Panagiotis Tsirigotis

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): treatment outcome, relapses, prognostic factors. A single-center experience of 48 cases.

Abstract The thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) is a rare disorder characterized by microangiopathic hemolysis and thrombocytopenia. We have undertaken a retrospective analysis of the clinical characteristics, treatment outcome, and prognosis of 48 patients diagnosed and treated in our institution during a 13-year period. Among our patients 22 (46%) had fever, 35 (73%) neurological abnormalities, and 22 (46%) renal impairment at presentation of the syndrome. All patients were treated with a multimodality regimen including plasma exchange, steroids, antiplatelet agents, and IgG infusion. Of the 48 patients, 41 achieved complete remission, two had a partial response, and five had no response and died of progressive disease. Within a median follow-up period of 40 months, ten of the 41 patients who had achieved remission relapsed, most of them within the first 2 years, and nine of these responded promptly to plasma exchange therapy. Eight deaths were observed, seven of refractory disease and one in fourth relapse. The analysis of prognostic factors revealed advanced age and severe renal impairment (creatinine levels above 2 mg%) as the only parameters associated with treatment failure and poor outcome. However, none of the pretreatment characteristics proved to be of prognostic value regarding the probability of relapse. In conclusion, TTP/HUS represent a syndrome of variable clinical expression and aggressiveness. The use of a multimodality regimen in our series produced a high response rate. Nevertheless, the early identification, based on clinical characteristics, of poor-prognosis cases that probably need more or alternative forms of treatment is an issue that remains to be elucidated in prospective trials.

Primary adrenal lymphoma presenting as Addison’s disease: case report and review of the literature

Primary adrenal lymphoma (PAL) is an extremely rare entity and adrenal insufficiency is a common complication. Bilateral enlargement of adrenal glands should raise the suspicion of lymphoma, especially in patients with clinical or laboratory features of adrenal insufficiency. Most of these cases are highly aggressive tumors and should be treated with multiagent chemotherapy. The role of bilateral adrenalectomy and/or radiotherapy cannot be estimated. Our patient with PAL was an 80-year-old man who presented with clinical and laboratory features of adrenal insufficiency. Combination chemotherapy plus rituximab was unsuccessful and our patient died from progressive disease.

Extracorporeal photopheresis in combination with bexarotene in the treatment of mycosis fungoides and Sézary syndrome

were histologically compatible with MDE. Elastica staining showed band-like and sharply demarcated elastolysis in the upper reticular dermis with conservation of the fine vertically orientated elastic fibres of the papillary dermis. In addition, focal areas of fragmented and absent elastic fibres were observed in the mid-reticular dermis (Fig. 2c). Only a scant perivascular lymphohistiocytic infiltrate was seen in the upper dermis. On closer examination, isolated and small clusters of CD68 (PGM1)-positive multinucleated giant cells were detected in the mid-reticular dermis showing elastophagocytosis. This case documents the transition of AEGCG into a noninflammatory end stage, clinically and histologically compatible with MDE. The pathogenesis of MDE is still unknown. Exposure to natural or artificial UV radiation frequently precedes the onset of MDE suggesting a pathogenic UV-mediated immunological mechanism. However, MDE lesions are not usually confined to sun-exposed areas, so that other cofactors are likely to play a role. Extensive sun exposure was denied by our patient. An association of MDE with nicotine abuse and oral contraceptives as in our case has repeatedly been reported. It is still unclear if this is mere coincidence or if these substances represent relevant trigger factors. MDE has been described after resolution of urticaria, erythematous skin changes and lesions resembling granuloma annulare. In the majority of cases, however, MDE develops without a clinically obvious inflammatory prodromal stage. The clinical course in our patient suggests that AEGCG and MDE might represent different stages in the clinical spectrum of dermal elastolysis. After the inflammatory prodromal stage of AEGCG and phagocytosis of elastic fibres by multinucleate giant cells the noninflammatory ‘burned-out’ end stage of MDE could result in a loss of elastic fibres in the mid-dermis. As elastophagocytosis by macrophages is, to a much lesser extent, also a feature of early inflammatory MDE lesions, AEGCG might represent a severe inflammatory variant of the same entity.

Dexamethasone, rituximab, and cyclophosphamide as primary treatment of Waldenstrom macroglobulinemia: final analysis of a phase 2 study.

To the editor: Reports of long-term outcomes of therapies in Waldenstrom macroglobulinemia (WM) are particularly important given the protracted course of the disease. In a large phase 2 study in 72 patients, using contemporary criteria for diagnosis and initiation of therapy,[1][1],[2][2] primary

Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.

Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation

The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen®) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkins lymphoma (NHL), 79 with Hodgkins lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.

Antiphospholipid syndrome: a predisposing factor for early onset HELLP syndrome

Hemolysis elevated liver enzymes low platelets syndrome (HELLP) is a relatively rare pregnancy-related thrombotic microangiopathic disorder, usually observed during the third trimester. Its incidence seems to be increased in patients with antiphospholipid syndrome (APS). In this report, we describe a 33-year-old pregnant woman with previously known primary APS who developed early onset HELLP syndrome during the 15th week of gestation. We also review the literature about this interesting relationship between APS and HELLP.

Keratinocyte growth factor is effective in the prevention of intestinal mucositis in patients with hematological malignancies treated with high-dose chemotherapy and autologous hematopoietic SCT: a video-capsule endoscopy study.

Oral and/or intestinal mucositis is a severe complication of hematopoietic SCT. Keratinocyte growth factor (KGF) has proven activity in the prevention of oral mucositis. We examined the efficacy of KGF in the prevention of intestinal mucositis. From January 2006 until December 2007, 35 consecutive patients underwent autologous SCT (auto-SCT) in our institution. A total of 15 consecutive patients who underwent auto-SCT from March 2007 to December 2007 received KGF for the prevention of mucositis and were included in the study group A, whereas 20 consecutive patients treated from January 2006 to March 2007, were included in the historical control group B. Oral and intestinal mucositis were significantly less severe in group A (P=0.002 and P<0.001, respectively). These results were confirmed with the use of video-capsule endoscopy. Patients in group A had a significantly lower incidence of neutropenic fever (P=0.026). Severe intestinal mucositis was significantly associated with a higher incidence of documented infections too (P=0.019). KGF is effective in the prevention of intestinal mucositis in patients undergoing auto-SCT. Patients with severe intestinal mucositis run a higher risk to develop infections.

Update on the mechanism of action and on clinical efficacy of extracorporeal photopheresis in the treatment of acute and chronic graft versus host disease in children.

Extracorporeal photopheresis (ECP) has been used for treatment of steroid-refractory graft versus host disease (GVHD) with encouraging results. Although its exact mechanism of action is not fully understood, photoapheresed cells seem to induce a selective immune response directed against alloreactive T cell populations without causing generalized immunosuppression. Current pediatric experience with ECP for GVHD is available in the form of a few retrospective small studies concerning children with steroid refractory GVHD. Reviewing these data we conclude that ECP is a safe procedure, well tolerated even in low-weight pediatric patients, which warrants further evaluation in well-designed, prospective, controlled studies.

Outcomes of Hodgkin’s Lymphoma Patients with Relapse or Progression following Autologous Hematopoietic Cell Transplantation

Patients with relapsed/progressed Hodgkins lymphoma (HL) following autologous hematopoietic cell transplantation (AHCT) may not have an invariably dismal outcome as previously considered. In a multicenter retrospective study, we evaluated 126 patients who relapsed/progressed after a median of 5 (1-132) months post first AHCT. Management consisted of irradiation, chemotherapy ± irradiation, second HCT, or palliation. Currently, 53 of 126 (42%) patients are alive for a median of 32 months since relapse/progression and 44 (35%) of them remain progression-free. Interval of <12 months to relapse/progression, presence of B-symptoms, and disease refractoriness at first AHCT failure adversely influenced overall survival (P < .05). The type of treatment had no impact on survival. Furthermore, to predict the outcome at the time of relapse/progression, we constructed a prognostic model based on 3 factors: interval of <12 months from first AHCT to relapse/progression, presence of B-symptoms, and pre-AHCT disease refractoriness. Patients with 0 to 1 factors achieved a median survival of 70 months compared to 17 months only in those with 2 to 3 factors (P < .001). This study, the largest reported to date, suggests that selected patients with relapse/progression after first AHCT can be rescued with current treatment modalities. However, relapsed/progressed HL following AHCT still poses a therapeutic challenge, and prospective trials are needed to determine the most appropriate approach in this setting.