Trapeziectomy and suspension arthroplasty with the flexor carpi radialis tendon for treatment of trapeziometacarpal osteoarthritis.

Excision of the trapezium is the common step in most arthroplasties for treating trapeziometacarpal arthritis. Trapeziectomy can be supplemented by several techniques intended to stabilize the first metacarpal but none of these has been proven superior. The aim of this study was to verify if a simplified suspension arthroplasty with the flexor carpi radialis (FCR) tendon, requiring only a single short surgical incision, no intraosseous tunnels and no interposition of prosthetic material, yields equal clinical outcomes to more complex techniques and if the clinical outcomes remain stable over the long term. A cohort of 299 patients was reviewed retrospectively at a follow-up ranging from 3 to 12 years (mean follow-up time 6 years) following total trapeziectomy and suspension arthroplasty using a half-tendon strip of FCR. At this long-term follow-up, the mean DASH score improved from 52 preoperatively to 20 postoperatively. Pain at follow-up was subjectively rated by patients as absent or improved in 92% cases. Thumb opposition assessed on the Kapandji scale was rated 9 or 10 in 144 (76%) hands, 7 or 8 in 30 (16%) hands and <7 in 15 hands (8%). Mean palmar flexion and radial abduction were 45° and 42°, respectively. Mean key pinch and grip strength were 4.7 Kg and 23.5 kg, respectively. When treating trapeziometacarpal osteoarthritis, surgical techniques that do not require complex procedures, bone tunnels, K wire stabilization or interposition of prosthetic materials can be considered and maybe preferred. Our technique of trapeziectomy and suspension arthroplasty with the FCR tendon produces good long-term results.

Morphologic and immunophenotypic features of a case of acute monoblastic leukemia with unusual positivity for Glycophorin-A.

Acute monoblastic leukemia (AMoL) is characterized by cells with highly undifferentiated morphology. Cytochemistry with non-specific esterases is negative in up to 20% of cases. Immunophenotyping by flow cytometry has an essential role in diagnosing such a subtype of leukemia and a multiparametric approach with a wide monoclonal antibody panel is necessary. We describe a case of AMoL with morphology resembling either plasma blasts or very immature erythroblasts. Diagnosis was made by alpha-naphtyl-acetate esterase staining and with immunophenotyping, which was made with a wide monoclonal antibody panel. Blasts were positive for monocytic markers. Most of leukemic cells, however, were positive for Glycophorin-A. The presence of Glycophorin-A, which is considered as a specific marker of the erythroid lineage, has never been reported previously in cases of AMoL. This peculiar immunophenotype might be interpreted as deriving from a common myelo-erythroid precursor undergone leukemic transformation.

Modifications in B-Lymphocyte Number and Phenotype in the Course of Pregnancy in a Woman with Persistent Polyclonal B-Cell Lymphocytosis: A Flow Cytometric Study.

Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare clinical condition, characterized by a persistent, generally moderate lymphocytosis, generally due to stimulation of central memory B-lymphocytes, and by a moderate increase of polyclonal IgM. In some patients, slight or moderate splenomegaly is observed. A variable percentage of circulating, bone marrow and splenic lymphocytes display an abnormal nucleus (generally bilobated) or are binucleated. The clinical course is benign in most cases and transformation into splenic B-cell lymphoma occurs in few cases. In the current paper we report the first case of pregnancy in PPBL. Our patient became pregnant 18 months after diagnosis. In the course of pregnancy, a marked down-regulation of lymphocytosis (from 6 × 10(9)/L to 2.1 × 10(9)/L) and a decrease in B-lymphocyte number was observed (from 3.6 × 10(9)/L to 1 × 10(9)/L), mainly due to a marked reduction in the percentage and absolute number of central memory B-cells. Such modifications were similar to those described in normal pregnant women. One year after the delivery of a healthy female baby, the number of total lymphocytes and B-lymphocytes showed an inverse behavior, with a new expansion of central memory B-cells. Our case shows that a normal pregnancy can occur in patients with PPBL and that pregnancy can induce marked modifications in B-lymphocyte kinetics and phenotype.

Myelomatous meningitis evaluated by multiparameter flow cytometry : report of a case and review of the literature.

Central nervous system (CNS) involvement in multiple myeloma (MM) is uncommon. Among its possible presentations, leptomeningeal involvement of MM, also termed central nervous system myelomatosis (CNS-MM) is rare and is characterized by the presence of neoplastic plasma cells in the cerebrospinal fluid (CSF). So far, 187 cases of CNS-MM have been reported : the great majority of them were diagnosed by cytological assays and flow cytometry was used in only eight cases. We describe a case of CNS-MM in a 62-year-old woman, previously treated with chemotherapy (VTD) and autologous peripheral blood hematopoietic stem cell transplantation for stage IIIB IgG-λ MM. After achieving a very good partial response, the patient showed progression of disease, with an extramedullary localization. During administration of second-line therapy, the patient showed severe neurological symptoms. MRI resulted negative. Diagnosis of CNS-MM was made by multiparameter flow cytometry, which showed the presence of CD56(+) plasma cells in a CSF sample, in the absence of plasma cell leukemia. In this paper we also present a review of the eight previous cases of CNS-MM diagnosed by flow cytometry. We found that the application of flow cytometry in cases of MM with neurological symptoms allows a rapid diagnosis of CNS-MM and provides useful information about plasma cell phenotype (including CD56 expression). Some cases of CNS-MM are characterized by normal MRI. In addition, some evidences deriving from the review of literature suggest that CSF monitoring by flow cytometry in such cases might be used to evaluate the efficacy of drugs capable of crossing the blood-brain barrier.

Multiparameter Flow Cytometry to Detect Hematogones and to Assess B-lymphocyte clonality in Bone Marrow Samples from Patients with Non-Hodgkin Lymphomas.

Hematogones are precursors of B-lymphocytes detected in small numbers in the bone marrow. Flow cytometry is the most useful tool to identify hematogones and, so far, 4-color methods have been published. In addition, flow cytometry is used in the diagnosis and follow-up of lymphomas. We developed a flow cytometric 7-color method to enumerate hematogones and to assess B-lymphocyte clonality for routine purposes. We evaluated 171 cases of B-cell non-Hodgkin lymphomas, either at diagnosis or in the course of follow-up. By our diagnostic method, which was carried out by the combination K/λ/CD20/CD19/CD10/CD45/CD5, we were able to detect hematogones in 97.6% of samples and to distinguish normal B-lymphocytes, neoplastic lymphocytes and hematogones in a single step. The percentage of hematogones showed a significant inverse correlation with the degree of neoplastic infiltration and, when bone marrow samples not involved by disease were taken into consideration, resulted higher in patients during follow-up than in patients evaluated at diagnosis.

Simultaneous presentation of Waldenström macroglobulinemia and multiple myeloma: multidisciplinary diagnosis, treatment and 30-month follow-up.

Waldenström macroglobulinemia and multiple myeloma are mature B-cell neoplasms deriving from post-germinal cells at different stages of differentiation. The simultaneous presentation of Waldenström macroglobulinemia and multiple myeloma in the same patient is a very rare phenomenon and, so far, only two cases have been described. We report the case of a 75-year Caucasian female patient, with a silent clinical history, who presented with anemia and two different monoclonal proteins (IgMκ and IgGκ). The trephine biopsy showed the presence of a dual population, represented by small lymphoplasmacytoid cells and by plasma cells, which infiltrated the bone marrow with a clearly different pattern. Both immunohistochemistry and flow cytometry demonstrated the biclonal origin such neoplastic cells, since lymphoplasmacytoid cells resulted IgMκ while plasma cells were IgGκ. This biclonal pattern was further confirmed by the demonstration of a different IgH gene rearrangement of the two neoplasms. The patient was treated with bortezomib, dexamethasone and rituximab, achieving partial remission of both Waldenström macroglobulinemia and multiple myeloma. After a 30-month follow-up, she is in stable disease. Multiple myeloma has been described in association with other indolent B-cell neoplasms, mostly chronic lymphocytic leukemia, while Waldenström macroglobulinemia can be followed by diffuse large B-cell lymphoma in some instances, after chemotherapy. The association of Waldenström macroglobulinemia and multiple myeloma seems to be very rare. Our study shows that an integrated diagnostic work-up is very useful in such cases, with an interesting role for flow cytometry. [J Clin Exp Hematop 53(1): 29-36, 2013].

B-cell acute lymphoblastic leukemia with t(4;11)(q21;q23) in a young woman: evolution into mixed phenotype acute leukemia with additional chromosomal aberrations in the course of therapy.

About 5% of adult B-cell acute lymphoblastic leukemias (B-ALL) are characterized by t(4;11)(q21;q23), which confers peculiar features to this B-ALL subtype, including a very immature immunophenotype and poor prognosis. We describe the case of a 21-year-old female who presented with B-ALL carrying the t(4;11)(q21;q23) and blasts positive for CD19, TdT, CD79a, CD38, HLA-DR. Before completing the Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) therapy regimen, the B-cell leukemic clone still was detected, but an additional leukemic clone appeared, with morphology and immunophenotype (CD13, CD33, CD64, CD38, CD56, CD15, CD4(dim)) compatible with derivation from the myeloid/monocytic lineage. Karyotype showed the co-existence of three cell lines, with persistence of t(4;11)(q21;q23) and appearance of +8,+12,+13 and two der(4). The patient died because of disseminated intravascular coagulation. Our report describes a rare, possible evolution of such a subtype of B-ALL, with transformation into mixed phenotype acute leukemia in the course of therapy. This finding suggests a blast cell derivation from a common lymphoid/monocytic precursor leading to a final bilineal acute leukemia.

The role of CD19 and CD27 in the diagnosis of multiple myeloma by flow cytometry: a new statistical model.

We have developed a new statistical diagnostic model that examines the correlation between immunophenotype and clonality as detected by flow cytometry (FC) and histology, defining the diagnostic role of FC in multiple myeloma (MM). The 192 bone marrow samples from patients and control subjects were studied for routine diagnostic analysis of MM; a minimum of 100 plasma cells (PCs) were analyzed for each patient sample. A direct 7- or 8-color method was applied to study the immunophenotype of PCs, utilizing a FACSCanto II (BD Biosciences, San Jose, CA). Samples were labeled with fluorochrome-conjugated monoclonal antibodies (AmCyan, Pac Blue, fluorescein isothiocyanate, phycoerythrin [PE], PECy7, peridinin-chlorophyll protein, allophycocyanin [APC], and APC-Cy7) to the following antigens: CD138, CD81, CD200, CD221, CD45, CD38, CD28, CD19, CD27, CD117, CD38, CD33, CD20, CD56, CD10, and immunoglobulin κ and λ light chains. Among all antigens tested, CD19 and CD27, when applied to our model, resulted in optimal concordance with histology. This model defines the effective diagnostic role FC could have in MM and in the detection of minimal residual disease.

Lithium in the treatment of neutropenia.

PURPOSE OF REVIEW: The capacity of lithium to induce neutrophilia and increase circulating CD34(+) cells of marrow origin has long been known. Lithium has been the object of hematological investigations for many years, but no definitive use in hematology has yet emerged. RECENT FINDINGS: We review the evidence that lithium increases granulocyte colony-stimulating factor (G-CSF) and augments G-CSF effects, showing its potential use in stem cell mobilization and engraftment of stem cell transplantation. SUMMARY: We suggest possible therapeutic uses of lithium in neutropenia. In bone marrow transplantation, preharvest lithium-assisted hematopoietic stem cell mobilization may be useful as well.

High-dose (40,000 IU twice/week) alpha recombinant human erythropoietin as single agent in low/intermediate risk myelodysplastic syndromes: a retrospective investigation on 133 patients treated in a single institution.

We investigated the efficacy of alpha recombinant human erythropoietin (α-rHuEPO) administered as single agent to 133 patients affected by myelodysplastic syndromes referring to our Institution in the last 10 years. WPSS score was "very low" in 67%, "low" in 19%, "intermediate" in 14%. The starting schedule was: 40,000 IU bi-weekly, with reduction or suspension, when necessary, in responsive patients. According to new IWG criteria, response rate (RR) was 75%, 66%, 59% after 8, 16, 24 weeks, respectively. Comparing "very low" and "low/intermediate" risk, RR was 81% vs. 43% (P < 0.001); 70% vs. 45% (P = 0.040); 63% vs. 42% (P = NS) after 8, 16, 24 weeks. RR was significantly influenced by transfusion dependence (P = 0.039) and basal serum EPO level (P < 0.001). Mean Hb value was 94 ± 11 g/l before therapy; 114 ± 19 after 8 weeks (P < 0.001); 116 ± 18 after 16 weeks (P < 0.001); 114 ± 17 after 24 weeks (P < 0.001). Reduction or suspension of therapy significantly affected Hb level after 4 (P < 0.001) and 8 weeks (P < 0.01). Conversely, restart of full dosage significantly enhanced again Hb level after 4 (P < 0.01) and 8 weeks (P < 0.001). 65% patients are alive (mean survival: 74 weeks). Seventy percent are alive in the "very low risk" group and 38% in "low/intermediate risk" group (P < 0.001). Overall mean follow-up was 69 weeks (range, 8-376): it was 80 weeks in responsive patients (max 376) and 38 weeks in patients who progressively became unresponsive (max 168) (P < 0.01). Median response was 36 weeks, with 33% of patients still responding after one year. Treatment was well tolerated.

Prethymic cytoplasmic CD3 negative acute lymphoblastic leukemia or acute undifferentiated leukemia: a case report.

Acute undiffentiated leukemia (AUL) is an acute leukemia with no more than one membrane marker of any given lineage. Blasts often express HLA-DR, CD34, and/or CD38 and may be positive for terminal deoxynucleotidyl transferase (TdT). The expression of CD34, HLA-DR, and CD38 has been shown in pro-T-ALL, although in this case, blasts should also express CD7 and cyCD3. However, some cases of T-ALL without CD3 in the cytoplasm and all TCR chain genes in germ line configuration are reported, features that fit well with a very early hematopoietic cell. We report a case of acute leukemia CD34+/-HLADR+CD7+CD38+cyCD3- in which a diagnosis of AUL was considered. However the blasts were also positive for CD99 and TCR delta gene rearrangement which was found on molecular studies. Therefore a differential diagnosis between AUL and an early cyCD3 negative T-ALL was debated.

Glycosylation interference on RhoA activation: focus on G-CSF.

Glycosylation of cytokines appears to be responsible for several differences in their activity, and focusing on G-CSF, several divergences between the non-glycosylated G-CSF, Filgrastim, and the glycosylated G-CSF, Lenograstim, have been reported. To verify the role of G-CSF glycosylation in mediating these differences we tested in vitro the effects on the RhoA activation of the different G-CSFs, including deglycosylated Lenograstim. The results showed that Filgrastim induced sustained-RhoA activation while Lenograstim did not do so. Deglycosylated Lenograstim mimicked Filgrastim, resulting in RhoA hyper-activation. These in vitro findings demonstrate that the glycosylation of G-CSF plays a crucial role in RhoA activation.

Meningeal relapse in a case of B acute lymphoblastic leukemia: the role of CD56 expression.

BACKGROUND: Blasts from B acute lymphoblastic leukemia (B-ALL) may express CD56 in about 10% of cases. The presence of this marker at diagnosis is associated with an increased risk of meningeal relapse. A case is described of B-ALL which was CD56 negative at diagnosis, and expressed this marker when isolated meningeal relapse was diagnosed. CASE REPORT: A 53-year-old female patient presented with neurological symptoms during maintenance therapy for B-ALL. Peripheral blood, bone marrow, and cerebrospinal fluid (CSF) were subjected to both morphological and flow cytometric analyses. The latter was carried out by a wide routine panel of MoAbs which was the same as the one at diagnosis and included CD56. Isolated meningeal relapse was diagnosed since blast cell infiltration was detected in the CSF, but not in the peripheral blood and bone marrow samples. Blast cells showed an immunological phenotype similar to that at diagnosis (cyCD79a+, CD79b+, CD19+, CD22+, CD34+, CD10+, CD20+), but characterized by the acquisition of CD56 on the surfaces of more than 90% of cells. CONCLUSIONS: This case shows that CD56 can be expressed at relapse of B-ALL and that its presence likely enables leukemic cell binding to the central nervous system (CNS). This phenomenon may be responsible for the isolated CNS relapse diagnosed in this patient.

Lithium and hematology: established and proposed uses.

Lithium (as lithium carbonate) is an inexpensive drug, widely used in psychiatry for over 50 years in treatment of mood instability (bipolar disorder) and as an adjunct to antidepressants. Hematological effects of neutrophilia and increased circulating CD34+ cells of marrow origin have long been known. Lithium was at the center of hematological investigations in the 1980s, but no definitive use in hematology has yet emerged. We review evidence that lithium increases G-CSF and augments G-CSF effects. We suggest possible therapeutic uses of lithium in neutropenia. In bone marrow transplantation, preharvest lithium-assisted hematopoietic stem cell mobilization may be useful as well.