-subject variability and boosting of T-cell interferon-gamma responses after tuberculin skin testing.

RATIONALE: The optimal strategy for the diagnosis of latent tuberculosis infection is controversial. Adoption of a two-step strategy (tuberculin skin test [TST] followed by an IFN-gamma release assay [IGRA], compared with an IGRA alone), may be limited by TST-mediated boosting of subsequent IGRA responses. Assessment of within-subject IGRA variability will aid in establishing thresholds for conversions and reversions, and interpretation of serial testing results. OBJECTIVES: To determine short-term IGRA variability and the impact of TST on subsequent IGRA results. METHODS: Within-subject variability and TST-mediated boosting of IGRA responses were evaluated in 26 South African participants with varying exposure risk. IGRAs (T-SPOT.TB, QuantiFERON-TB Gold In-Tube [QuantiFERON-TB-GIT], PPD, and heparin-binding hemagglutinin) were repeated four times over 21 days pre-TST, and on Days 3, 7, 28, and 84 post-TST administration. MEASUREMENTS AND MAIN RESULTS: All participants showed within-subject IGRA variability. Changes of +/-3 spots (T-SPOT.TB) or +/-80% from the mean IFN-gamma response (QuantiFERON-TB-GIT) over 3 weeks explained 95% of the variability. Spontaneous conversions/reversions occurred in 7 of 26 subjects (27%) (6 for T-SPOT.TB and 1 for QuantiFERON-TB-GIT [P = 0.049]) during the within-patient variability studies (pre-TST). After the TST eight subjects (33%) boosted above the defined baseline variability. By Day 7 post-TST, but not Day 3, 2 (12.5%) initially IGRA-negative test subjects converted. By contrast, boosting of PPD and heparin-binding hemagglutinin occurred by Day 3 post-TST. CONCLUSIONS: When using a two-step screening strategy it appears safe to perform a QuantiFERON-TB-GIT or T-SPOT.TB IGRA within 3 days of performing the TST. A 3-spot or 80% IFN-gamma response variation, on either side of baseline values, explains 95% of the short-term variability and may be useful for interpreting conversions and reversions, and values close to the cut-point.

Immunohematopoietic stem cell transplantation in Cape Town: a ten-year outcome analysis in adults.

BACKGROUND AND OBJECTIVES: Immunohematopoietic stem cell transplantation has curative potential in selected hematologic disorders. Stem cell transplantation was introduced into South Africa in 1970 as a structured experimental and clinical program. In this report, we summarize the demography and outcome by disease category, gender, and type of procedure in patients older than 18 years of age who were seen from April 1995 to December 2002. PATIENTS AND METHODS: This retrospective analysis included 247 individuals over 18 years of age for whom complete data were available. These patients received grafts mostly from peripheral blood with the appropriate stem cell population recovered by apheresis. RESULTS: Patient ages ranged from 20 to 65 years with a median age of 42 years. There were 101 females and 146 males. There were no withdrawals and 63% survived to the end of the study. At 96 months of follow-up, a stable plateau was reached for each disease category. Median survival was 3.3 years (n=6, 14.6%) for acute lymphoblastic anemia, 3.1 years (n=44, 18%) for acute myeloid leukemia, 2.8 years (n=47, 19%) for chronic granulocytic leukemia, 2.8 years (n=71, 29%) for lymphoma, 1.5 years (n=23, 9%) for myeloma, 1.43 years (n=10, 4%) for aplasia, and 1.4 years (n=38, 15%) for a miscellaneous group comprising less than 10 examples each. Multivariate analysis showed that only diagnosis and age had a significant impact on survival, but these two variables might be interrelated. There was no significant difference in outcome by source of graft. CONCLUSION: The results confirm that procedures carried out in a properly constituted and dedicated unit, which meets established criteria and strictly observes treatment protocols, generate results comparable to those in a First World referral center. Low rates of transplant-related mortality, rejection and graft-versus-host disease are confirmed, but the benefits cannot be extrapolated outside of academically oriented and supervised facilities.

Pediatric immunohematopoietic stem cell transplantation at a tertiary care center in Cape Town.

UNLABELLED: INTRODUCTION AND STUDY DESIGN: We conducted a retrospective analysis of consecutive referrals of patients under 18 years of age undergoing immunohematopoietic stem cell transplantation to assess the influence of age, diagnosis, graft type and gender on survival. We also contrasted program activity and outcome to that reported from a state hospital in the same geographical area over a comparable period. METHODS: Conditioning employed either a sequential combination of fractionated 12Gy whole body and 6Gy total nodal irradiation separated by 120mg/kg of cyclophosphamide in patients over 15 years of age. Alternatively, the latter agent was combined initially with oral busulphan and later the intravenous equivalent. Neuroblastoma cases were prepared using a different regimen. In allografts the harvested product underwent ex vivo T-cell depletion with the humanized version of anti-CD 52 monoclonal antibody designated Campath 1H. No additional immunosuppression was given except where matched unrelated volunteer donors were employed. RESULTS: Sixty-eight procedures were carried out in 61 patients over a 6-year period. Of 11 with acute myeloid leukemia, 8 are alive and well whereas 8 of the 14 with the lymphoblastic variant have died. Of the remaining 12 with hematologic malignancy, all but 2 are alive. Ten of the 17 with aplasia are alive as are all with thalassemia or sickle cell disease. None of the four variables tested affected survival. CONCLUSION: Our analysis indicates that the standardized preparative regimen, coupled with a now well-established immunosuppressive regimen, is as effective in patients under 18 years of age as in adults. Our analysis also indicates that in a resource-scarce or developing country, it is mandatory to limit high-risk and relatively expensive procedures to active teams that enjoy international accreditation, whether these be in the state or private sector.

A single unit lymphoma experience: outcome in a Cape Town academic centre.

To document outcome in Hodgkin and other lymphomas from a privately based academic centre the clinical records from 253 consecutive referrals were analysed. Diagnosis was according to World Health Organization criteria, prognosis assigned by the international index and therapy risk-stratified with results subject to appropriate statistical methodology. None of these patients underwent transplantation. For the cohort the median age was 55 years (range 11-94) and 63% were male. Constitutional symptoms were present in 22%; a quarter had previous chemotherapy and a third some form of irradiation prior to referral. Fifty-seven percent were stage I or II and 21% had nodal disease above and below the diaphragm whilst in the remainder cells were present in the circulation and this included the subset of chronic lymphocytic leukaemia -- small lymphocytic lymphoma. Positron emission scanning was not available for these studies. Median survival for the cohort is 3.2 years and reduced to 1.3 years by the presence of unexplained fever, sweating or inappropriate weight loss. Further adverse factors included any prior treatment, intermediate or high-grade histopathology, risk factors defined by the International Prognostic Index as well as late Rai stages. Analysed by disease category Hodgkin lymphoma (n=17) when managed according to the German Study Group protocols and hairy cell leukaemia (n=10) treated with two chlorodeoxyadenosine -- both had a stable plateau in excess of 90%. The corresponding figures for follicular variants (n=31) was 72% in the low risk and 58% in the remainder when treated with cyclophosphamide, vincristine and prednisone. Curves for the aggressive or diffuse large B-cell lymphoma (n=44) fell initially to 48%, but relapse continued in stages III and IV to the current level of 18% when receiving cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone on the 21-day schedule. Chronic lymphocytic leukaemia -- small lymphocytic lymphoma (n=58) were initially given pulsed chlorambucil and sustained response was over 90% with low bulk, but declined to reach 30% as prognostic score rose. The miscellaneous categories (n<5 each) managed variably, but using the same criteria, were pooled and are presently at 62% and 30% for high and low grades. It is concluded that precise diagnosis, accurate staging and therapy on standardised risk-stratified programmes, delivered uniformly by a single multidisciplinary group, creates the all-important centre effect; matching figures are unlikely to apply outside these disciplined circumstances. The expectation from patients and referring physicians alike is that, since lymphomas are potentially curable, such an approach to comprehensive management will be regarded as standard even in an under resourced or Third World country. It follows that late referral and prior therapy will adversely affect performance status and compromise life span: These alternative approaches are inappropriate and strongly discouraged.