Haploidentical hematopoietic stem cell transplantation in a myelofibrosis patient with primary graft failure

The prognosis of patients affected by myelofibrosis (MF) is usually dismal and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only cure. The number of HSCTs in MF patients has recently increased. However, a major obstacle is still represented by primary graft failure (PGF). Currently there are no definitive guidelines for the treatment of PGF and a second HSCT can be performed only when an allogeneic donor is rapidly available. Herein we report on a MF patient with PGF after an unrelated HSCT, who was rescued by a non-myeloablative, unmanipulated, haploidentical HSCT that resulted in persistent engraftment and bone-marrow fibrosis regression, but not in a long-term disease control. Based on this experience we briefly review the role of different conditioning regimens and hematopoietic stem cell sources in the setting of HSCT for MF patients with PGF. The role of haploidentical donors in MF patients lacking HLAmatched relatives is also discussed

Haploidentical hematopoietic stem cell transplantation in a myelofibrosis patient with primary graft failure

The prognosis of patients affected by myelofibrosis (MF) is usually dismal and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only cure. The number of HSCTs in MF patients has recently increased. However, a major obstacle is still represented by primary graft failure (PGF). Currently there are no definitive guidelines for the treatment of PGF and a second HSCT can be performed only when an allogeneic donor is rapidly available. Herein we report on a MF patient with PGF after an unrelated HSCT, who was rescued by a non-myeloablative, unmanipulated, haploidentical HSCT that resulted in persistent engraftment and bone-marrow fibrosis regression, but not in a long-term disease control. Based on this experience we briefly review the role of different conditioning regimens and hematopoietic stem cell sources in the setting of HSCT for MF patients with PGF. The role of haploidentical donors in MF patients lacking HLAmatched relatives is also discussed

Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases

The trisomy 8 found in malignancies may derive from a constitutional trisomy 8 mosaicism (CT8M), and in these cases the trisomy itself may be regarded as the first mutation in a multistep carcinogenetic process. To assess the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8, an informative sample of 14 patients was collected. The data ascertained included chromosome analyses of fibroblast cultures and of PHA-stimulated blood cultures in patients with normal blood differential count, as well as possible CT8M clinical signs. One patient showed trisomy 8 in all cell types analyzed and undoubtedly has a CT8M; a second patient consistently showed trisomy 8 in PHA-stimulated blood cultures when no immature myeloid cells were present in blood and should be considered as having CT8M; a third patient, with Philadelphia-positive chronic myelocytic leukemia, was more difficult to interpret, but the possibility that she had CT8M is likely. A few clinical signs of CT8M were also present in these three patients. Our data indicate that the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8 is approximately 15\u201320%

Expression and function of the TL1A/DR3 axis in chronic lymphocytic leukemia

TNF-like ligand 1A (TL1A) and its unique receptor death receptor 3 (DR3) acts as broad T-cell costimulator involved in regulatory mechanisms of adaptive immune response under physiological and pathological settings. Moreover, we have recently shown that TL1A negatively regulates B-cell proliferation. Despite increasing interest on the TL1A/DR3-axis functions, very little is known on its expression and role in leukemia. In this study, we investigated the expression and function of TL1A/DR3 axis in chronic lymphocytic leukemia (CLL). DR3 was differentially expressed in activated CLL cells and predominantly detected in patients with early clinical stage disease. Soluble TL1A has been revealed in the sera of CLL patients where higher TL1A levels were associated with early stage disease. T cells, monocytes and leukemic B cells have been identified as major sources of TL1A in CLL. The relevance of these findings has been sustained by functional data showing that exogenous TL1A reduces CLL proliferation induced by stimulation of the B cell receptor. Overall, these data document the expression of the TL1A/DR3 axis in early-stage CLL. They also identify a novel function for TL1A as a negative regulator of leukemic cell proliferation that may influence the CLL physiopathology and clinical outcome at an early-stage disease

Primers used to amplify and sequence P53, Card 11, CD79B, MYD88 AND RPMS1 genes.

<p>Isoform 1: 858 pb; Isoform 2: 546 pb; Isoform 3: 861 pb.</p

Summary of VR09 cell line features.

<p>Summary of VR09 cell line features.</p

Karyotyping and FISH of secondary culture.

<p>(A) Trisomy of chromosome 12 and structural chromosome aberration involving chromosomes 7 and 9 on secondary culture detected by karyotype; (B) Chromosome 9 staining by FISH of secondary culture.</p

EBV positivity in the original tumor and in the VR09 cell line.

<p>PCR products analysis by Agilent 2100 Bioanalyzer showed the presence of the same 151 bp specific amplicon for EBV RPMS1 gene, thus demonstrating that EBV infection was present in the original cells from patient. A normal DNA from pancreas was used as negative control.</p

Morphology of primary malignant cells and VR09 cell line.

<p>Morphological features of patient’s primary cells and VR09 cells in suspension, as assessed by May-Grünwald-Giemsa staining. (A) Patient’s peripheral blood cells. (B) Patient’s bone marrow cells. (C) VR09 cells: small and round clumps in suspension. (D) VR09 cells: plasmacytoid appearance, with irregular nucleus, compact chromatin and abundant basophilic cytoplasm.</p