Davide Rapezzi

Reversible dasatinib-induced pulmonary arterial hypertension and right ventricle failure in a previously allografted CML patient

Reversible dasatinib-induced pulmonary arterial hypertension and right ventricle failure in a previously allografted CML patient

Influenza vaccine in chronic lymphoproliferative disorders and multiple myeloma.

Objective: Vaccination against influenza in patients with chronic lymphoproliferative disorders (CLPD) and multiple myeloma (MM) is still a matter of clinical uncertainty. The aim of this study was to determine the safety, immunogenicity and clinical response to a commercially available vaccine against influenza in a group of such patients.

Heterogeneity of clonal development in chronic myeloproliferative disorders

Recent reports have suggested a previously unexpected variability in the expression of the dominant neoplastic clone in myeloproliferative disorders (MPD). We evaluated 49 female patients with MPD and informative at the X‐linked androgen receptor (AR) locus to establish the X chromosome inactivation pattern of hemopoietic cells. Whereas in chronic myelogenous leukemia (CML) the granulocytes (PMN) were uniformly of monoclonal origin, a striking heterogeneity of clonal development was found in PMN from patients with other MPD, with up to 50% of them expressing a polyclonal pattern of X inactivation. Am. J. Hematol. 60:158–160, 1999.

Imatinib and ruxolitinib association: first experience in two patients

We report the first case of 2 patients with a previous diagnosis of post-polycythemic (PV) myelofibrosis who developed chronic myeloid leukemia (CML) seven years later, both treated with an association of a tyrosine-kinase inhibitor (imatinib) and a JAK1/JAK2 inhibitor (ruxolitinib). In 1992, a 46-

Early Chemotherapy Intensification With Escalated BEACOPP in Patients With Advanced-Stage Hodgkin Lymphoma With a Positive Interim Positron Emission Tomography/Computed Tomography Scan After Two ABVD Cycles: Long-Term Results of the GITIL/FIL HD 0607 Trial

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

Peripheral Blood CD34+ Percentage at Hematological Recovery after Chemotherapy Is a Good Early Predictor of Harvest: A Single-Center Experience

Several algorithms for early prediction of poor-mobilizing patients after chemotherapy and granulocyte colony-stimulating factor administration have been proposed. They generally define peripheral blood cut-off levels of CD34+ cells at a fixed day after starting chemotherapy, mostly with cyclophosphamide. To define an algorithm for early addition of plerixafor regardless of the chemotherapy regimen used, we retrospectively analyzed 280 chemomobilization attempts in 236 patients treated at our institution between 2002 and 2012. In multivariate analysis, CD34+ absolute count and CD34+ percentage upon total leukocyte count at day 1 (defined as the first day in which leukocytes reached a value > 1 × 10(9)/L) were the only factors able to predict a total harvest ≥ 2 × 10(6) CD34+/kg. In patients with day 1 CD34+ lower than 20/μL, the CD34+ percentage was a more reliable predictor of stem cell harvest in the following days than CD34+ absolute count. Upon definition of the best CD34+ cut-off value for identification of poor-mobilizing patients, an algorithm was set up to guide plerixafor administration. It was prospectively validated in 20 patients in 2013 with encouraging results in terms of low incidences of both mobilization failure and plerixafor use. Large prospective trials that define the most cost-effective strategy for just-in-time rescue plerixafor are warranted.

Clonal granulocytes in polycythaemia vera and essential thrombocythaemia have shortened telomeres

The purpose of this study was to evaluate telomere length in peripheral blood granulocytes and mononuclear cells collected from 22 women with polycythaemia vera (PV) and essential thrombocythaemia (ET). PV and ET are chronic myeloproliferative diseases whose heterogeneity of stem cell origin and clonal development has been established through analysis of X‐chromosome inactivation patterns. The results from clonality assay and determination of telomere length show that only clonal granulocytes have shortened telomeres.

Survival of people who are HIV-1-positive and G6PD-deficient is unaffected by virus-induced oxidative stress

There is interest in the part played by free radicals and glutathione in HIV-1 infection. Because glucose-6phosphate dehydrogenase (G6PD) is the main enzyme responsible for maintaining glutathione in its reduced form (GSH), we compared the survivals of HIV-1-infected people carrying the normal G6PD allele (Gd) or the Mediterranean variant (Gd). People with Gd have almost undetectable erythrocyte G6PD activity, and mononuclear cells from peripheral blood express 20–25% of the normal amount of enzyme. People with the defect are unable to maintain adequate concentrations of GSH and should therefore be more prone to oxidation of GSH after an induced oxidative stress such as that reported to occur during HIV-1infection. From 1983 to 1996, 323 consecutive HIV-1-positive men from Northern Sardinia, an area where about 8% of men have the Gd mutation, were screened for G6PD deficiency. 27 were Gd. No significant difference was found between those with and without the mutation in age at diagnosis, risk factors for HIV-1-infection, CD4 T cells count, or incidence and type of opportunistic infections. No haemolytic crises were observed in the Gd group during the follow-up period. Disease progression was estimated from the first HIV-1-positive test until December, 1996, or death. The median survival of the patients was 93 months for both groups (range 6–166 for the Gd and 8–151 for the Gd, respectively); -test for trend: p=0·18 (figure). Overall, 55 people with Gd (18·6%) and eight with Gd (29·6%) were dead by the end of the follow-up period. 98 people in the Gd group (33·1%), and ten in the Gd (37·0%) developed AIDS. Those with Gd did not progress to AIDS more rapidly than those with Gd (64·1 months for the Gd and 61·2 for the Gd, p=0·83). Likewise, G6PD deficiency did not affect survival in those who developed AIDS: they had a median survival of 82 months with Gd (range 6–159) and 71 months with Gd (range 8–124); test for trend: p=0·27 (figure). At least under the conditions of our study, oxidative stress is unlikely to play a large part in progression of HIV-1infection. The low concentrations of GSH reported by some census. As the ISTAT procedure could provide information on parents’ place of birth only for children living with both parents (92·6% of the number of children under 15) all the denominators were adjusted for this figure. The children were classified in three groups according to place of birth of the parents, as both born in Sardinia, only one born in Sardinia, or both born in other region of Italy. We also considered an independent source: the demographic files of Milan for the years 1989–93 including all the residents (around 11% of the region’s residents), and for each year we estimated the fraction of children under 15 with at least one Sardinian parent. The average figure was 3·6%, very close to the 3·8% regional ISTAT estimate. The figure shows the observed annual rates of IDDM incidence for children according to parents’ birth place: 26·1/100 000 (CI 7·1–66·8) for the four children with both parents born in Sardinia; 15·6/100 000 (CI 8·9–25·4) for the 16 children with only one parent born in Sardinia; and 7·8/100 000 (CI 7·1–8·5) for children with no parents born in Sardinia. Children with one parent born in Sardinia had a relative risk of developing IDDM of 2·0 (CI 1·2–3·3) compared with children with both parents born outside Sardinia. The relative risk for children born from two Sardinian parents was 3·4 (CI 1·3–9·0). The expected number of cases, assuming the same rate as the Sardinian population, is 5·3 for children of both parents born in Sardinia. On the other hand, the number of observed IDDM cases with only one Sardinian parent is about less than half the number of expected cases (35·2) by the Sardinian incidence rate. By means of a telephone interview with the cases we found only a very low exposure to the Sardinian environment (time spent in the island, supply of Sardinian food before the onset of IDDM, and diabetes family history). The same data were used to provide a Lombardy incidence rate of IDDM among children less than 15 years, estimated after validation by two other independent sources. The expected incident cases, obtained by the capture-recapture method, were 586·2, with an annual incidence rate of 9·5/100 000 (CI 8·8–10·3/100 000). Our results confirm a high IDDM incidence in Sardinianheritage children who live in a low IDDM incidence region.

Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms

We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment.

Long-term results of rituximab treatment for membranous nephropathy after allogeneic hematopoietic SCT: a case report

Long-term results of rituximab treatment for membranous nephropathy after allogeneic hematopoietic SCT: a case report