Elena Tagliaferri

Hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: long-term results of a retrospective study on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Background Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the hemopoietic stem cells for which the only curative treatment is allogeneic hematopoietic stem cell transplantation. Design and Methods The aim of this retrospective study was to assess the long-term clinical and hematologic results in 26 paroxysmal nocturnal hemoglobinuria patients who received hematopoietic stem cell transplantation in Italy between 1988 and 2006. The patients were aged 22 to 60 years (median 32 years). Twenty-three donors were HLA-identical (22 siblings and one unrelated) and 3 were HLA-mismatched (2 related and one unrelated). Results Fifteen patients received a myeloablative conditioning consisting of busulfan and cyclophosphamide (in all cases from identical donor) and 11 were given a reduced intensity conditioning (8 from identical donor and 3 from mismatched donor). The cumulative incidence of graft failure was 8% (4% primary and 4% secondary graft failure). Transplant-related mortality for all patients was 42% (26% and 63% for patients transplanted following myeloablative or reduced intensity conditioning, respectively). As of October 31, 2009, 15 patients (11 in the myeloablative conditioning group and 4 in the reduced intensity conditioning group) are alive with complete hematologic recovery and no evidence of paroxysmal nocturnal hemoglobinuria following a median follow-up of 131 months (range 30–240). The 10-year Kaplan-Meier probability of disease-free survival was 57% for all patients: 65% for 23 patients transplanted from identical donor and 73% for 15 patients transplanted with myeloablative conditioning. No thromboembolic event nor recurrence of the disease were reported following transplant. Conclusions The findings of this study confirm that most patients with paroxysmal nocturnal hemoglobinuria may be definitively cured with hematopoietic stem cell transplantation.

The CIBMTR score predicts survival of AML patients undergoing allogeneic transplantation with active disease after a myeloablative or reduced intensity conditioning: a retrospective analysis of the Gruppo Italiano Trapianto Di Midollo Osseo

The CIBMTR score predicts survival of AML patients undergoing allogeneic transplantation with active disease after a myeloablative or reduced intensity conditioning: a retrospective analysis of the Gruppo Italiano Trapianto Di Midollo Osseo

Harvesting of Autologous Blood Stem Cells after a Mobilising Regimen with Low-dose Cyclophosphamide

Although high-dose cyclophosphamide (HD-CTX) is commonly used as a mobilising regimen for autologous peripheral blood stem cell (PBSC) collection, significant morbidity and insufficient harvesting may complicate the procedure. Alternative regimens and lower doses of cyclophosphamide (CTX) have been investigated as possible ways of overcoming these difficulties. Low-dose CTX (1.5 g/m 2 ) was administered to 102 lymphoma patients as an autologous PBSC mobilising regimen. The collection of 6 2 10 6 CD34+ cells/kg was chosen as the target of the apheresis sessions, whereas 3 2 10 6 /kg were considered the minimum necessary to perform autologous stem cell transplantation (ASCT) safely. The apheretic sessions were started a median of eight days after CTX administration; a median of two aphereses was required. More than 6 2 10 6 CD34+ cells/kg were collected from 78 patients, between 3 and 6 2 10 6 /kg from 19, and fewer than 3 2 10 6 /kg from 5, two of whom underwent bone marrow harvesting and one a successful second PBSC harvesting session using the same mobilising regimen. Eighty-two patients underwent autografting, six of whom received a second transplant after relapse (five using autologous PBSCs coming from the first apheretic course). Low-dose CTX proved to be a safe and effective regimen for autologous PBSC mobilization and also compared favourably with alternative regimens in terms of the rate of harvesting insufficiency. This does not imply that low-dose CTX is the best mobilising regimen for all patients, and the identification of prognostic factors predicting mobilising potential may help in choosing the best individualised regimen.

Autologous hematopoietic stem cell transplantation has better outcomes than conventional therapies in patients with rapidly progressive systemic sclerosis.

We retrospectively evaluated the efficacy of autologous hematopoietic stem cell transplantation (AHSCT) in 18 patients with rapidly progressive diffuse cutaneous systemic sclerosis (rp-dcSSc), and compared their disease outcomes with those of 36 demographically- and clinically-matched patients treated with conventional therapies. Cutaneous involvement, by performing modified Rodnan skin score (mRss), lung diffusion capacity, by measuring diffusing capacity of lung for carbon monoxide (DLCO), and disease activity, by applying the European Scleroderma Study Group (ESSG) scoring system, were the outcome variables measured at the baseline time and then every 12 months for the following 60 months in both the AHSCT-treated patients and the control group. In the AHSCT group, treatment-related mortality was 5.6%. In this group, both mRss and ESSG scores showed a significant reduction 1 year after AHSCT (P<0.002); and these results were maintained until the end of follow-up. Conversely, DLCO values remained stable during the whole period of follow-up. Survival rate of AHSCT group was much higher than that observed in the whole control group (P=0.0005). The probability that the ESSG score and mRss would remain at a high level, and DLCO could decrease, was significantly higher in the control group as a whole and in the subgroup of control patients treated with cyclophosphamide than in the AHSCT group. This study confirms that the AHSCT is effective in prolonging survival, as well as in inducing a rapid reduction of skin involvement and disease activity, and preserving lung function in patients with rp-dcSSc.

Retrospective evaluation of amphotericin B deoxycholate toxicity in a single centre series of haematopoietic stem cell transplantation recipients

events of nevirapine and efavirenz related to plasma concentrations? Antivir Ther 2005; 10: 489–98. 4. Isentress SPC (date of revision September 2008). electronic Medicines Compendium (eMC). http://emc.medicines.org.uk (13 October 2008, date last accessed). 5. Moreno A, Barcena R, Quereda C et al. Safe use of raltegravir and sirolimus in an HIV-infected patient with renal impairment after orthotopic liver transplantation. AIDS 2008; 22: 547–8.

Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report.

We present a case of severe, irreversible neurotoxicity in a 55‐year‐old‐patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory‐motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity.

IgD Multiple Myeloma Paraproteinemia as a Cause of Myositis.

A 48-years old man was diagnosed an IgD-k multiple myeloma (MM) at age 38 years for which he successfully underwent chemotherapy and bone marrow transplant. He then developed a graft-versus-host disease (GVHD) whose manifestations included, three years later, a polymyositis, diagnosed at muscle biopsy and successfully treated with steroids. Few months after polymyositis remission, myeloma relapsed and the patient was treated with thalidomide for six years with good remission. Soon after thalidomide suspension, MM relapsed again and the patient came to our observation for a new onset of neuromuscular symptoms. He underwent both muscle and peripheral nerve biopsy to discriminate between myositis (paraproteinemia versus GVHD), amyloidosis, and thalidomide toxicity. The first muscle biopsy showed an inflammatory pattern with necrotic fibres, macrophagical invasion (CD68 positive), rare interstitial cellular infiltrates (CD8 positive and CD4 negative), widespread anti-HLA positivity and negative antiMAC. The second muscle biopsy showed the same inflammatory pattern plus an involvement of blood vessels. Direct immunofluorescence for IgD showed diffuse positivity along the sarcolemmal in both muscle biopsies. Sural nerve biopsy demonstrated both demyelinating and axonal aspects with no inflammatory infiltrates, but positivity for HLA and MAC. Congo Red was negative in both skeletal muscle and peripheral nerve.

Quantiferon CMV assay in allogenic stem cell transplant patients

• Clinical utility of measuring CMV-specific CD8 + T cell response as a prognostic tool is evaluated.

G-CSF after autologous hemopoietic stem cell transplantation in malignant lymphoma

Forty-eight autografted patients were studied after treatment with granulocyte-colony stimulating factor (G-CSF) and were compared with a historical series of 24 patients autografted with bone marrow (BM) without G-CSF. When the patients were divided on the basis of G-CSF administration, type of lymphoma and the source of hemopoietic stem cells, no significant difference was found in the median number of infused BM cells, duration of febrile episodes, platelet and hemoglobin recovery, or in the number of transfusions. The patients receiving peripheral blood (PB) + G-CSF had significantly shorter median durations of antibiotic therapy, hospital stay and polymorphonucleate (PMN) recovery. When the Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) cases were considered separately, a significant difference between those receiving and those not receiving G-CSF was observed only in the HD group. The advantage offered by PB + G-CSF over BM + G-CSF was far more evident in the NHL group than in HD. It can be concluded that G-CSF improves the outcome of BM transplant in HD, and that the use of PB + G-CSF adds a further advantage; conversely, in NHL, PB + G-CSF is strikingly superior to BM + G-CSF, but the addition of G-CSF adds little advantage.

Autologous Bone Marrow Transplantation in Advanced Hodgkin's Disease

Autologous bone marrow transplantation (ABMT) has been proposed as an alternative treatment of resistant/refractory Hodgkins disease (HD). Thirty-seven patients in various phases of HD underwent autografting in our Center: fourteen received a CBV conditioning regimen, the others BCNU or VP16 followed by cyclophosphamide and TBI. Three patients died before engraftment, 28 (75.67%) achieved CR and 6 showed persistent disease. As of March 1996, 18 patients had died and 13 were in continuous CR. The median event-free survival (EFS) and 3-year EFS chances were respectively 9 months and 31.3% in the series as a whole, 14 months and 40% in primary resistant disease, 9 months and 28.4% in responsive relapse, and 3 months and 22.2% in resistant relapse. As many of these patients had failed to respond to third-line therapies, their EFS figures are primarily attributable to the therapeutic efficacy of ABMT. Furthermore, since the EFS curves are better in patients seemingly characterized by a lower chance of chemoresistance, our data favour the use of ABMT in the earlier phases of HD.