A Schulenburg

Long-term outcome and quality of life of patients who are alive and in complete remission more than two years after allogeneic and syngeneic stem cell transplantation.

We assessed long-term outcome in 155 patients who had undergone an allogeneic/syngeneic stem cell transplant (SCT) and were in complete remission for more than 2 years after transplant. Probability of late transplant-related mortality was 6%, and affected only patients with chronic graft-versus-host disease (cGVHD). Thirteen percent of patients experienced relapse. Overall survival projected at 10 and 15 years was 83% and 76%, respectively. Secondary malignancies occurred in two patients, 7.5 and 11 years after SCT. Three female and four male patients parented children 19 to 84 months after SCT. Quality of life (QoL) was assessed in a cross-sectional study by the means of a 30-item questionnaire (QLQ-C30) of the EORTC. The questionnaire was sent to 127 patients remaining alive and answered by 106 patients. Seventy-three percent reported a good to very good QoL within 5 years after SCT and 78% after this time point. However, patients with cGVHD had significant impairment of physical, role and social functioning and only 60% of them were fit for work. These results from long-term survivors show that high cure rates with good to very good QoL can be achieved by allogeneic or syngeneic SCT.

Early and late gastrointestinal complications after myeloablative and nonmyeloablative allogeneic stem cell transplantation

Upper and lower gastrointestinal symptoms are major and serious complications after stem cell transplantation. Their main causes are gastrointestinal graft-versus-host disease (GVHD), infections, toxicity, or preexisting gastrointestinal diseases. The clinical presentation of each disease is nonspecific. The diagnostic procedure for this study included physical exam, stool cultures, endoscopy with biopsies, and abdominal computed tomography (CT). The study was designed prospectively with consecutive patients and performed at our institution in a clinical stem cell transplantation setting. Between January 1996 and September 2001, we analyzed 42 consecutive patients who had been admitted at our institution for gastrointestinal complaints after allogeneic stem cell transplantation for hematologic diseases. Diagnostic procedures revealed in decreasing order: GVHD (62%), gastritis/esophagitis (19%), cytomegalovirus (CMV) enteritis (11%), bacterial enteritis (6%), and toxic mucosal damage (2%). CT showed unspecific findings. Gastrointestinal GVHD and infectious colitis accounted for the majority of gastrointestinal complications after allogeneic stem cell transplantation in our patient population. The diagnosis was mainly based on endoscopically obtained biopsies.

Leukemia-free survival and mortality in patients with refractory or relapsed acute leukemia given marrow transplants from sibling and unrelated donors.

Between April 1982 and February 1997 39 patients (24 male, 15 female) with refractory acute leukemia and a median age of 31 years (19–51 years) received allogeneic marrow grafts from an HLA-identical sibling (n = 27), HLA-identical unrelated donor (MUD; n = 10) or 1-antigen mismatched unrelated donor (n = 2). Twenty-eight patients had acute myelogenous leukemia and 11 acute lymphoblastic leukemia. For conditioning most patients received total body irradiation combined with cyclophosphamide (n = 23) or etoposide (n = 7). For graft-versus-host disease prophylaxis patients received cyclosporin A (CsA) and methotrexate (MTX) (n = 20), MTX alone (n = 3), CsA and methylprednisone (n = 6), or CsA alone (n = 10), respectively. As of June 1997 probability of leukemia-free survival projected to 3 years after BMT was 14% for patients given sibling marrow grafts and 28% after MUD transplantation. Transplant-related mortality projected to 3 years was 32% after sibling and 37% after MUD marrow grafting. Although not significantly different, probability of relapse projected to 3 years after BMT was lower after MUD at 56% compared to 78% with sibling BMT. Thus, high-dose chemo/radiotherapy followed by allogeneic marrow infusion has a curative potential for patients with refractory leukemia and offers the chance of long-term disease-free survival for some patients.

CMV monitoring after peripheral blood stem cell and bone marrow transplantation by pp65 antigen and quantitative PCR

We prospectively monitored 74 consecutive allogeneic and 50 autologous patients after bone marrow/stem cell transplantation from May 1999 to October 2000 at our institution with quantitative CMV PCR and pp65 antigen assay once weekly from conditioning therapy to days 120 and 80 after transplantation, respectively. Written informed consent was obtained from every patient. CMV prophylaxis consisted of acyclovir during transplant. Additionally all patients received only platelet products from CMV-negative donors. In the case of CMV infection preemptive therapy with gancyclovir was applied. In the case of CMV disease high-dose immunoglobulin was given as well. In the allogeneic setting 16 out of 74 (22%) patients developed a positive PCR. Seven episodes of a positive pp65 antigen assay occurred in six allograft recipients. In the autologous setting no positive assay was found during the whole observation period. Additionally, in 6/16 patients a lymphoproliferative assay was performed during CMV infection. Two patients showed a positive (15 and 5.4) and four a negative (2,1.6,1,1.8) stimulation index. Bone Marrow Transplantation (2001) 28, 765–768.

Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia

Abstract Between January 1983 and December 1997, 88 patients (36 female, 52 male, median age 37 years, range 19–57) with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) at the University Hospital of Vienna. Sixty patients were in chronic phase, 18 in accelerated phase, and ten in blast crisis. Marrow donors were HLA-identical siblings for 64 patients (BM 58, PBSC 6), 2-antigen-mismatched related donors (RD) for two, HLA-identical unrelated donors (URD) for 17, and 1-antigen-mismatched URD for five. The median time from diagnosis to BMT was 22 months (range 2–91), and 63 patients had received prior interferon (IFN)-alpha therapy, 46 (73%) for more than 6 months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation (TBI) in 71 patients and CY and busulfan (BU) in 16. One patient received etoposide and TBI. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) was given to 12 patients, MTX and cyclosporin A (CSA) to 67, CSA alone to four, and CSA and methylprednisolone to five. Durable engraftment was documented in 80 of 82 patients (98%). As of December 31, 1997, 52 patients (59%) were alive, 38 (58%) after sibling transplantation with a median observation time of 73 months and 14 (64%) after URD transplantation with a median observation time of 12 months. Probability of overall survival is 59%, for patients undergoing transplantation in chronic phase and 44% for patients undergoing transplantation in advanced stage CML. Probability of disease-free survival (DFS) after sibling and URD BMT is 55% and 59%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 32% both after RD and after URD transplantation. Acute GVHD occurred in 53 of 80 evaluable patients (66%), consisting of grade III or IV in 14 patients (18%). Chronic GVHD developed in 40 of 63 eligible patients (63%), including extensive disease in 26 patients (41%). Thus, sibling and URD BMT offer high cure rates with acceptable toxicity to patients with CML.

Pneumocystis cystoides intestinalis with pneumoperitoneum and pneumoretroperitoneum in a patient with extensive chronic graft-versus-host disease

Pneumatosis cystoides intestinalis is a rare finding of intramural gasfilled cysts in the bowel wall and sometimes free air in the abdomen. A few conditions are reported to cause this disease, one of them being immunosuppression. We describe a 50-year-old Caucasian male with extensive chronic graft-versus-host disease (GVHD) of the gut and skin who developed PCI with pneumoperitoneum and pneumoretroperitoneum. To our knowledge, this is the first report of PCI occurring in a patient with active chronic GVHD which resolved spontaneously.

Routine fluoroscopic guidance is not required for placement of Hickman catheters via the supraclavicular route

The purpose of this study was to evaluate the efficacy and safety in placement of Hickman catheters via the supraclavicular route without fluoroscopic guidance. We studied 81 consecutive percutaneous placements of dual lumen Hickman catheters via the supraclavicular route without the use of fluoroscopic guidance. Success rates, technical problems, complications, infections and reasons for explantation were recorded prospectively. Seventy-nine punctures were successful (97.5%). One pneumothorax (1.2%) and three accidental arterial punctures (3.7%) occurred. Difficulties in introducing the catheter through the peel away sheath or misplacement were not observed. The catheters remained in place for a total of 7657 days (mean 94.5, range 3–392 days). Sixteen blood cultures were positive (2.1/1000 catheter days). Five catheters (6.1%) were lost because of mechanical complications. Forty-two lines (52%) were removed electively, 23 (28.4%) because of suspected infection, and two (2.5%) because of tunnel infection. Nine patients died with a functioning catheter. We conclude that the supraclavicular approach to the subclavian vein is safe and efficient for introduction of Hickman catheters. Using this access, routine fluoroscopic or sonographic guidance is not required for proper placement. Implantation of the lines in an intensive care unit did not lead to higher infection rates than those reported in the literature.

Cyclosporin A-induced ocular flutter after marrow transplantation

Ocular flutter is a rare neurologic condition occurring in patients suffering from viral encephalitis, intracranial neoplasia, paraneoplastic syndrome or intoxications. Neurotoxicity is a recognized complication of cyclosporin A (CsA) therapy, but ocular flutter has not been reported in association with CsA administration to date. We describe a 17-year-old female patient who developed ocular flutter 51 days after transplantation with marrow from an unrelated donor, for acute myeloid leukemia. After discontinuation of cyclosporin, which was given for prophylaxis of graft-versus-host disease, the clinical symptoms resolved within 3 weeks, but a slightly abnormal electrooculogram persisted for more than 10 months.

Gastrointestinal perforation early after peripheral blood stem cell transplantation for AL amyloidosis.

The morbidity and mortality of AL amyloidosis is caused by the deposition of Ig light chains as amyloid protein in vital organs. With conventional therapy median survival of patients with AL amyloidosis is 10–14 months. With high-dose chemotherapy clinical remissions of organ-specific disease have been reported. Here, we present a patient with high-risk AL amyloidosis who was given high-dose therapy and a peri- pheral blood stem cell transplant. Four days later she died of gastrointestinal perforation due to amyloid infiltrations.

Immunologic recovery of patients given CD34-selected peripheral blood progenitor cell transplantation for malignant diseases

Immunologic recovery of patients given CD34-selected peripheral blood progenitor cell transplantation for malignant diseases