Dietmar Söhngen

Treatment of relapsed idiopathic thrombocytopenic purpura with the anti‐CD20 monoclonal antibody rituximab: a pilot study

Abstract: We performed a prospective pilot study on 12 patients to evaluate the efficacy of the anti‐CD20 monoclonal antibody rituximab in relapsed idiopathic thrombocytopenic purpura (ITP). Inclusion criteria were relapse of ITP with a thrombocyte count <20 000 µL−1 and unsuccessful corticosteroid treatment. Eleven patients had a previous splenectomy, five patients had unsuccessful cytotoxic treatment, and six patients were refractory to intravenous immunoglobulins before rituximab therapy. Response criteria were as follows. Complete remission (CR): normalization of thrombocyte count for at least 30 d. Partial remission (PR): an increase of thrombocytes to above 30 000 µL−1 for at least 30 d. Minor response (MR): any increase above 30 000 µL−1 for less than 30 d but more than 10 d. No response (NR): failure to achieve any of the above responses. Treatment plan: We administered 375 mg m−2 of rituximab once weekly on up to four consecutive weeks, unless there was early CR. Five patients (41%) achieved CR, two patients (17%) PR, and two patients MR (overall response rate 75%, median follow‐up of responders 320 d). Four CR patients are ongoing; one CR patient relapsed after 6 months. Adverse events included excessive thrombocytosis in one patient as well as minor infusion‐related (grade I) toxicities in four patients. We conclude that rituximab is a promising agent in the treatment of relapsed ITP.

Using at least 5x10(6)/kg CD34+ cells for autologous stem cell transplantation significantly reduces febrile complications and use of antibiotics after transplantation.

For autologous stem cell transplantation, it is common practice to infuse at least 2 × 106/kg CD34+ cells to ensure rapid engraftment. However it was recently claimed that increasing the threshold to 5×106/kg leads to a faster platelet engraftment. To evaluate these threshold values in our patient population we undertook a retrospective analysis of 127 autologous transplants performed at our institution between 1992 and 1998. Diagnoses included Hodgkin’s and non-Hodgkin’s lymphoma, myeloma, acute leukaemias and solid tumours. The transplant was peripheral blood stem cells in 107 cases and CD34-selected peripheral blood stem cells in 20 cases. The median number of transplanted CD34+ cells was 3.2 × 106/kg (range 0.64–25.9 × 106/kg) Haematopoietic recovery to a neutrophil count >0.5 × 109/l took a median of 10 (range 5–16) days from transplant. When comparing patients receiving at least 5 × 106/kg and 2–5 × 106/kg CD34+ cells we found a significant reduction in the median number of days with fever (1 vs 3.5 days, P = 0.0025), incidence of fever (78.8 vs 92.1%, P = 0.032) as well as duration of antibiotic treatment (7 vs 10 days, P = 0.038). This was paralleled by a faster neutrophil recovery to 0.5 × 109/l (9 vs 10 days, P = 0.047). There was no significant difference in the number of platelet or red cell transfusions between the two groups. We conclude that transplantation with a stem cell dose of at least 5 × 106/kg CD34+ cells reduces infectious complications and should thereby increase the safety of this type of therapy while reducing duration (and cost) of antibiotic therapy. The transplantation threshold should thus not remain at 2 × 106/kg par- ticularly in patients with a good stem cell mobilisation capacity.

Successful peripheral blood stem cell mobilization with etoposide (VP- 16) in patients with relapsed or resistant lymphoma who failed cyclophosphamide mobilization

High-dose chemotherapy (HDCT) followed by autologous blood stem cell transplantation is considered the treatment of choice for patients with relapsed or resistant aggressive non-Hodgkin’s lymphoma (NHL) or Hodgkin’s disease (HD). However, several authors report failure of standard mobilization regimens in 29% to 56% of these patients making the completion of HDCT impossible and as a result, negatively influencing long-term outcome. Thus, effective new regimens for patients failing initial mobilization are needed. Here we report the results of using etoposide as a mobilizing agent in 16 patients with primary resistant or relapsed malignant lymphoma who had failed prior mobilization of peripheral blood stem cells (PBSC) with cyclophosphamide (4 g/m2) followed by G-CSF. The use of etoposide 500 mg/m2 (days 1–4) + G-CSF resulted in the successful collection of adequate numbers of PBSC with a median harvest of 3.6 × 106/kg (range 2.2–12.6) CD34+ cells in all 16 patients. In 7/16 (44%) patients, the target yield of at least 2.0 × 106CD34+ cells was harvested by a single apheresis and the maximum number of separations for all patients was two. No excessive toxicities appeared, allowing all patients to proceed to myeloablative chemotherapy. In addition, median peak values of circulating CD34+cells were significantly higher after etoposide as compared to cyclophosphamide (49.2/μl vs4.7/μl; P = 0.0004). These results indicate that etoposide + G-CSF is a highly effective mobilization regimen in patients who have failed cyclophosphamide mobilization.

A case of thrombotic thrombocytopenic purpura in an adult treated with vincristine.

Abstract The case of a woman with thrombotic thrombocytopenic purpura refractory to prolonged treatment with plasma exchange and steroid treatment is described. The addition of vincristine yielded a complete response, which has been maintained for 9 months up to the time of this report.

High platelet contamination in progenitor cell concentrates results in significantly lower CD34+ yield after immunoselection.

BACKGROUND: Selection of CD34+ cells by specific immunoselection leads to a significant loss of those cells. The factors influencing the yield and purity are not well identified. The results of CD34+ selection from peripheral blood progenitor cells (PBPCs) with high and low platelet contamination that are harvested with two different cell separators are reported.

Fatal thrombotic thrombocytopenic purpura as a rare complication following allogeneic stem cell transplantation

Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare disease which, together with hemolytic uremic syndrome, is subsumed under thrombotic microangiopathy. After stem cell transplantation (SCT), this syndrome represents a possibly fatal complication with a higher incidence in allogeneic SCT than in autologous SCT. Although plasmapheresis offers an encouraging treatment modality in classic TTP, this seems less effective in bone marrow transplant-associated microangiopathy. This is probably due to a different etiology. We present a case of transplant-associated TTP with a fatal outcome despite multiple courses of plasmapheresis.

Association of HSV reactivation and pro-inflammatory cytokine levels with the severity of stomatitis after BEAM chemotherapy and autologous SCT

BackgroundStomatitis, including oral mucositis and ulcerations induced by HSV-reactivation are major sources of morbidity after high-dose (HD) chemotherapy and subsequent autologous hematopoietic stem cell transplantation (SCT). While increased synthesis of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α)—as well as reactivation of viral infections have frequently been observed in this setting, data on their association with the severity of mucositis is limited.Materials and methodsFifteen patients with Hodgkins or non–Hodgkins lymphoma receiving HD conditioning chemotherapy and autologous SCT were assessed with respect to oral pain and severity of stomatitis on day –6, 0, +5 to +7, +13 to +15, and +100. On the same dates, IL-1 and TNF-α were quantified in saliva and screening for a wide range of viral pathogens was carried out by cell culture and PCR and complemented by serological analyses. t Tests were used to assess potential associations between these variables.ResultsAll but one patient had a positive HSV IgG titer at baseline. Reactivation as confirmed by HSV PCR was observed in seven patients (50%). There was a significant association between the presence of HSV in saliva samples and severity of stomatitis (t test, p = 0.015). The highest concentration of TNF-α and IL-1 coincided with the maximum intensity of stomatitis, but the association was not significant.ConclusionWe found a significant association between the presence of HSV in saliva samples and severity of stomatitis in patients receiving HD chemotherapy and subsequent autologous SCT. While acyclovir prophylaxis has become standard for patients undergoing allogeneic SCT, this issue has not been sufficiently explored for other chemotherapy regimens. Based on our findings, conduction of a well-powered controlled randomized trial may be warranted.

Trimethoprim/sulfamethoxazole prophylaxis impairs function of mobilised autologous peripheral blood stem cells

Trimethoprim/sulfamethoxazole prophylaxis impairs function of mobilised autologous peripheral blood stem cells

Failure of anti-infective mouth rinses and concomitant antibiotic prophylaxis to decrease oral mucosal colonization in autologous stem cell transplantation

Summary:Autologous stem cell transplantation has augmented treatment successes. However, high-dose chemotherapy is still accompanied by dose-limiting toxicities, for example, severe mucositis. Mucosal lesions serve as portals of entry for infections. In order to reduce the oral microbial burden, we prospectively evaluated the microbiological impact of a complex regimen of mouth rinses consisting of concomitantly applied polyene antifungals, povidone-iodine, chlorhexidine, sage tea, and prophylactic ciprofloxacin and fluconazole. A total of 15 patients were enrolled into this longitudinal evaluation. Colony-forming units (CFU) were quantitated from saliva, buccal and palatinal swabs during high-dose chemotherapy and autologous stem cell transplantation. The number of CFU did not show any significant changes after initiation of the mouth rinses and the prophylactic antibiotics. The median CFU count was 268 × 106/ml saliva before chemotherapy and decreased after initiation of intravenous antibiotics only. Neither prophylactic nor therapeutic antifungals significantly reduced the number of cultures positive for yeasts. Since 90% of our patients had febrile neutropenia at some time point during the observation period, the approach evaluated cannot be recommended as prophylaxis of febrile neutropenia as such.

Congenital dyserythropoietic anemia type III associated with congenital atrioseptal defect has led to severe cardiac problems in a 32‐year‐old patient

We report the case of a 32‐year‐old woman who was admitted at hospital because of ortho‐dyspnea, arrhythmia, and paleness. Clinical examination showed continuous arrhythmia, systolic heart murmur, enlargement of spleen and liver, and pathologic hematological parameters, thus indicating an intravasal hemolysis (elevated HBDH, bilirubin, and reticulocytes; reduced hemoglobin and haptoglobin levels), and bone‐marrow‐smears showed a typical cytomorphology of CDA III. The patients diagnosis was heart failure caused by mitral valve insufficiency due to congenital atrioseptal defect associated with congenital dyserythropoietic anemia type III (CDA III). Am. J. Hematol 64:314–316, 2000.