Induction with oral chemotherapy (CID) followed by early autologous stem cell transplantation for de novo multiple myeloma patients.

In an effort to minimise induction therapy-related toxicity, avoid unnecessary hospitalisation and facilitate early ASCT, we have prospectively evaluated an outpatient-based oral chemotherapeutic regimen, cyclophosphamide, idarubicin, dexamethasone (CID) in patients with previously untreated multiple myeloma (mm). Patients subsequently underwent ASCT conditioned with melphalan 200 g/m(2). A total of 36 newly diagnosed MM patients were enrolled between February 1997 and March 2000. In all 136 cycles of CID were administered requiring only four unplanned hospital admissions. Grade 3 or 4 haematological toxicities were documented following 14 cycles (10%). There were no treatment-related deaths. Response rates (PR + CR) based on an intention-to-treat basis were 66% (23 of 35, 9% CR) post-CID and 80% (28 of 35, 34% CR) post-ASCT. In all, 28 of the 35 patients remain alive with a median follow-up for surviving patients of 40 months (range, 30-67 months). Progression-free survival from the time of diagnosis was 32 months (range, 3-55+ months). Median overall survival from diagnosis has not been reached with an estimated overall survival at 4 years of 77%. CID in combination with early ASCT is an effective and well-tolerated antimyelomatous regimen and is a practical alternative to more toxic and invasive therapeutic approaches.

Practical considerations for the measurement of free light chains in serum.

BACKGROUND: A new immunoassay for free light chain measurements has been reported to be useful for the diagnosis and monitoring of monoclonal light chain diseases and nonsecretory myeloma. We describe experience with and some potential pitfalls of the assay. METHODS: The assay was assessed for precision, sample type and stability, recovery, and harmonization of results between two analyzers on which the reagents are used. Free-light-chain concentrations were measured in healthy individuals (to determine biological variation), patients with monoclonal gammopathy of undetermined significance, myeloma patients after autologous stem cell transplants, and patients with renal disease. RESULTS: Analytical imprecision (CV) was 6-11% for kappa and lambda free-light-chain measurement and 16% for the calculated kappa/lambda ratio. Biological variation was generally insignificant compared with analytical variation. Despite the same reagent source, values were not completely harmonized between assay systems and may produce discordant free-light-chain ratios. In some patients with clinically stable myeloma, or post transplantation, or with monoclonal gammopathy of undetermined significance, free-light-chain concentration and ratio were within the population reference interval despite the presence of monoclonal intact immunoglobulin in serum. In other patients with monoclonal gammopathy of undetermined significance, values were abnormal although there was no clinical evidence of progression to multiple myeloma. CONCLUSIONS: The use of free-light-chain measurements alone cannot differentiate some groups of patients with monoclonal gammopathy from healthy individuals. As with the introduction of any new test, it is essential that more scientific data about use of this assay in different subject groups are available so that results can be interpreted with clinical certainty.

A single-centre experience of post-renal transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) complicates 1 to 10% of all transplantations. Previous clinicopathological studies of PTLD have been limited by small numbers, short follow-up times, outdated data, heterogeneity of pooled solid-organ transplant results, and selective inclusion of early-onset disease. We therefore undertake here a retrospective analysis and identify all cases of PTLD that complicated renal transplantation at the Princess Alexandra Hospital between 30 June 1969 and 31 May 2001. Tumour samples were subsequently retrieved for pathological review and for Epstein-Barr virus-encoded RNA in situ hybridisation (EBER-ISH). Of 2,030 renal transplantation patients, 29 (1.4%) developed PTLD after a median period of 0.5 years (range 0.1 to 23.3 years). PTLD patients were more likely to have received cyclosporine (76% versus 62%, P<0.05), tacrolimus (10% versus 2%, P<0.05) and OKT3 (28% versus 10%, P<0.01). As the burden of immunosuppression increased from dual, to triple, to OKT3 therapy, the risks of early onset, extensive-stage, polymorphic, Epstein-Barr virus (EBV)-associated and fatal PTLD progressively increased. The majority of patients presented with an extra-nodal mass (45%), were afebrile (76%), and had stage-IV disease (60%). EBER-ISH was positive in 58%. Actuarial 5-year disease-free survival was 53.7%. The independent predictors of mortality on multivariate Cox regression were polymorphic histology (HR 7.4, 95% CI 1.5-37) and an international prognostic index (IPI) >1 (HR 2.7, 95% CI 1.1-6.8). Compared with other treatments, chemotherapy was associated with higher survival rates (100% versus 18% at 3 years, P=0.0001). In conclusion, PTLD is more likely, occurs earlier, and is more often fatal, in the setting of intensive immunosuppression. Nevertheless, excellent long-term outcomes are achievable with early recognition and institution of appropriate treatment.

Incidence and nature of CD20-negative relapses following rituximab therapy in aggressive B-cell non-Hodgkin's lymphoma: a retrospective review.

Re-treatment with rituximab for B-cell non-Hodgkin's lymphoma (NHL) relapsing after previous rituximab therapy has recently been shown to be clinically efficacious. Although the mechanism of resistance to rituximab re-treatment in non-responding patients is unknown, it is possible that loss of CD20 expression in the relapsed NHL could be important in some patients. We examined the incidence and nature of CD20 negative relapses following rituximab therapy in aggressive B-cell NHL treated at our institution. Of a total of 18 patients who received rituximab, 13 have relapsed, with 10 patients subsequently undergoing repeat tissue biopsy. Six of these 10 patients (60%) were shown to have lost CD20 expression by either immunohistochemistry and/or flow cytometry. Furthermore, three of the six patients who relapsed with CD20-negative NHL also suffered relapses at unusual anatomical sites. We conclude that loss of CD20 expression in aggressive B-cell NHL relapsing post-rituximab therapy is common. As such, repeat tissue biopsy should be undertaken to document CD20 expression by both flow cytometry and immunohistochemistry prior to considering repeated courses of rituximab in relapsed aggressive lymphomas.

Neutrophil dysplasia characterised by a pseudo-Pelger-Huet anomaly occurring with the use of mycophenolate mofetil and ganciclovir following renal transplantation: a report of five cases.

AIM: The pseudo-Pelger-Huet (PH) anomaly has been associated with a variety of primary haematological disorders, infections and drugs. Recently, the development of dysgranulopoiesis characterised by a pseudo-PH anomaly has been reported in two patients with the use of mycophenolate mofetil (MMF) in the setting of heart and/or lung transplantation. We present a further five cases of MMF-related dysgranulopoiesis characterised by a pseudo-PH anomaly occurring after renal transplantation. METHODS: All patients were receiving standard immunosuppression protocols for renal transplantation, including a combination of MMF, steroids and either cyclosporin or tacrolimus. Oral ganciclovir was also used for cytomegalovirus prophylaxis in each case. RESULTS: Development of dysplastic granulopoiesis occurred a median of 96 days (range 66-196 days) after transplantation. Moderate or severe neutropaenia (<1.0 x 10(9)/l) developed in three cases, and appeared to be directly correlated with the percentage of circulating neutrophils present with dysplastic morphology. Resolution of dysgranulopoiesis occurred in all cases only after dose reduction and/ or cessation of both MMF and ganciclovir. CONCLUSIONS: In our series, the observed dysplastic granulopoiesis appeared related to the combination of MMF and ganciclovir, rather than MMF alone. Further study is required to determine the exact incidence and pathogenesis of this pattern of bone marrow toxicity.

Identification of tumours with the CD43 only phenotype during the investigation of suspected lymphoma: a heterogeneous group not necessarily of T cell origin.

AIMS: CD43 is usually employed as a T cell marker in the immunophenotypic work-up of suspected cases of non-Hodgkin's lymphoma (NHL). In this setting, tumours expressing CD43 in the absence of other T or B cell markers (CD43 only phenotype) are rare. We present four cases with this aberrant phenotype seen at our institution. METHODS: The CD43 only phenotype was defined as expression of CD43 in the absence of expression of B cell markers CD20 and CD79a, and T cell markers CD3 and CD5, on initial immunohistochemistry performed on biopsies of suspected NHL. Combinations of further immunohistochemistry, flow cytometry, cytogenetic analysis and molecular studies were used to enable further diagnosis and lineage assignment. RESULTS: The four cases were subsequently diagnosed as: one case of extramedullary acute myeloid leukaemia, one case of null cell anaplastic large-cell lymphoma, and two cases of extranodal diffuse large B cell lymphoma. None were demonstrated to be of T cell origin. CONCLUSIONS: Our series further confirms the lack of specificity of CD43 expression for T cell lineage. Documentation of the CD43 only phenotype in suspected cases of NHL therefore requires further investigation to both correctly diagnose and clarify lineage of these tumours.