Pregnancy complications predict thrombotic events in young women with essential thrombocythemia

Although Philadelphia‐negative myeloproliferative neoplasms (MPNs) occur typically in middle to advanced age, any age group may be affected, posing a challenge for their management during pregnancy when they occur in young females. There is a high incidence of thromboembolic events and pregnancy complications in patients with myeloproliferative neoplasms, and a possible relationship between these complications is a matter of concern. The aim of this article was to correlate thrombosis and pregnancy outcome in 158 females with ET experiencing 237 pregnancies. Seven patients had a thrombotic event before their first pregnancy, one of them ended (14.3%) in a miscarriage. Among the 151 patients with no history of thrombosis before they became pregnant, 40 (26.5%) had a miscarriage (P = NS). Eighteen patients (11.4%) developed major thrombotic complications (12 splanchnic vein, 1 cerebral vein, 2 coronary syndromes, and 3 strokes) after at least one pregnancy (4 uneventful and 14 complicated). The occurrence of thrombosis was significantly more frequent (P < 0.001) in patients with a history of pregnancy complications (28%) than in those experiencing a normal pregnancy and delivery (3.7%). Pregnancy complications in women with ET are associated with a higher risk of subsequent thromboses, so pregnant women with this neoplasm who miscarry need to be carefully monitored. Am. J. Hematol. 89:306–309, 2014. © 2013 Wiley Periodicals, Inc.     

Adoptive immunotherapy for cancer

Recent clinical success has underscored the potential for immunotherapy based on the adoptive cell transfer (ACT) of engineered T lymphocytes to mediate dramatic, potent, and durable clinical responses. This success has led to the broader evaluation of engineered T-lymphocyte-based adoptive cell therapy to treat a broad range of malignancies. In this review, we summarize concepts, successes, and challenges for the broader development of this promising field, focusing principally on lessons gleaned from immunological principles and clinical thought. We present ACT in the context of integrating T-cell and tumor biology and the broader systemic immune response.     

The aging effect of chemotherapy on cultured human mesenchymal stem cells

Various agents, including chemotherapeutic drugs, can induce cell senescence. However, the mechanisms involved in the aging pathway, particularly the stress that chemotherapy imposes on telomeres, are still undefined. To address these issues, human mesenchymal stem cells (MSCs) were assessed as target cells to investigate the initiation of the aging process by chemotherapy. The MSCs were obtained from bone marrow (BM) cells from normal adults and grown in the presence of platelet lysates. Cultured MSCs were identified for immunophenotype, and for growth and differentiation properties. The MSCs were exposed to 10 nM doxorubicin and 500 ng/mL etoposide, sublethal doses that induce DNA double-stranded breaks. Telomere length (TL) was assessed by flow-fluorescence in situ hybridization and Southern blotting. Initial TL shortening was detectable in MSCs at 5 days after drug exposure, with progressive reduction compared with untreated cells at 7, 14, 21, and 28 days in culture. After a single exposure, MSCs were unable to regain the lost telomere sequences for up to 28 days in culture. The ATM phosphorylation was documented early after drug exposure, while no telomerase activation was observed. Chemotherapy-induced TL shortening was associated with reduced clonogenic activity in?vitro and accelerated adipose differentiation. Analogous behavior in the differentiation pattern was observed in naturally aged MSCs. These results indicate that cultured MSCs represent a useful cellular model to investigate novel drugs that may favor or, conversely, might prevent TL loss in human stem cells. The TL shortening is a permanent signature of previous chemotherapy-mediated DNA?damage, and predicts impaired proliferative and differentiation potential.     

Myeloablative doses of yttrium-90-ibritumomab tiuxetan and the risk of secondary myelodysplasia/acute myelogenous leukemia

BACKGROUND:

Because the long‐term toxicity of myeloablative radioimmunotherapy remains a matter of concern, the authors evaluated the hematopoietic damage and incidence of secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/AML) in patients who received myeloablative doses of the radiolabeled antibody yttrium‐90 (⁹⁰Y)‐ibritumomab tiuxetan.

METHODS:

The occurrence of sMDS/AML was investigated prospectively in 53 elderly patients with non‐Hodgkin lymphoma (NHL) who underwent an autograft after high‐dose radioimmunotherapy (HD‐RIT) myeloablative conditioning with ⁹⁰Y‐ibritumomab tiuxetan. Bone marrow (BM) hematopoietic progenitors and telomere length (TL) also were investigated.

RESULTS:

At a median follow‐up of 49 months, 4 patients developed sMDS/AML at 6 months, 12 months, 27 months, and 36 months after HD‐RIT, and the 5‐year cumulative incidence of sMDS/AML was 8.29%. A significant but transient decrease in BM granulocyte‐macrophage progenitors was observed; whereas multilineage, erythroid, and fibroblast progenitors were unaffected. A significant and persistent shortening of BM TL also was detected. A matched‐pair analysis comparing the study patients with 55 NHL patients who underwent autografts after chemotherapy‐based myeloablative conditioning demonstrated a 8.05% 5‐year cumulative incidence of sMDS/AML.

CONCLUSIONS:

HD‐RIT for patients with NHL was associated with 1) limited toxicity on hematopoietic progenitors, 2) accelerated TL shortening, and 3) non‐negligible incidence of sMDS/AML, which nevertheless was comparable to the incidence observed in a matched group of patients who received chemotherapy‐based conditioning. Thus, in the current series of elderly patients with NHL, the development of sMDS/AML was not influenced substantially by HD‐RIT. Cancer 2011;. © 2011 American Cancer Society.     

Bone marrow-derived cell mobilization by G-CSF to enhance osseointegration of bone substitute in high tibial osteotomy

Purpose

To evaluate granulocyte colony-stimulating factor (G-CSF) efficacy in accelerating bone regeneration following opening-wedge high tibial valgus osteotomy for genu varum.

Methods

A phase II trial was conducted for evaluating the preoperative administration of G-CSF given at 10 μg/kg/day for 3 consecutive days with an additional half-dose 4 h before the opening-wedge high tibial valgus osteotomy. Overall, 12 patients (Group A) received G-CSF treatment, and the subsequent 12 patients (Group B) underwent surgery without G-CSF. The osteotomy gap was filled by a bone graft substitute. Bone marrow cell (BMC) mobilization was monitored by CD34+ve cell and clonogenic progenitor cell analysis. All patients underwent a clinical (Lysholm Knee Scale and SF-36) and radiographic evaluation preoperatively, as well as at given intervals postsurgery.

Results

All patients completed the treatment program without major side effects; G-CSF was well tolerated. BMC mobilization occurred in all Group A patients, with median peak values of circulating CD34+ve cells of 110/μL (range 29–256). Circulating clonogenic progenitors paralleled CD34+ve cell levels. A significant improvement in Lysholm Knee Scale was recorded at follow-up in Group A compared to Group B. At the radiographic evaluation, there was a significant increase in osseointegration at the bone-graft junction in Group A at 1, 2, 3 and 6 months postsurgery compared to Group B. The computerized tomography scan of the grafted area at 2 months postsurgery showed no significant difference in the quality of the newly formed bone between the two Groups.

Conclusions

Although the limited number of patients does not allow firm conclusions, the study suggests that G-CSF can be safely administered preoperatively in subjects undergoing opening-wedge high tibial valgus osteotomy; in addition, the clinical, radiographic and CT monitoring indicate that G-CSF and/or mobilized BMCs may hasten bone graft substitute osseointegration.

Level of evidence

I.     

Lymphocyte transformation and autoimmune disorders

The many features that link autoimmune disorders (AD) and lymphoma are reviewed herein. Firstly, the epidemiology indicates the increased risk of non-Hodgkin's lymphoma (NHL) development in many AD, and especially in Sjögren's syndrome, rheumatoid arthritis and systemic lupus erythematosus. In these AD, the relative risk of NHL occurrence varies between 2 and 4 up to 40 fold higher than in the general population, according to various surveys. Factors favouring or predicting NHL have been reported in detail. B-cell activation and proliferation are part of AD and are essential factors for the onset of malignant cell clones in a deregulated immunological environment. Targeting deregulated or malignant B-cells is the goal of some newly developed treatments. The prototype is anti-CD20 rituximab that has substantially modified the prognosis of B-cell NHL and is also an effective new treatment opportunity for some AD. Similarly, intensified treatments with autologous haematopoietic stem cell transplant (ASCT) that were developed for high-risk lymphoma are now under advanced investigation for use in some refractory AD. Thus, the successful use of rituximab and ASCT in both AD and NHL further emphasizes the close link between these two entities. This review provides details on the main epidemiological features regarding NHL incidence in AD, the pathogenetic factors that favour lymphoma onset and some recent advances in therapeutic approaches that are effective in both autoimmune and malignant lymphoproliferative disorders.     

Use of the novel thrombopoietin receptor-agonist romiplostim, in combination with steroids and immunoglobulins for the increase of platelets prior to splenectomy, in refractory immune thrombocytopenia: a case report

This case report describes a patient with relapsed primary immune thrombocytopenic purpura (ITP), in which splenectomy was not possible due to the persistence of a low platelet count despite treatment with corticosteroids, intravenous immunoglobulins (IVIG) and platelet transfusion treatment. As an attempt to increase platelet count prior to performing splenectomy, the thrombopoietin receptor agonist, romiplostim, was administered in combination with steroids and IVIG. A single administration of romiplostim was found to be markedly effective, allowing a rapid and notable platelet increase, required for a well tolerated splenectomy. This case confirms the potent activity of romiplostim in ITP, and indicates that patients with recurrent primary ITP who are unresponsive to conventional immunosuppressive therapy may benefit from the addition of a short course of romiplostim.     

High Eu3+ concentration quenching in Y3TaO7 solid solution for orange-reddish emission in photonics

We report the synthesis of a Y₃TaO₇ solid solution containing a high Eu³⁺ concentration (from 7 up to 50 mol%) and investigate how Eu³⁺ influences the Y₃TaO₇ crystallization process. To this end, we evaluate the Y₃TaO₇ structural features and photoluminescence properties after Eu³⁺ introduction into the Y₃TaO₇ lattice. The higher the Eu³⁺ ion concentration, the more stable the crystallization process of the Y₃TaO₇ phase seems to be. The Eu³⁺-containing Y₃TaO₇ displays intense orange-reddish, broad band emission because Eu³⁺ occupies different symmetry sites in the host and causes inhomogeneous broadening. Eu³⁺ emission quenching due to Eu³⁺ concentration is negligible up to 30 mol% and absolute quantum yield values of up to nearly 30% were obtained, making Eu³⁺-containing Y₃TaO₇ interesting materials for application as high-intensity emitters in photonics.

Eu³⁺ ions influence on the crystallization process of Y₃TaO₇ solid solution and this particular host has presented a high concentration quenching (30 mol%), displaying an intense orange-reddish emission, with color purity over 92.6%.     

Rituximab-based pre-emptive treatment of molecular relapse in follicular and mantle cell lymphoma

Pre-emptive rituximab (pRTX) might represent an effective approach for patients with follicular (FL) and mantle cell lymphoma (MCL) experiencing molecular relapse (M-rel). However, available experience is still limited. We retrospectively collected FL and MCL cases that underwent pRTX with four weekly rituximab infusions (375 mg/m²) due to molecular persistence or M-rel. M-rel was assessed using nested polymerase chain reaction (PCR) and real-time quantitative PCR using the Bcl-1/IGH, Bcl-2/IGH or the immunoglobulin heavy chain rearrangement. Twenty-three occurrences of M-rel or persistence were treated in 18 patients (nine MCL and nine FL). The pRTX reinduced molecular remission (MR) in 17/23 cases (7/9 FL and 10/14 MCL). The median time to MR reinduction was 4.5 months (range 3–12), and the median duration of the first MR reinduction was 34 months (range 12–72). In five MCL cases, pRTX was used to treat subsequent M-rels, with success in four cases. No clinical relapses were seen within 2 years of successful reinduction of MR. Progression-free survival after pRTX was 64 % at a median follow-up of 6 years. pRTX was feasible and safe and effectively reinduced MR in FL and MCL patients (74 %). Prospective trials are needed to verify the clinical benefit of similar approaches.