Multiply relapsing hairy cell leukemia responsive to repeated courses of rituximab: A case report

While cladribine is a highly effective therapy for patients with symptomatic hairy cell leukemia (HCL), up to 37% of patients ultimately relapse and incompletely responding patients relapse more frequently. Rituximab is a monoclonal antibody against CD20 that has been shown to be effective in patients with relapsed HCL. We present an unusual case of successful multiple re-treatments with rituximab in a patient with heavily pre-treated HCL and briefly review the relevant literature.     

An unusual case of autoimmune hemolytic anemia in treatment naïve hepatitis C virus infection

Hepatitis C virus (HCV) infection is emerging as a common and insidiously progressive liver condition. In more than one third of the cases, extrahepatic manifestations are seen in the course of the disease. Over the past decade, authors have reported membranous nephropathy, cutaneous vasculitis, idiopathic thrombocytopenic purpura, porphyria cutanea tarda and diabetes mellitus, among other extrahepatic manifestations of HCV infection. Recently, there have been a growing number of reports relating HCV infection to autoimmune cytopenias. Here, we report an unusual case of Coombs'-negative autoimmune hemolytic anemia (AHA) with severe autoimmune leukopenia and neutropenia, occurring simultaneously, in a patient with untreated hepatitis C infection. Mild cytopenias during chronic hepatitis C have been reported widely in the medical literature; however, severe cytopenias are seldom described and are usually seen only after or simultaneously with therapy.     

Application of flow cytometry in detection of red cell bound IgG in Coombs negative AIHA

Coombs negative autoimmune hemolytic anemia (AIHA) is characterized by laboratory evidence of in vivo hemolysis along with a negative direct antiglobulin test (DAT) performed by conventional tube technique (CTT) in clinically suspected AIHA patients. The sensitive gel test (GT) and flow cytometry (FC) can effectively diagnose such patients where CTT does not detect low level of red cell autoantibodies. We investigated the use of FC in the serological evaluation of CTT DAT negative AIHA and its comparison with GT DAT. Of the 50 patients with suspected AIHA, CTT DAT was negative in 5 patients (Coombs negative AIHA). GT DAT could detect red cell autoantibodies in 4 of these 5 patients. Monospecific GT DAT showed IgG and/or C3d as the responsible autoantibody. FC was considered as reactive when MFI was > 3.6 (mean of 20 healthy negative volunteers +2SD). FC was reactive in all five Coombs negative AIHA patients. The mean MFI in five known CTT DAT positive samples taken for comparison was significantly higher compared to 5 DAT negative AIHA (18.3 ± 7.78 vs. 7.88 ± 1.35, p < 0.05). There was poor correlation between strength of GT DAT and MFI by FC. We conclude that FC is more sensitive test than the CTT and helps in the serological diagnosis of Coombs negative AIHA. However, in resource poor settings, GT DAT can be a good alternative to FC.     

A comparison of conventional tube test and gel technique in evaluation of direct antiglobulin test

In vivo coating of red cells by antibody and/or complement is detected using various sensitive techniques, however most hospitals even today rely on the conventional tube technique (CTT). We compared the performance of the CTT and recently introduced gel test (GT) in the evaluation of direct antiglobulin test (DAT).

The CTT and GT were first compared using in-house prepared control cells. The polyspecific DATs were performed simultaneously by CTT and GT on 170 consecutive blood samples. Positive samples were further tested for monospecific IgG and C3d by both techniques.

GT demonstrated stronger agglutination scores (60 vs. 43) compared to CTT using control cells. The sensitivity and specificity of the GT was 98.4 and 95.2%, respectively as compared to CTT for polyspecific DAT. Discordance between the two test systems was seen in 6/170 patients. Of these, 5 were missed by CTT while GT failed to detect in vivo coating in only 1 case. The agreement between two methods of DAT was 96.4% (κ = 0.926) using polyspecific AHG and 95.7% (κ = 0.379) with mono specific anti-IgG. We conclude that GT is a better alternative to CTT for detecting red cell bound antibodies in various clinical conditions.     

Plasma cell leukemia – a study of 28 cases from India

Abstract

Plasma cell leukemia (PCL) is a rare neoplasm that has not been comprehensively reported in an Indian population. We report the clinico-pathological features of 28 cases studied during 1999–2008. Organomegaly and bleeding tendency was common in primary PCL but not in secondary. Misdiagnosis as acute leukemia or the leukemic phase of lymphoma on the initial peripheral blood smear examination was frequent (31·4% cases) in the primary form of PCL. This is best addressed by an emphasis on the morphological appearances and confirmation by simple serum electrophoresis rather than by more sophisticated testing that may not be widely available. Response to treatment is poor and PCL has a poor prognosis, a situation that may be amenable to improvement by a better understanding of the biology of the disease.     

Evans syndrome: a study of six cases with review of literature

Abstract

Evans syndrome is an uncommon condition characterised by simultaneous or sequential development of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of a known underlying aetiology. The great majority of patients with Evans syndrome have a chronic relapsing course despite treatment, which is associated with significant morbidity and mortality. We reviewed the clinical and laboratory features of six patients with Evans syndrome. All patients had thrombocytopenia, bleeding symptoms and haemolytic anaemia with positive direct Coombs test at presentation. We discuss the aetiopathogenic, clinical, therapeutic and natural history of Evans syndrome.     

Immunoglobulin free light chains: do they have a role in plasma cell leukemia?

Abstract

The assay of serum free light chains (FLCs) is established in the diagnosis and prognosis of several plasma cell dyscrasias, but its significance in plasma cell leukemia (PCL) has not been reported so far. PCL is a rare and aggressive disease with a poor prognosis. The authors describe two cases of PCL with divergent clinical profiles where the serum FLC assay was available. Although both patients had greatly elevated serum β ₂-microglobulin, one patient had much higher levels of serum FLCs and evidence of renal impairment, which were absent in the other; however, the latter, who had multisystem involvement, showed a more rapidly downhill course with early mortality.     

Long-term outcome of ph-negative acute lymphoblastic leukaemia in adults: a single centre experience

BACKGROUND AND OBJECTIVES: In adult acute lymphoblastic leukaemia (ALL), unlike in childhood ALL, the percentage of long-term remitters and survivors has not improved significantly over the last decades. In the present analysis, we describe a series of adult ALL patients consecutively treated with the same regimen in order to analyse prognostic factors and treatment outcome as well as to define new risk-oriented strategies. DESIGN AND METHODS: From 1990 to 1998, 102 newly diagnosed ALL patients were referred to our division, 83 of them were eligible for the present study. Median age was 31 years (range 13-76); 77.1% had B-lineage ALL and 22.9% T-lineage ALL; 36.1% showed associated myeloid markers. All patients received an induction phase treatment, consisting of a 4-week cycle with vincristine, daunorubicin, L-asparaginase and desametasone; the consolidation phase included cyclophosphamide, cytarabine, 6-mercaptopurine and central nervous system (CNS) prophylaxis, followed by three of months maintenance (methotrexate + 6-mercaptopurine), re-induction (4-week cycle with vincristine, adriamicin, desametasone), and 2-year maintenance with methotrexate + 6-mercaptopurine. RESULTS: Complete remission (CR) was achieved in 66 patients (79.5%); 20.5% of patients were resistant. The relapse rate was 60.2%. There were 10 CNS relapses (accounting for 12% of all patients, 15% of all CRs and 20% of all relapses). One patient had an ovarian and 2 had a breast relapse. Eleven patients remained in first continuous CR after chemotherapy. Median overall survival (OS) and disease-free survival (DFS) were 1.8 and 1.0 years, respectively, with a median follow-up of 5.6 years (range 0.3-12.1). Initial white blood cell count 相似文献   

Complete resolution of hepatic aspergillosis after non-myeloablative hematopoietic stem cell transplantation in a patient with acute myeloid leukemia

Fungal infections due to Aspergillus are a frequent cause of transplant-related mortality. For this reason, leukemic patients with severe fungal infection are usually excluded from conventional allotransplantation. Recently, some authors suggested a role for non-myeloablative hematopoietic stem cell transplantation (HSCT) in this subset of patients. We used this therapeutic approach in a patient with high-risk acute myeloid leukemia in second complete remission (CR) with pre-existing hepatic aspergillosis refractory to conventional anti-fungal therapy. A complete regression of hepatic lesions was observed after 3 months from allogeneic stem cell transplantation. Our work confirms previous reports suggesting that non-myeloablative HSCT is effective in patients not eligible for conventional transplantation because of invasive aspergillosis.     

High density genome-wide DNA profiling reveals a remarkably stable profile in hairy cell leukaemia

Hairy cell leukaemia (HCL) is a rare B-cell neoplasm for which the molecular mechanisms are largely unknown. High-density genome-wide DNA profiling was performed with Affymetrix 250K arrays to analyse copy number (CN) changes and loss of heterozygosity (LOH) in 16 cases of HCL. Four of 16 cases (25%) demonstrated gross non-recurrent CN deletions. Within the affected regions, we identified genes involved in bone marrow fibrosis (FGF12) and response to treatment (TP53) in individual cases. Large regions (> 5 Mb) of LOH without any concomitant DNA CN changes were identified in 5/16 (31%) HCL and were indicative of uniparental disomy UD. The germline origin of UD was demonstrated in one case for which a matched normal sample was available. Overall analysis of LOH showed that identical loci were recurrently targeted in chromosomes 1, 2 and 6. As a whole, however, HCL showed a remarkably stable genome. This finding adds to several other features that are unique to HCL among mature B-cell tumours.     

Osteopetrosis: a single centre experience of stem cell tranisplantation and prenatal diagnosis

Malignant osteopetrosis (MOP) is an autosomal recessive disease in which osteoclast dysfunction results in excessive bone deposition and early infant death. Thirteen children suffering from MOP from four related families all belonging to one Bedouin tribe, were studied. The disease was diagnosed as early as at a few days postnatal to 5 months. Nine children underwent BMT, four of whom are still alive; one is blind and two have markedly reduced vision. Four children who did not undergo BMT died between 4 and 6 months of age. Recently, the gene for MOP has been mapped for this Bedouin tribe allowing prenatal diagnosis. Seven pregnancies were subsequently prenatally diagnosed and two fetuses were found to be affected. Pregnancy was electively terminated in one case. In the other case the parents refused and after establishing the diagnosis, the newborn was transplanted at the age of 7 days.     

Thirty-nine cases of pure red cell aplasia: A single center experience from India

Pure red cell aplasia (PRCA) is an uncommon disorder, characterized by transfusion dependent anemia, reticulocytopenia with selective aplasia or paucity of erythroid cells in bone marrow. There are only a few large series of PRCA reported in literature. This is the largest single center series of PRCA from India.

Objective: To evaluate the utility of Immunohistochemistty with Glycophorin A on bone marrow biopsies in quantitating the cut-off percentage of erythroid blasts required for diagnosis, as the upper cut-off percentage of erythroblasts for establishing a diagnosis of PRCA is still not clear.

Methods: The clinical data were obtained from patients' case files. Immunohistochemistry with Glycophorin A was performed using an immunoperoxidase technique and percentage of Glycophorin A positive cells of all nucleated cells was calculated by two independent observers.

Results: In our study, bone marrow aspirates showed a variable percentage of erythroblasts ranging from 2 to 12% (mean 6.3%) in children and from 1 to 8% (mean 4.6%) in adults on Giemsa smears. Immunohistochemistry (IHC) with Glycophorin A showed a mean positive cell % of 8.2 (range 2–16%) and 6.8 (1–9%) in pediatric and adult respectively against a mean of 28% (range 21–39%) in idiopathic thrombocytopenia (ITP) cases. Treatment with prednisone showed good response in a majority of both adults and childhood PRCA. Cyclosporine was found to be a good alternative in prednisone non-responders. Thymectomy was beneficial in patients with thymoma.

Conclusion: A higher percentage of erythroid cells (>5%) does not exclude a diagnosis of PRCA in an appropriate clinical setting and therefore can be managed as PRCA.     

Allogeneic bone marrow transplantation for juvenile myelomonocytic leukaemia: a single centre experience and review of the literature

Juvenile myelomonocytic leukaemia (JMML) is a rare paediatric disease and allogeneic stem cell transplantation is the only curative approach. The roles of pretransplant treatment, conditioning regimen and graft-versus-host disease (GVHD) are still unclear. Eleven children with JMML underwent allogeneic BMT in our institution. Donors were matched unrelated (n = 6) matched siblings (n = 4) and one mismatch family donor. Transplant-related mortality (TRM) was 36%. Three patients relapsed after transplantation. Two of three patients with relapse are in continuous remission after donor lymphocyte infusion or second BMT, respectively. To evaluate the role of pretransplant treatment, conditioning regimen and GVHD, we have summarised our series with other published single centre reports and give an overview on a total of 65 patients with JMML who underwent allogeneic BMT. No significant correlation between pretransplant treatment, conditioning regimen and TRM could be observed. Overall relapse rate is high (47%). TBI is associated with a significantly higher relapse rate (P = 0.012). Other conditioning modalities, intensive chemotherapy and splenectomy prior to stem cell transplantation do not seem to have a significant impact on relapse rate. Patients with or without GVHD showed no significant difference in relapse rate (58% vs 45%). In the event of relapse after transplantation withdrawal of immunosuppression, donor lymphocyte infusion or second transplant was successful in 6/11 patients. Graft-versus-leukaemia effect seems to play an essential role in bone marrow transplantation for JMML.     

Evidence of graft-versus-Waldenstrom's macroglobulinaemia effect after allogeneic stem cell transplantation: a single centre experience

The role of allogeneic stem cell transplantation (SCT) in Waldenstrom's macroglobulinaemia (WM) is not yet clear, as published data on allogeneic SCT in WM are limited. We present a retrospective study of allogeneic SCT in five patients with WM. Median age was 56 years (range 40-60 years). All patients were heavily pretreated. Conditioning therapy with busulphan and cyclophosphamide was used for all patients and all were given cyclosporine and methotrexate for graft-versus-host disease prophylaxis. With a median follow-up of 32 months (range 2-43), all except one are alive and disease free. Progressive, delayed decline in serum IgM levels were noted in all the patients, suggesting an active graft-versus-Waldenstrom's effect. With the limited available data, it appears that allogeneic SCT is a useful treatment option for advanced WM.     

Peripheral blood stem cell collection in 24 low-weight infants: experience of a single centre

Peripheral blood stem cells (PBSC) harvest may be difficult in young children. Extracorporeal separator line priming by red blood cells is usually required to improve haemodynamic tolerance and efficacy of collection. We present our experience with 24 children weighing less than 15 kg treated between January 1997 and September 1999, in whom we tried to avoid systematic blood priming. The median age and weight at the time of apheresis were 2.4 years and 12 kg, respectively. A total of 48 PBSC were performed. When haemoglobin was less than 12 g/dl, packed red cells were transfused before collection (40% of aphereses). The median cell yield per apheresis was 7.1 (2.2-30.6)x10(6)/kg CD34(+) cells and 16.0 (3.3-44.3)x10(5) CFU-GM/kg. Initial collection failed in three cases. Four children required an additional haematopoietic progenitor mobilization. This procedure allowed PBSC collection without transfusion in 37.5% of children, and was safe (two serious and five mild transient side effects) and effective (median CD34(+) cells collected per child: 7.1 x 10(6)/kg (4.6-30.6) and CFU-GM: 15.1 x 10(5)/kg (4.7-44.3)). Despite their low weight, insertion of a femoral catheter was avoided in 43% of children.     

Kasabach–Merritt phenomenon: a single centre experience

Objective: Kasabach–Merritt phenomenon (KMP) can lead to life‐threatening bleeding, and its optimum treatment has not been established. We review the experience of managing KMP in a single institution. Methods: A retrospective chart review on all children with KMP treated at the Hospital for Sick Children, Toronto, over an 18 yr period was carried out. Results: All 15 patients had profound thrombocytopenia and hypofibrinogenemia at presentation, half had bleeding symptoms, and three had cardiac failure. All patients received corticosteroids. Five responded to steroids alone, given for an average of 13 wk, increasing platelets to >20 × 10⁹/L at a mean of 6.2 d and fibrinogen >1 g/dL at 25.6 d. Ten patients received at least one other therapeutic modality in addition to steroids, including vincristine, interferon, anti‐platelet agents and pentoxifylline. Five patients received vincristine, for a mean of 6 wk, with two patients responding. Eight patients received interferon, for a mean of 4 months, with two patients responding. Overall, the mean time to increasing platelets >20 × 10⁹/L was 56 d, to >150 × 10⁹/L was 88 d and fibrinogen >1 g/dL 49 d. Ten patients showed a partial response to embolisation, with a mean of 2.8 procedures performed. Thrombotic complications occurred in 7%. Twelve patients remain alive, with relapse in six patients, all treated successfully. One patient died, and two patients have been lost to follow‐up. Conclusion: KMP is a rare condition, with significant morbidity and mortality. The therapeutic approach should include a multidisciplinary team and consensus on guidelines.