Efficacy and safety of splenectomy in adult autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) is a rare hematologic disease, primarily affecting adults or children with immunodeficiency disease. First-line therapy consists of long course of steroids administration, with an early complete response rate (CRr) of 75-80%, but up to 20-30% of patients requires a second-line therapy. Rituximab is the first choice in refractory old AIHA patients, because of its safety and efficacy (early CRr at 80-90% and at 68% at 2-3 years). For this reason, splenectomy is even less chosen as second-line therapy in elderly, even though laparoscopic technique decreased complication and mortality rates. However, splenectomy can be still considered a good therapeutic option with a CRr of 81% at 35.6 months in patients older than 60 year-old, when rituximab administration cannot be performed

Reproductive issues in patients undergoing Hematopoietic Stem Cell Transplantation: an update.

In 1963 George Mathé announced to the world that he had cured a patient of leukaemia by means of a bone-marrow transplant. Since than much progress has been made and nowadays Hematopoietic Stem Cell Transplantation (HSCT) is considered the most effective treatment of numerous severe haematological diseases. Gynaecological complications in HSCT women represent a serious concern for these patients, but often underestimated by clinicians in the view of Overall Survival. The main gynaecological complications of HSCT are represented by: premature ovarian failure (POF), thrombocytopenia-associated menorrhagia, genital symptoms or sexual problems in course of chronic GVHD (cGVHD), osteoporosis, secondary solid tumours due to immunosuppressive drugs to treat cGVHD and severity of cGVHD, and fertility and pregnancy issues. In particular fertility-related issues are always more relevant for patients, whose life expectation is constantly growing up after HSCT.Thus, taking care of a patient undergoing HSCT should primarily include gynaecological evaluation, even before conditioning regimen or chemotherapy for the underlying malignancy, as, in our opinion, it is of great importance to ensure a complete diagnostic work-up and intervention options to guarantee maximum reproductive health and a better quality of life in HSCT women.The present review aims at describing principal features of the aforementioned gynaecological complications of HSCT, and to define, on the basis of current international literature, a specific protocol for the prevention, diagnosis, management and follow-up of gynaecological complications of both autologous and heterologous transplantation, before and after the procedure

Fine needle aspiration biopsy of intraparotid spindle cell lipoma: A case report.

Intraparotid spindle cell lipoma (SCL) of the salivary gland is a rare entity. Review of the literature revealed only two previous reports describing its cytological features. We report a case of a 44-year-old man who complained for a slowly growing, asymptomatic mass in the left parotid gland that since 12 months. Fine needle aspiration biopsy (FNAB) showed a loose collections of bland-appearing spindle cells in a myxoid background admixed with capillary fragments and some mature fat cells suggesting a diagnosis of SCL. A cytological diagnosis of mesenchymal myxoid spindle cell tumor with lipomatous differentiation, possibly an intraparotideal SCL was performed. Histological examination of the mass and the positive immunostaining for CD34 and negativity for S-100, CK-cocktail, and actin confirmed the diagnosis of SCL. The diagnosis of intraparotid SCL can be made by examining cytologic material containing mature fat with bland spindle cells in a myxoid background. FNAB diagnosis on SCL also allows to rule out other primary salivary gland tumors that may be clinically and instrumentally indistinguishable and thereby permits an appropriate surgical procedure to ensue

Upar soluble forms and hematopoietic stem cell transplantion

The urokinase (uPA)-type plasminogen activator receptor (uPAR) is expressed on the surface of various cell types, both in full-length and cleaved forms, lacking the N-terminal DI domain. uPAR binds uPA and vitronectin (VN) and regulates integrin activity. uPAR can be shed from the cell surface, generating full-length and cleaved soluble forms (suPAR and DIIDIII-suPAR, respectively). suPAR is still able to bind uPA and VN, unlike DIIDIII-suPAR, which, however, if exposing the sequence SRSRY (aa 88-92) at its N-terminus, is able to bind the chemotactic receptors for fMLF. Soluble forms of uPAR have been detected in human fluids. We previously demonstrated the involvement of uPAR soluble forms in G-CSF-induced human CD34+ hematopoietic stem cell (HSC) mobilization. Further, we demonstrated that DIIDIII-suPAR can induce mobilization of hematopoietic stem/progenitor cells in mice. Since HSC mobilization and homing to bone marrow (BM) are specular processes which utilize same mediators and similar signaling pathways, we investigated whether the soluble forms of uPAR could be also involved in HSC homing and engraftment to the BM. Firstly, we examined suPAR and DIIDIII-suPAR expression in cultures of human BM stroma cells. Interestingly, stroma cells produced suPAR and high amounts of the chemotactic DIIDIII-suPAR. We then evaluated the levels of both suPAR forms in sera from four healthy donors and from five patients before and after the pretransplant conditioning with chemotherapy. We found a significant increase only in DIIDIII-suPAR levels in sera from patients before conditioning, as compared to healthy donors; however, the chemotherapy conditioning significantly decreased circulating DIIDIIIsuPAR levels. We also examined the potential effects of the different soluble forms of uPAR in long term cultures (LTC) of G-CSF-mobilized CD34+ HSCs, in the presence of suPAR or of the uPAR84-95 peptide, corresponding to the active site of DIIDIII-suPAR. Both suPAR and the uPAR84-95 peptide increased the number of adherent clonogenic progenitors in LTC of G-CSF mobilized HSCs. Altogether, our results suggest that BM stroma produces soluble forms of uPAR which could contribute to the engraftment of CD34+ HSC to BM. According with our previous observation on the mobilizing effects of DIIDIII-suPAR, the circulating cleaved suPAR seems to be lowered by pretransplant conditioning, probably to allow CD34+ HSC homing

Continuous maintenance therapy with alternate-day low dose lenalidomide in multiple myeloma patients after autologous stem cell transplantation

Maintenance therapy with immunomodulatory drugs has shown to improve responses and delay relapse and progression in Multiple Myeloma (MM) patients after autologous stem cell transplantation (ASCT). Although maintenance therapy with Thalidomide (T) after ASCT increases progression free survival (PFS) in MM patients, it is associated with dose-limiting multiple toxicities. Lenalidomide (R), approved for relapsed and/or refractory MM, has been reported to be associated with lower rates of toxicities than T. We evaluated efficacy and safety of continuous maintenance therapy with alternate-day low dose R (LD-R, 10 mg/day), after high-dose melphalan (HD-MEL, 200 mg/mq) and ASCT, in 8 MM patients (6 male and 2 female) older than age 60 (median: 68 years, range 60-73), receiving pre-ASCT induction treatment with 4 cycles of conventional bortezomib, T and dexamethasone (VTD) regimen. Of these 8 MM patients, 2 and 6 patients were in complete remission (CR) and in very good partial remission (VgPR) after ASCT, respectively. After a median follow-up of 14 months (range 3-43) from the initiation of LD-R maintenance, patients in CR maintained their CR, and all patients in VgPR improved the depth of response except one who showed disease progression. In this LD-R group, PFS and overall survival (OS) at 24 months were 83% and 100%, respectively, and no significant specific R-related toxicity was encountered. LD-R maintenance therapy was retrospectively compared with a matched age, gender, disease stage cohort of 17 MM patients treated with low-dose T (LD-T) maintenance therapy (50 mg/day for 2 years) after HD-MEL ASCT. In this last cohort, after a median follow-up of 53 months (range 3-125), 8/17 (47%) patients relapsed, and median PFS and OS were 39 and 53 months, respectively. In LD-T group, grade I-III neurotoxicity was detected in 11/17 (65%) patients, increasing up to 80% after 2 years of therapy, leading to drug discontinuation in 4/17 (23%); in addition, grade I hematological toxicity was documented in 55% of patients. PFS and OS were not statistically significant between these two groups of patients. Our preliminary results provide evidence that continuous therapy with alternate-day LDR is a feasible and effective maintenance treatment after ASCT for MM patients enabling a long-lasting maintenance therapy. These results require further validation in prospective larger studies

Continuous alternate-day low dose lenalidomide in combination with low dose prednisone as frontline treatment for octogenarian newly diagnosed multiple myeloma patients

About 30% of patients with newly diagnosed multiple myeloma (NDMM) are older than 75 years. Immunomodulatory drugs (IMIDs) have improved response rates and outcomes of NDMM, except for patients older than 75 years more vulnerable to side effects of IMIDs because of their frailty and comorbidities. We evaluated efficacy, toxicity and health-related quality of life (HRQOL) associated with continuous alternate-day low dose lenalidomide (LD-R, 10 mg on alternate days) and low dose prednisone (15 mg/day) (LD-RP) in 7 octogenarian NDMM patients (5 males and 2 females) with a median age of 82 years (range 80-87). All octogenarian patients had IgG MM, except 1 oligosecretory lambda chain MM; all were in Durie-Salmon stage III, except 1 in stage II, and had poor WHO performance status (median: 2, range 1- 3). Patients were evaluated at baseline and every 6 months for HRQOL according to MM-specific questionnaire QLQ-MY20 of European Organization for Research and Treatment of Cancer (EORTC). All patients received aspirin thromboprophylaxis, 57% of them requiring from diagnosis erythropoietin and zoledronic acid treatment. In these 7 octogenarian NDMM patients completing at least three months of therapy, the overall response rate (ORR) was 86%, including 1 complete remission (CR), 2 very good partial remission (VgPR) and 3 PR. After a median follow-up of 12 months (range 3-24), the quality of response improved with continuous LD-RP treatment with a cumulative median reduction in monoclonal protein levels of 85% (range 20-100%); none of the patients required discontinuation of treatment secondary to specific hematologic and/or extra-hematologic toxicity. In addition, QLQ MY-20 questionnaires revealed that 70% of patients treated with continuous LD-RP reported improvements of QOL scores. Two out of 7 octogenarian patients died (1 for progression after 12 months and 1 for sepsis no treatment-related), and 2-year overall survival and progression-free survival estimates were 41% and 75%, respectively. Noteworthy, all patients treated with continuous alternate-day LD-RP showed progressive increase of circulating CD56+, CD3- natural killer cells regardless of treatment response. Our data provide evidence that continuous alternate-day low dose lenalidomide is a manageable and effective frontline treatment for octogenarian NDMM patients. These preliminary results require further validation in prospective larger studies

Role of Laparoscopic Splenectomy in Elderly Immune Thrombocytopenia.

The management of older patients with chronic primary immune thrombocytopenia (ITP) is still very challenging because of the fragility of older patients who frequently have severe comorbidities and/or disabilities. Corticosteroid-based first-line therapies fail in most of the cases and patients require a second-line treatment, choosing between rituximab, thrombopoietin-receptor agonists and splenectomy. The choice of the best treatment in elderly patients is a compromise between effectiveness and safety and laparoscopic splenectomy may be a good option with a complete remission rate of 67% at 60 months. But relapse and complication rates remain higher than in younger splenectomized ITP patients because elderly patients undergo splenectomy with unfavorable conditions (age >60 year-old, presence of comorbidities, or multiple previous treatments) which negatively influence the outcome, regardless the hematological response. For these reasons, a good management of concomitant diseases and the option to not use the splenectomy as the last possible treatment could improve the outcome of old splenectomized patients

Mesenchymal stem cells from the Warton'Jelly of the human ombelical cord: biological properties and therapeutic potential

Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiative potential, an immuno-privileged status and easy access for collection, which raise no legal or ethical issues. WJ-MSCs exhibit several features of embryonic stem cells, both in the phenotypic and genetic aspects, with only a few differences, such as a shorter doubling time and a more extensive ex vivo expansion capacity. WJ-MSCs have mmunomodulatory properties, involving both innate and adaptive immune responses. This review focuses on the role of WJ-MSCs in the management of graft-versus-host disease (GvHD), a life-threatening complication of the allogenic transplantation of hematopoietic stem cells. Different studies documented the beneficial effect of the infusion of WJ-MSCs, even when not fully HLA identical, in patients with severe GvHD, refractory to standard treatment. Finally, we summarized current ongoing clinical trials with WJ-MSCs and their potential in regenerative medicine