Roberta Destro

Extracorporeal photochemotherapy may improve outcome in children with acute GVHD

Acute GVHD (aGVHD) is a major cause of morbidity and mortality after unrelated BMT (UBMT). Our purpose was to analyze the role of extracorporeal photochemotherapy (ECP) in controlling grade II–IV aGVHD in children given UBMT. Of 41 consecutive children, 31 developed grade II–IV aGVHD after UBMT: 16 had a good response to steroids (GR group), whereas 15 underwent ECP (ECP group) within 100 days of UBMT. Eligibility criteria for starting ECP were steroid resistance, dependence or viral reactivations. Criteria for judging response to aGVHD treatment were that the resolution of all signs were considered a complete response (CR), at least a 50% improvement was classified as a partial response (PR) and stable or progressive disease was judged as no response (NR). On completing ECP, the CR rate was 73%, whereas the GR group had a CR rate of 56% by day 100. The 2-year overall survival and progression-free survival rates were 57 and 67% in the GR group vs 85 and 87% in the ECP group. Our data seem to suggest that ECP may improve outcome in patients after UBMT. These findings need to be confirmed in a larger population.

Mesenchymal stromal cells can be derived from bone marrow CD133+ cells: implications for therapy.

It is known that the bone marrow (BM) CD133(+) cells play an important role in the hematopoietic compartment, but this is not their only role. The cells indeed can take part in vascular reconstitution when they become endothelial cells (EC), in skeletal muscle fiber regeneration when there is a switch in muscle precursors, and to cardiomyocyte phenotypic conversion when differentiating in cardiomyocytes-like cells. While the role in hematopoiesis and vasculogenesis of the selected cells is well established, their ability to differentiate along multiple non-EC lineages has not yet been fully elucidated. The goal of this study is to assert whether human CD133(+)BM-derived cells are able to differentiate in vitro, besides to blood cells, cell lineages pertinent to the mesoderm germ layers. To this end, we isolated CD133(+) cells using a clinically approved methodology and compared their differentiation potential to that of hematopoietic progenitor cells (HPCs) and mesenchymal stem cells (MSCs) obtained from the same BM samples. In our culture conditions, CD133 expression was consistently decreased after passage 2, as well as the expression of the stemness markers c-kit and OCT4, whereas expression of Stage Specific Embryonic Antigen 4 (SSEA4) remained consistent in all different conditions. Expanded CD133 were also positive for HLA-ABC, but negative for HLA-DR, in accordance with what has been previously reported for MSCs. Moreover, CD133(+) cells from human BM demonstrated a wide range of differentiation potential, encompassing not only mesodermal but also ectodermal (neurogenic) cell lineages. CD133 antigen could be potentially used to select a cell population with similar characteristics as MSCs for therapeutic applications.

Successful unrelated bone marrow transplantation for Shwachman–Diamond syndrome

A 5-year-old boy with Shwachman–Diamond syndrome underwent unrelated HLA-identical bone marrow transplantation for severe pancytopenia. Conditioning was with busulfan, thiotepa and cyclophosphamide plus rabbit anti-lymphocyte serum. Engraftment for neutrophils and platelets was observed on days +18 and +41, respectively. Transplant-related side-effects were mild and transient. After a follow-up of 32 months, the patient is alive and enjoys a normal life, off any immunosuppressives. Immunological and hematological reconstitution is complete while other phenotypic characteristics (pancreatic insufficiency, short stature, femur dysostosis) are stable. Although experience in this field is scarce, we speculate that bone marrow failure in Shwachman–Diamond syndrome (even if not linked to the appearance of clonal disorders or leukemic transformation) is an indication for bone marrow transplantation and may be associated with a better outcome. Bone Marrow Transplantation (2001) 27, 97–99.

Successful treatment of secondary acute myeloid leukemia relapsing after allogeneic bone marrow transplantation with donor lymphocyte infusion failed to prevent recurrence of primary disease: a case report

We report a case of therapy-related secondary acute myeloid leukemia occurring in a patient during treatment for anaplastic large cell lymphoma. In spite of response to induction chemotherapy and prompt bone marrow transplantation from his matched sister, the patient experienced an early leukemia relapse within 3 months of the transplant. Treatment with oral etoposide for 3 weeks followed by donor lymphocyte infusion achieved a 7-month remission from leukemia without any further treatment. Unfortunately, the patient suffered a recurrence of the primary anaplastic large cell lymphoma that was treated by resuming chemotherapy and local radiotherapy. The patient died 20 months after DLI, still in CR for his leukemia, due to ALCL progression.

Non-T, non-B childhood acute lymphoblastic leukemia. Correlation between cytochemical markers and first complete remission

The positivity for four cytochemical reactions, acid phosphatase (AcP), alpha‐naphtyl acid acetate esterase (ANAE), beta‐glucuronidase (BG), and N‐acetyl beta‐glucosaminidase (NABG) was correlated to first remission duration in 120 children affected with non‐T, non‐B acute lymphoblastic leukemia (ALL). The percentages of patients remaining in complete remission at 72 months were always higher for children whose blasts lacked these enzymatic reactions; however, a statistical difference was found only between BG+ and BG− ALL. It also appears that more complete enzymatic patterns of leukemic cells are associated with a poorer prognosis. The percentage of patients still in their first remission was 89% for leukemias with no cytochemical markers, 59% when one reaction was present, but less than 39% when two or more enzymes were detected in the blasts. It is noteworthy that the blasts of patients with more severe prognosis demonstrated a simultaneous positivity for AcP–ANAE or BG–NABG cytochemical reactions. The possible usefulness of these cytochemical markers to detect subsets of patients with different prognostic significance among non‐T, non‐B ALL is discussed.

Focal nodular hyperplasia of the liver: an emerging complication of hematopoietic SCT in children

Hepatic focal nodular hyperplasia (FNH) is a nonmalignant condition rarely affecting children previously treated for cancer, especially those who received hematopoietic SCT (HSCT). Some aspects of its pathogenesis still remain unclear and a strong association with specific risk factors has not yet been identified. We report here a single institutions case series of 17 patients who underwent HSCT and were diagnosed with FNH, analyzing retrospectively their clinical features and the radiological appearance of their hepatic lesions. We aimed to compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) and to explore the role of transient elastography (FibroScan) to evaluate the degree of hepatic fibrosis in FNH patients. Our analysis showed an association of FNH with age at transplant ⩽12 years (hazard ratio (HR) 9.10); chronic GVHD (HR 2.99); hormone-replacement therapy (HR 4.02) and abdominal radiotherapy (HR 4.37). MRI proved to be a more accurate diagnostic tool compared with US. Nine out of 12 patients who underwent FibroScan showed hepatic fibrosis. Our study points out that FNH is an emerging complication of HSCT, which requires a lifelong surveillance to follow its course in cancer patients.