Hematological Complications of Human Immunodeficiency Virus (HIV) Infection: An Update From an HIV-Endemic Setting.

Medical professionals, particularly in regions with a high burden of human immunodeficiency virus (HIV), should be alert to the hematological complications of HIV, which may include cytopenias, malignancy, and coagulation disturbances. Patients may present with these conditions as the first manifestation of HIV infection. Hematological abnormalities are often multifactorial with opportunistic infections, drugs, malignancy, and HIV infection itself contributing to the clinical presentation, and the diagnosis should consider all these factors. Life-threatening hematological complications requiring urgent diagnosis and management include thrombotic thrombocytopenic purpura, superior mediastinal syndrome, spinal cord compression, and tumor lysis syndrome due to aggressive lymphoma. Antiretroviral therapy is the therapeutic backbone, including for patients with advanced HIV, in addition to specific therapy for the complication. This article reviews the impact of HIV on the hematological system and provides a clinical and diagnostic approach, including the role of a bone marrow biopsy, focusing on perspectives from sub-Saharan Africa.

Cytogenetically Normal Acute Myeloid Leukaemia at a Single Centre in South Africa.

BACKGROUND AND OBJECTIVES: The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukemia (CN-AML) renders it an ongoing therapeutic challenge. The European LeukemiaNet (ELN) 2017 guidelines attempted to address this by guiding post-remission therapy according to six prognostically informative mutations. However, its applicability in a South African setting remains unclear due to limited local data. This retrospective study aimed to describe a South African CN-AML cohort according to clinicopathological and molecular features as well as treatment outcomes and, consequently, to investigate the local applicability of a triple-mutation testing approach for risk stratification in accordance with the ELN 2017 guidelines, using nucleophosmin 1 (NPM1), fms-related receptor tyrosine kinase 3 internal tandem duplication (FLT3-ITD), and CCAAT enhancer-binding protein alpha (CEBPA) mutation status. MATERIALS AND METHODS: A review of cytogenetic results for adult de novo AML cases diagnosed at Groote Schuur Hospital between 2005 and 2018 was performed. CN-AML cases were further characterized via a review of clinical and laboratory data and additional molecular testing on stored DNA samples to allow for mutation-based risk stratification and outcome analysis. RESULTS: In total, 218 patients with AML were identified, of which 33% were cytogenetically normal. NPM1, FLT3-ITD, and CEBPA mutations were found in 39%, 34%, and 9% of CN-AML cases, respectively. Retrospective risk stratification according to mutations in these three genes accurately identified both patients at a high risk of induction-resistant disease and those who required an allogeneic stem cell transplant in their first complete remission. CONCLUSION: Local rates of CN-AML and associated NPM1 and FLT3-ITD mutations were comparable to those of European cohorts. Limited mutation analysis in the form of triple-mutation testing proved to be an economical and therapeutically informative prognostication approach for CN-AML in a resource-limited setting.

The International Prognostic Score and HIV status predict red cell concentrate transfusion needs in Hodgkin lymphoma.

Despite the burden of anemia among Hodgkin lymphoma (HL) patients, data evaluating red cell concentrate transfusion are limited. We retrospectively studied 285 newly diagnosed HL patients who received first-line adriamycin, bleomycin sulfate, vinblastine sulfate, and dacarbazine (ABVD) treatment at Groote Schuur Hospital, Cape Town. HIV prevalence in the cohort was 39.5% and 74.2% of patients had advanced stage HL. Patient prognosis was scored using the HL International Prognostic Score (IPS-7) and HL IPS-3. Seventy (24.6%) patients were transfused with a median of 2 (IQR 1-5) units per patient. Compared to HIV-negative patients, more HIV-positive patients were transfused (14.1% vs. 40.4%, p < .001) and received more units, median 2 (IQR 1-3) vs. 3 (IQR 2-5), p = .035. HL IPS-7 (OR 2.1, p < .001) and HL IPS-3 (OR 2.6, p < .001) were independently associated with transfusion. HL IPS-7, HL IPS-3, and HIV positivity remained associated with transfusion after adjusting for covariates. For patients with newly diagnosed HL, HL IPS-7, HL IPS-3, and HIV status predicted transfusion.

Focused investigations to expedite cancer diagnosis among patients with lymphadenopathy in a tuberculosis and HIV-endemic region.

PURPOSE: In tuberculosis (TB)-endemic areas, lymphadenopathy is frequently due to TB adenitis, but lymphoma and cancers are important differential diagnoses and critical to diagnose at the earliest opportunity. Key obstacles to lymphoma diagnosis include empiric TB treatment and difficulty accessing a biopsy. We report on a specialized clinic utilizing high-yield investigations for patients with lymphadenopathy. METHODS: This prospective interventional study investigated the utility of a core biopsy and the Xpert MTB/RIF Ultra (Ultra) on fine-needle aspirate (FNA) and tissue in a newly established lymph node biopsy clinic over 4 years. Electronic referral facilitated patient assessment within a week. Hematology fellows without specialist surgical or radiological expertise performed the biopsy on the first visit. RESULTS: In 277 patients, including 43% people with HIV, TB was the most frequent diagnosis (34%), followed by lymphoma (27%) and other cancers (17%). Patients were seen a median of 5 days [interquartile range (IQR) 2-8.5 days] from referral. Core biopsy provided sufficient tissue for diagnosis in 96% of patients with lymphoma (72/75) and 94% of patients with cancer (44/47). FNA Ultra had a sensitivity of 73.9% [34/46; 95% confidence interval (CI) 58.9-85.7], and tissue Ultra 73% (46/63; 95% CI 60.3-83.4). There were six false-positive Ultra tests, highlighting the value of histology to either support TB or make an alternative diagnosis. CONCLUSION: Core biopsies collected under the conditions described are safe and sensitive and can yield a rapid diagnosis. Combining Ultra and a core biopsy can accurately diagnose TB and cancer. This clinic provides an implementation model for resource-constrained and TB-endemic areas.

A comprehensive overview of pneumococcal vaccination recommendations for adults in South Africa, 2022.

Pneumococcal infections remain a common global cause of significant morbidity and mortality. The first recommendations for adult pneumococcal vaccination, published in South Africa in 1999, contained information only on the 23-valent polysaccharide vaccine (PPV23). With the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in adults and the perceived uncertainty that most clinicians had regarding use of these vaccines in adults, these vaccine recommendations were updated in 2022. A Working Group, which consisted of individuals in various fields of medical practice in South Africa, who were from different areas of the country, and included clinicians from both the public and private sectors, was assembled to revise the recommendations. The expertise of the participants varied widely, dependent on their training and specialty, and encompassed different organ systems, disease conditions, and/or practice types. Each participant was allocated a different section, based on their expertise, for which they were required to do an extensive review of the current literature and write their section. The entire working group then reviewed the complete document several times, following additional comments and recommendations. This update contains recommendations for the use of both PPV23 and PCV13, either alone, or in sequence, both in vaccine naïve and in previously vaccinated individuals. It includes both age and risk categories, and encompasses the elderly (≥65 years), as well as younger adults (<65 years) with comorbid conditions or with high-risk conditions and/or immunocompromise. It is hoped that this review and its associated vaccine recommendations will clarify for clinicians, from all spheres of practice in South Africa, how, where, and when pneumococcal vaccines should be used in adults, with the ultimate goal of significantly increasing the appropriate use of these vaccines, in order to decrease the substantial morbidity and mortality associated with pneumococcal infections in adults in South Africa. Furthermore, it is hoped that this review of local epidemiological data and the manner in which this information was interpreted in the development of these local vaccine recommendations, could be used as an example for other regions of the world, to tailor their recommendations to locally available epidemiological data.

Plasmablastic lymphoma: An update.

Plasmablastic lymphoma (PBL) is a highly aggressive B cell non-Hodgkin lymphoma frequently associated with immunosuppression, particularly human immunodeficiency virus (HIV) infection. Although PBL is rare globally, South Africa has a high burden of HIV infection leading to a higher incidence of PBL in the region. Laboratory features in PBL may overlap with plasmablastic myeloma and other large B cell lymphomas with plasmablastic or immunoblastic morphology leading to diagnostic dilemmas. There are, however, pertinent distinguishing laboratory features in PBL such as a plasma cell immunophenotype with MYC overexpression, expression of Epstein-Barr virus-encoded small RNAs and lack of anaplastic lymphoma kinase (ALK) expression. This review aims to provide a summary of current knowledge in PBL, focusing on the epidemiology, pathophysiology, laboratory diagnosis and clinical management.

Predictors of poor haematopoietic stem cell mobilisation in patients with haematological malignancies at a South African centre.

BACKGROUND: Autologous stem cell transplant (ASCT) is an established consolidation strategy in the treatment of haematological malignancies, however poor mobilisation (PM) can contribute to patient morbidity and high resource utilisation. Identifying the incidence, risk factors for PM and engraftment outcomes are important goals in our resource limited setting. METHODS: We retrospectively analyzed patients with haematological malignancies that consecutively underwent ASCT at Groote Schuur hospital, Cape Town, South Africa from January 2013 to January 2019. RESULTS: 146 patients - majority with multiple myeloma (MM)(41,8%), F:M= 1:2, underwent leukapheresis with median age of 32 years (range, 9 - 66 years). PM occurred in 25/146 (17%), mobilisation failure (MF) in 3/146 (2%) and super mobilisation (SMs) in 99/146 (68%), respectively. Risk factors for PM were: diagnosis of acute leukaemia (RR = 25, 95% CI 3.4 - 183, p = 0.002) and Hodgkin lymphoma (RR = 19, 95% CI 2.6 - 142, p = 0.004); low white cell count (WCC) at harvest (WCC < 9 × 109/L (RR=4.3, 95% CI 2.3 - 8.3, p < 0.0001) and two vs one line of prior therapy (RR = 3.1, 95% CI 1.45 - 6.7, p = 0.0037). Median days to neutrophil and platelet engraftment were 14 days (95% CI 14-15 days) and 16 days (95% CI 15-16 days) respectively. CONCLUSION: PM occurred in 17% of a contemporary South African ASCT cohort, albeit with a low MF rate (2%). There was surprisingly high rate (68%) of SMs, possibly reflective of superfluous mobilisation strategy in MM patients. We identified predictive factors for PM that will lead to enhanced cost-effective use of plerixafor.

Is Haploidentical Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide Feasible in Sub-Saharan Africa?

Identifying a suitable volunteer unrelated donor (UD) in South Africa is challenging due to the highly diverse ethnic groups and mixed-race populations in this region. Haploidentical hematopoietic cell transplantation (haploHCT) is thus an attractive procedure for patients with high-risk hematologic malignancies. This study was conducted to assess the safety and feasibility of haploHCT in South Africa. We retrospectively analyzed the outcome of 134 patients with hematologic malignancies who received unmanipulated haploHCT with post-transplantation cyclophosphamide at 2 high-volume HCT centers between 2014 and 2019. We assessed overall survival (OS), disease-free survival (DFS), nonrelapse mortality (NRM), relapse incidence (RI), and incidence of acute GVHD. The median recipient age was 44 years (range, 15 to 73 years) and the median donor age was 36 years (range, 9 to 68 years). Acute myelogenous leukemia or myelodysplastic syndrome (AML/MDS) and acute lymphoblastic leukemia (ALL) were the most common indications for haploHCT (61.2%). The European Society for Blood and Marrow Transplantation risk score was ≥5 in 44 patients (32.8%). Seventy-seven patients (57.4%) received a myeloablative conditioning regimen. The majority of patients received a sex-matched transplant (57.4%) and had peripheral blood stem cells (PBSCs) as the stem cell source (70.9%). Sixteen patients (11.9%) had an incongruent cytomegalovirus serostatus at transplantation. The median duration of follow-up was 10.8 months (range, 0.36 to 70.8 months). OS was 56% (95% confidence interval [CI], 47% to 64%) at 1 year and 37% (95% CI, 28% to 47%) at 3 years. DFS was 47% (95% CI, 38% to 55%) at 1 year and 32% (95% CI, 24% to 41%) at 3 years. The 100-day and 3-year cumulative incidence of NRM was 18% (95% CI, 11% to 25%) and 41% (95% CI, 32% to 50%), respectively, and the 1- and 3-year cumulative RI was 16% (95% CI, 11% to 24%) and 21% (95% CI, 14% to 29%), respectively. The 1-year OS was 55% (95% CI, 40% to 67%) for the patients with AML/MDS versus 41% (95% CI, 21% to 60%) for those with ALL. Forty-five patients (41.7%) developed acute GVHD by day +100; of these, 80% had grade I-II disease. Fifty patients (37.5%) developed cytomegalovirus infection that required therapy. On multivariable analysis, older donor age was an independent risk factor for lower DFS. RI was higher for diagnoses other than acute leukemia/MDS (relative risk [RR], 2.62; 95% CI, 1.12 to 6.15; P = .027), decreased for PBSC versus bone marrow (RR, 0.43; 95% CI, 0.19 to 0.95; P = .038) and decreased for offspring donors (RR, 0.25; 95% CI, 0.09 to 0.67; P = .006). These data support the feasibility of haploHCT and suggest that unmanipulated haploHCT using a younger parent or offspring donor is a viable option for adults in sub-Saharan Africa with acute leukemia and MDS who lack a suitable related or unrelated donor.

Patient blood management and blood conservation - Complimentary concepts and solutions for blood establishments and clinical services in South Africa and beyond.

Blood transfusions come with risks and high costs, and should be utilized only when clinically indicated. Decisions to transfuse are however not always well informed, and lack of clinician knowledge and education on good clinical transfusion practices contribute to the inappropriate use of blood. Low and middle-income countries in particular take much strain in their efforts to address blood safety challenges, demand-supply imbalances, high blood costs as well as high disease burdens, all of which impact blood usage and blood collections. Patient blood management (PBM), which is a patient-focused approach aimed at improving patient outcomes by preemptively diagnosing and correcting anaemia and limiting blood loss by cell salvage, coagulation optimization and other measures, has become a major approach to addressing many of the challenges mentioned. The associated decrease in the use of blood and blood products may be perceived as being in competition with blood conservation measures, which is the more traditional, but primarily product-focused approach. In this article, we hope to convey the message that PBM and blood conservation should not be seen as competing concepts, but rather complimentary strategies with the common goal of improving patient care. This offers opportunity to improve the culture of transfusion practices with relief to blood establishments and clinical services, not only in South Africa and LMICs, but everywhere. With the COVID-19 pandemic impacting blood supplies worldwide, this is an ideal time to call for educational interventions and awareness as an active strategy to improve transfusion practices, immediately and beyond.

Outcomes for Patients With Acute Promyelocytic Leukemia in South Africa.

BACKGROUND: The characteristics and outcomes of patients with acute promyelocytic leukemia (APL) from sub-Saharan Africa have not been published. PATIENTS AND METHODS: We report retrospectively on consecutively diagnosed APL patients treated in Cape Town, South Africa, during 1998-2019. A total of 69 patients were treated, of whom 27 (39%) were classified as having high risk APL. RESULTS: Early death rates at 7 and 30 days were 7% and 13%, respectively, including 4 patients who died before any treatment could be administered. Overall survival at 3 years was 76.5% (95% confidence interval, 63.9-85.2) for the entire cohort, and 82.5% (95% confidence interval, 69.7-90.2) if patients who died within 7 days of diagnosis were excluded. For 13 patients (18.8%), there was a delay of 5 or more days from time of initial presentation at a peripheral hospital until arrival at the leukemia center and administration of all-trans retinoic acid; only 1 of these patients died within 30 days. CONCLUSION: Despite the challenges faced in the public healthcare system of a developing country, outcomes of APL patients treated at our center are similar to outcomes from developed countries.

Diagnosing lymphoma in the shadow of an epidemic: lessons learned from the diagnostic challenges posed by the dual tuberculosis and HIV epidemics.

Infectious disease epidemics may overshadow and exacerbate existing challenges in diagnosing lymphoma. We describe pragmatic strategies we have implemented to overcome diagnostic obstacles caused by the local tuberculosis (TB) and HIV epidemics in South Africa, which may serve as a guide to minimize diagnostic delay during the COVID-19 pandemic. We report on the diagnostic utility of a rapid-access lymph node core-biopsy clinic, where lymph node biopsies are taken from outpatients at their first visit. Analysis of tissue biopsies (n = 110) revealed the three most common conditions diagnosed were TB adenitis (34%), lymphoma (29%), and disseminated malignancy (20%). A first-attempt core-biopsy was able to diagnose lymphoma in 27/32 (84%) of cases. Compared with a historical cohort, the diagnostic interval (time from first health visit to diagnostic biopsy) for patients with lymphoma was significantly shorter, 13.5 vs 48 days (p = 0.002).

HIV-associated and idiopathic-acquired haemophilia A: A single-centre case series from Cape Town, South Africa.

Acquired haemophilia A is a rare coagulation disorder, which can lead to life-threatening haemorrhages if not identified and treated promptly. It is characterised by the presence of autoantibodies (inhibitors) to factor VIII. Acquired haemophilia A associated with HIV is a rare but well described phenomenon with limited directions to its management. We comparatively describe four patients - two with HIV and two without - that presented with unusual bleeding episodes with a prolonged activated partial thromboplastin time secondary to factor VIII inhibitors. An empiric observation is that the patients with acquired haemophilia A associated with HIV had higher antibody titres at presentation, that required more prolonged immunosuppressive therapy to induce remission.

Diffuse large B-cell lymphoma in a South African cohort with a high HIV prevalence: an analysis by cell-of-origin, Epstein-Barr virus infection and survival.

Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is subdivided according to the cell-of-origin (COO) classification into germinal centre B-cell (GCB) and activated B-cell (ABC) subtypes, each with different molecular profiles and clinical behaviour. This study aims to describe the pattern of the COO subtypes, the proportion of Epstein-Barr virus (EBV) co-infection, and their influence on survival outcomes in a setting of high HIV prevalence. This retrospective cohort study included patients diagnosed with de novo DLBCL NOS at our tertiary academic centre in Cape Town, South Africa over a 14-year period. Immunohistochemical stains were performed for COO classification, according to the Hans algorithm. Tumour EBV co-infection was established by EBV-encoded ribonucleic acid in situ hybridisation (EBER-ISH) staining. The effect of the COO subtypes and EBV co-infection on overall survival were described by means of univariate, bivariate and multivariate analyses. A total of 181 patients with DLBCL NOS were included, which comprised 131 HIV-uninfected and 50 HIV-infected patients. There was an equal distribution of GCB and ABC subtypes in the HIV-infected and HIV-uninfected groups. EBV co-infection was detected in 16% of the HIV-infected cases and in 7% of the HIV-uninfected cases (p=0.09). There was no significant difference in the incidence of EBV co-infection between the GCB and ABC subtypes (p=0.67). HIV-infected patients with CD4 ≥150 cells/mm3 had similar survival to HIV-uninfected patients (p=0.005). Multivariate regression analysis showed that in the HIV-infected group with marked immunosuppression (CD4 <150 cells/mm3), there was significantly poorer overall survival compared to the HIV-uninfected group (HR 2.4, 95% CI 1.3-4.1). There were no statistically significant differences in overall survival by DLBCL COO subtype. There was no difference in the proportion of DLBCL COO subtypes, regardless of HIV status. EBV co-infection was more common in the HIV-infected group, but less than described in the literature. Unexpectedly, there were no significant differences in survival outcomes between the GCB and ABC subtypes. Higher CD4 counts in the HIV-infected group had good survival outcomes, while lower CD4 counts predicted adverse survival outcomes. Further research is needed to explore the genetic mutational landscape of HIV-associated DLBCL.

Correction to: Diagnostic accuracy of the Xpert MTB/Rif Ultra for tuberculosis adenitis.

After publication of the original article [1], we were notified that there is a mistake in the article note.

Diagnostic accuracy of the Xpert MTB/Rif Ultra for tuberculosis adenitis.

BACKGROUND: The WHO recently recommended the new Xpert MTB/RIF Ultra assay (Ultra) instead of the Xpert MTB/RIF assay because Ultra has improved sensitivity. We report the diagnostic accuracy of Ultra for tuberculous adenitis in a tuberculosis and HIV endemic setting. METHODS: We obtained fine-needle aspirates (FNA) and lymph node tissue by core-needle biopsy in adult patients with peripheral lymphadenopathy of >20 mm. Ultra and mycobacterial culture were performed on FNA and tissue specimens, with histological examination of tissue specimens. We assessed the diagnostic accuracy of Ultra against a composite reference standard of 'definite tuberculosis' (microbiological criteria) or 'probable tuberculosis' (histological and clinical criteria). RESULTS: We prospectively evaluated 99 participants of whom 50 were HIV positive: 21 had 'definite tuberculosis', 15 'probable tuberculosis' and 63 did not have tuberculosis (of whom 38% had lymphoma and 19% disseminated malignancy). Using the composite reference standard the Ultra sensitivity on FNA was 70% (95% CI 51-85; 21 of 30), and on tissue was 67% (45-84; 16/24) these were far superior to the detection of acid-fast bacilli on an FNA (26%; 7/27); AFB on tissue (33%; 8/24); or tissue culture (39%; 9/23). The detection of granulomas on histology had high senstivity (83%) but the lowest specficity. When compared with culture the Ultra on FNA had a sensitvity of 78% (40-97; 7/9) and tissue 90% (55-100; 9/10). CONCLUSIONS: Ultra performed on FNA or tissue of a lymph node had good sensitivity and high specificity. Ultra had a higher yield than culture and has the advantage of being a rapid test. Ultra on FNA would be an appropriate initial investigation for lymphadenopathy in tuberculosis endemic areas followed by a core biopsy for histopathology with a repeat Ultra on tissue if granulomas are present.

The determinants and impact of diagnostic delay in lymphoma in a TB and HIV endemic setting.

BACKGROUND: Little is known about the pathway to diagnosis of lymphoma in Sub-Saharan Africa, despite the increased risk of lymphoma in people living with HIV (PLHIV). The challenges of diagnosis in this setting include diagnostic confusion with extrapulmonary tuberculosis (EPTB), which commonly causes lymphadenopathy in PLHIV. METHODS: We analysed the time to diagnosis and treatment in patients using predetermined time intervals. Univariate and multivariable analyses were performed to determine the relationship between patient and disease-specific variables with delays to diagnosis. We were particularly interested in the impact of HIV, empiric tuberculosis therapy and fine-needle aspirate for cytology (FNAC) in contributing to delay. RESULTS: Patients (n = 163), 29% HIV-infected, waited a median of 4 weeks before seeking medical attention. It took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention, termed the healthcare practitioner interval. In multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease (OR 2.3, 95% CI 1.1-5.2) and Hodgkin lymphoma (HL) (OR 3.0, 95% CI 1.1-8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3-2.2). The median time to diagnosis was a median of 4 weeks longer for patients on tuberculous (TB) therapy (n = 16, p = 0.28) and patients who underwent an FNAC (n = 63, p = 0.04). Where FNAC was performed, it was diagnostic for lymphoma in only 11%. Diagnostic delay was not associated with overall survival. CONCLUSIONS: Time-to-diagnosis of lymphoma in South Africa was similar to that reported from high-income countries and shows significant periods of delay between the onset of symptoms to diagnosis and treatment. The longest period of delay was in the health practitioner interval. Education regarding the significance of lymphadenopathy for both patients and health care practitioners and appropriate investigative steps preferably by best-practice algorithms specific to TB-endemic areas are needed to shorten the time-to-diagnosis of lymphoma.

Clinical utility of C-terminal telopeptide of type 1 collagen in multiple myeloma.

Myeloma bone disease (MBD) is a major cause of morbidity in multiple myeloma (MM). We investigated bone turnover markers (BTM) as relapse predictors and biomarkers for monitoring MBD. We measured C-terminal telopeptide of type I collagen (CTX-1), and Procollagen type 1 N Propeptide (P1NP) in 86 MM patients and 26 controls. CTX-1 was higher in newly diagnosed patients compared to control, remission and relapse (P < 0·05), and decreased following treatment. In the setting of relapse, a CTX-1 rise greater than the calculated least significant change (LSC) was observed in 26% of patients 3-6 months prior to relapse (P = 0·007), and in 60·8% up to 3 months before relapse (P = 0·015). Statistically significant changes in CTX-1 levels were also observed in patients who were with and without bisphosphonate therapy at the time of relapse. In patients with normal renal function, mean CTX-1 level was highest in the newly diagnosed group (0·771 ± 0·400 µg/l), and lowest in the remission group (0·099 ± 0·070 µg/l) (P < 0·0001). P1NP levels were not statistically different across the patient groups. We conclude that CTX-1, measured on an automated hospital laboratory platform, has a role in routine treatment monitoring and predicting relapse of MBD, even in patients on bisphosphonates.