melphalan and Postoperative-Complications

Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 35% of the patients, with the liver being the most common site for metastases. These metastases are generally refractory to systemic chemotherapy, and the median survival for patients with liver metastases is about 6 months. This phase II trial reports the experience of isolated hepatic perfusion (IHP) as a treatment option.. A total of 34 patients with isolated liver metastasis from ocular melanoma underwent IHP. An overall survival comparison was made using data retrieved from the National Patient Register managed by the Swedish National Board of Health and Welfare.. An overall radiological response was seen in 68% of the patients, with 12% having a complete response. Time to local progression was 7 months; 68% of the patients developed extrahepatic metastases after a median of 13 months, and the median overall survival was 24 months. There was a significant survival advantage of 14 months (p = 0.029) when comparing these patients with a control group consisting of the longest surviving patients in Sweden with uveal melanoma liver metastases not treated with IHP.. IHP is a treatment option with a high response rate and a potential survival benefit of more than 1 year. IHP should be considered an option in the treatment of uveal melanoma metastases. A randomized trial comparing IHP and best alternative care will start during 2013 (the SCANDIUM trial, ClinicalTrials.gov identifier NCT01785316).

Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Disease Progression; Eye Neoplasms; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Staging; Perfusion; Postoperative Complications; Prognosis; Registries; Survival Rate; Sweden; Young Adult

With the eventual goal of reducing relapse and thus improving overall survival in selected lymphoma patients, a Phase I study was performed using the cytoprotectant amifostine to permit safe dose-augmentation of melphalan in the carmustine (BCNU), etoposide, cytarabine (arabinosylcytosine), and melphalan (BEAM) regimen before autologous hematopoietic stem cell transplantation. Between 30 July 2003 and 25 November 2008, a total of 32 lymphoma patients were entered, of which 28 were evaluable. We found the melphalan dose in BEAM could be safely escalated to at least 260 mg/m², a substantial increase from the usual dose of 140 mg/m² in BEAM while the trial was terminated early due to poor accrual, no maximal tolerated dose or dose-limiting toxicity was found. A Phase II trial is planned.

Topics: Adult; Aged; Amifostine; Antineoplastic Combined Chemotherapy Protocols; Atrial Fibrillation; Carmustine; Combined Modality Therapy; Cytarabine; Cytoprotection; Dose-Response Relationship, Drug; Etoposide; Female; Humans; Lymphoma; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Mucositis; Pancytopenia; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Transplantation Conditioning; Transplantation, Autologous; Young Adult

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare, fatal autoimmune disorder caused by mutations in the FOXP3 gene leading to the disruption of signaling pathways involved in regulatory T-lymphocyte function. Lifelong multiagent immunosuppression is necessary to control debilitating autoimmune manifestations such as colitis and food allergies. Allogeneic hematopoietic stem cell transplantation (HSCT) can restore T-cell regulatory function but has been previously associated with poor outcome. We describe successful HSCT in 4 patients with IPEX syndrome using a novel reduced-intensity conditioning regimen that resulted in stable donor engraftment, reconstitution of FOXP3+ T regulatory CD4+ cells, and amelioration of gastrointestinal symptoms.

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Bone Marrow Transplantation; Child; Child, Preschool; Colitis; Endocrine System Diseases; Food Hypersensitivity; Forkhead Transcription Factors; Genes, X-Linked; Graft Survival; Humans; Ichthyosis, X-Linked; Immunologic Deficiency Syndromes; Infant; Leukocyte Count; Melphalan; Postoperative Complications; Reoperation; Syndrome; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

Sixteen patients with stage III multiple myeloma (MM) and a median age of 51 years were treated with autografting followed by reduced intensity conditioning allotransplantation (RICT). Nine patients are alive in remission at a median of 30 months after their transplants, one patient is alive in relapse and 6 patients died of progressive disease (5) or extensive chronic graft-versus-host disease, infections and progressive disease (1). We suggest that this two-step approach is feasible and it has strong anti-myeloma activity.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Disease-Free Survival; Feasibility Studies; Female; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Infections; Male; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Remission Induction; Salvage Therapy; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Vidarabine; Whole-Body Irradiation

Thirty-one patients with resistant Hodgkin's disease were treated by an identical high dose chemotherapy regimen and autologous bone marrow transplantation. Twelve of these patients received recombinant human granulocyte/macrophage colony stimulating factor (rh GM-CSF) in a phase I/II study. rh GM-CSF was administered by continuous infusion into an indwelling central venous catheter for 3-21 days at doses of 100-400 micrograms/m2/day. The patients receiving rh GM-CSF did not differ significantly from those who did not receive growth factor with regard to age, previous therapy or number of bone marrow cells infused. rh GM-CSF resulted in more rapid neutrophil regeneration, the average time to achieve a neutrophil count of greater than or equal to 0.5 x 10(9)/l being 17.5 days compared to 24.9 days in the control group (p less than 0.01). Platelet recovery was very varied and not accelerated by rh GM-CSF. Patients receiving rh GM-CSF had a similar infection rate (58% vs 68% in the control group), similar number of febrile days (5.0 vs 4.7 days) and similar period of hospitalization to the control group (30.1 vs 30.2 days). Randomized controlled trials are now required to define the clinical value of rh GM-CSF in the setting of autologous bone marrow transplantation.

Topics: Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Colony-Stimulating Factors; Combined Modality Therapy; Cytarabine; Drug Evaluation; Etoposide; Granulocytes; Hodgkin Disease; Humans; Leukocyte Count; Macrophages; Melphalan; Neutropenia; Neutrophils; Postoperative Complications; Recombinant Proteins; Transplantation, Autologous

The conventional conditioning regimen for patients with leukemia prior to allogeneic stem cell transplantation is myeloablation to eradicate residual leukemic cells and host immunocompetent cells. This helps prevent leukemic relapse as well as rejection after transplantation. A myeloablative conditioning regimen with busulfan (BU) or total body irradiation (TBI) is effective for eradication of leukemic cells but is also associated with significant toxicities in the acute or late phase in pediatric patients. In an effort to minimize these adverse effects, we conducted bone marrow transplantation (BMT) from unrelated volunteer donors using a conditioning regimen without BU or TBI.. Ten patients with acute leukemia in first or second remission were given a "non-BU, non-TBI conditioning regimen," which consisted of fludarabine (FLU), cytarabine (CA), and melphalan (L-PAM) after FLAG combined with L-PAM.. Engraftment was obtained in all patients, and two patients died of relapse. Eight of 10 patients have been disease-free for a median of 126 months (116-142) after transplantation. The overall survival, event-free survival, relapse rate, and treatment-related mortality were 80.0%, 80.0%, 20.0% and 0.0%, respectively. In female patients, spontaneous menstruation with normal luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E2) levels was observed in all four patients at post-pubertal age.. This conditioning regimen of FLAG combined with L-PAM (which did not contain BU and TBI) was associated with good outcomes and minimal late adverse effects in children with acute leukemia who have undergone allogeneic BMT from unrelated volunteer donors.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Busulfan; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Female; Follow-Up Studies; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Humans; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Male; Melphalan; Neoplasm Recurrence, Local; Postoperative Complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Remission Induction; Survival Rate; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Whole-Body Irradiation

The following case shows corneal crystal formation in a patient in whom thee systemic work-up led to the diagnosis of a monoclonal gammopathy with increased monoclonal immunoglobulin G (IgG). We present the corneal signs and subsequent haematological investigations undertaken to establish this important association.. Systemic work-up of a patient with corneal deposits showed a monoclonal gammopathy with increased monoclonal immunoglobulin (IgG-type kappa). Corneal crystals, a rare, but significant, clinical finding, may be the initial presentation in a patient with monoclonal gammopathy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bence Jones Protein; Combined Modality Therapy; Corneal Opacity; Crystallization; Cyclophosphamide; Diagnosis, Differential; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin kappa-Chains; Kidney Failure, Chronic; Lenalidomide; Male; Melphalan; Middle Aged; Paraproteinemias; Paraproteins; Phacoemulsification; Postoperative Complications; Prednisone; Slit Lamp; Thalidomide

Immunoglobulin light chain (AL) amyloidosis can be treated with high-dose melphalan and autologous stem cell transplantation (HDM/SCT). Risk factors for infections may include hyposplenism, hypogammaglobulinemia, treatment-related neutropenia, melphalan-induced mucositis, and nosocomial exposures.. A review of 493 patients with AL amyloidosis undergoing treatment with HDM/SCT from August 1994 to August 2009 was performed. The objectives were to determine the rate and types of infections following HDM/SCT, to identify factors associated with microbiologically documented infections, and to assess the contribution of infections to all-cause treatment-related mortality (TRM; defined as deaths within 100 days of SCT).. Microbiologically documented infections after HDM/SCT occurred in 24% (n = 119) of patients. TRM was 10% (n = 48) overall, and 21% (n = 25) in patients who had a documented infection. Thus, the relative risk of TRM in a patient with a documented infection was 3.42 (95% confidence interval [CI] 2.02-5.79). Infections were caused by gram-positive bacteria in 51%, anaerobic bacteria in 16%, gram-negative bacteria in 13%, and fungi in 9% of cases. Serum creatinine >2 mg/dL was associated with increased risk of post-SCT infection (38% vs. 21%, P = 0.0007) with an odds ratio of 2.27 (95% CI 1.40-3.68). No significant association for infection was found for age, gender, cardiac involvement, prior steroid therapy, dose of melphalan, multiorgan involvement, days to neutrophil engraftment, or dose of CD34 +  cells infused.. Serum creatinine >2 mg/dL is a risk factor for infections in patients with AL amyloidosis undergoing HDM/SCT. The relative risk of TRM in a patient with a documented infection was increased >3-fold. A broad spectrum of infections, similar to that in other SCT patients, is seen in this population in the early post-SCT period.

Topics: Aged; Aged, 80 and over; Amyloidosis; Bacterial Infections; Combined Modality Therapy; Cross Infection; Dose-Response Relationship, Drug; Female; Humans; Immunoglobulin Light Chains; Male; Melphalan; Middle Aged; Mycoses; Myeloablative Agonists; Postoperative Complications; Risk Factors; Stem Cell Transplantation; Transplantation, Autologous

To investigate the safety of treatment with ophthalmic artery cannulation for intra-arterial chemotherapy (IAC) for children with intraocular retinoblastoma (RB).. In the RB Treatment Center of General Hospital of Armed Police Forces between January 2009 and September 2011, 42 patients who were diagnosed intraocular RB and treated with ophthalmic artery cannulation for IAC, 8 patients were treated 1 circle, 31 patients were treated 2 circles and 3 patients were treated 3 circles (total, 96 times). Each month had IAC once. The ophthalmic and the whole body evaluations were performed during IAC and after IAC for each circle, the blood cell count, alanine aminotransferase (ALT), serum creatinine (Scr), CK-MB content before and after IAC for 1 circle, 2 circles and 3 circles were determined.. (1) In 52 eyes of 42 patients, 44 eyes (84.6%) were in remission. (2) Successful IAC was achieved in all cases, no severe side effects occurred during IAC. (3) The main ophthalmic complications were eyelid edema and blepharoptosis after IAC, the incidence for 1 circle was 18% (2/11) and 9% (1/11); for 2 circles was 29% (11/38) and 21% (8/38); for 3 circles was all 100% (3/3). The rare complications were vitreous hemorrhage and heterotropia, the incidence was all 2% (1/42). The incidence of eyelid edema and blepharoptosis had no significant differences for 1 circle IAC compared with 2 circles (P > 0.05); the incidence of eyelid edema and blepharoptosis had significant differences for 3 circles IAC compared with 2 circles and 1 circle (P < 0.01). (4) No fever, septicemia and other systemic toxic effects occurred. (5) ALT of 19% patients (8/42) elevated temporarily and CK-MB of 24% patients (10/42) increased. The blood cell counts, ALT, Scr, and CK-MB content before IAC had no significant differences compared with that at 24 h after IAC for 1 circle, 2 circles and 3 circles (P > 0.05).. Ophthalmic artery cannulation for IAC is a safe and effective method in treating intraocular stage retinoblastoma.

Topics: Antineoplastic Agents, Alkylating; Catheterization; Child, Preschool; Female; Humans; Infant; Infusions, Intra-Arterial; Liver Function Tests; Male; Melphalan; Neoplasm Staging; Ophthalmic Artery; Postoperative Complications; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Treatment Outcome

After ilioinguinal radical lymph node dissection (RLND), the therapy for lymph fistulas constitutes a challenge. Risk factors for the genesis of lymph fistulas have not been sufficiently evaluated. We investigated possible factors that could influence the development of lymph fistulas in patients suffering from malignant melanoma after iloinguinal RLND.. The analysis was related to patients with intransit and lymphonodal metastasised malignant melanoma of the lower limb, who underwent RLND and isolated limb perfusion (ILP). Prospective data acquisition from patients undergoing ilioinguinal RLND and ILP in a one-step approach was performed. The association of lymph fistulas to risk factors was calculated using chi-squared, linear-by-linear test and ROC curves. As possible risk factors we investigated the presence of prior surgery and diabetes mellitus type II in the medical history, chemotherapeutics, patient age and the body mass index (BMI).. Postoperative lymph fistula occurred in 11 of 108 patients (10.2%). A significant association to lymph fistulas was found in BMI (30.2± 7.0 kg/m (2), p<0.02). Other parameters, such as prior surgery (82% vs. 71%), diabetes mellitus type II (9% vs. 11.7%), chemotherapeutics and patient age (mean 67.8 vs. 62.4 years) showed no influence.. Our results indicate that the incidence of lymph fistulas after RLND and ILP of malignant melanoma of the lower limb was associated with an increased BMI. Thus, for the prevention of lymph fistulae, an initially alternative wound-closure dressing like vacuum assisted closure (V.A.C.) dressing could be of clinical relevance for obese patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Female; Fistula; Humans; Inguinal Canal; Leg; Lymph Node Excision; Lymphatic Diseases; Male; Melanoma; Melphalan; Middle Aged; Negative-Pressure Wound Therapy; Neoplasm Staging; Obesity; Postoperative Complications; Retrospective Studies; Risk Factors; Skin Neoplasms; Tumor Burden; Tumor Necrosis Factor-alpha

We report on 12 patients with chronic granulomatous disease transplanted with hematopoietic stem cells from matched unrelated (n = 9) or matched sibling donors (n = 3). The most common infectious complication was pulmonary aspergillosis, which nine patients had previously developed. Only 5 of 12 individuals had normal lung function prior to transplantation. At a mean follow-up of 53 months 9 of the 12 patients are alive including 7 of 9 following matched unrelated donor (MUD) transplantation. One patient died from ARDS, another from systemic BK virus infection, the third from complications of chronic graft-versus-host disease. Seven of nine surviving patients have normal lung function now. HSCT from a MUD is an option worth considering when no matched family donor is available. Restricted lung function prior to HSCT does not appear to be a limiting factor for such treatment.

Topics: Adolescent; Busulfan; Child; Child, Preschool; Chimerism; Cyclophosphamide; Follow-Up Studies; Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Kaplan-Meier Estimate; Male; Melphalan; Postoperative Complications; Pulmonary Aspergillosis; Retrospective Studies; Treatment Outcome; Vidarabine; Young Adult

Topics: Acyclovir; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Carmustine; Cisplatin; Colitis; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Hematopoietic Stem Cell Transplantation; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Intestinal Pseudo-Obstruction; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Postoperative Complications; Prednisolone; Rituximab; Transplantation, Autologous; Vincristine; Virus Activation

We report a novel regimen for refractory post-transplant T-cell lymphoma (PTL). Our patient presented with non-Epstein-Barr virus (EBV) related, T-cell post-transplant lymphoproliferative disease (PTLD) 3.5 years after liver transplantation. Initially diagnosed as polyclonal PTLD, the disease progressed to a monoclonal, T-cell PTL that was refractory to several chemotherapy regimens but responded to a regimen consisting of fludarabine, cyclophosphamide, cytarabine, and alemtuzumab. Consolidation therapy included high-dose chemotherapy, autologous hematopoietic stem cell rescue, and radiation therapy. She remains in remission 2.5 years later. T-cell PTL is a rare disease with a poor prognosis; this regimen provides a novel, potentially curative approach for its treatment.

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biliary Atresia; Carboplatin; Carmustine; Cyclophosphamide; Cytarabine; Disease Progression; Doxorubicin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Lymphoma, T-Cell, Peripheral; Lymphoproliferative Disorders; Melphalan; Mesna; Postoperative Complications; Prednisone; Radiotherapy, Adjuvant; Transplantation, Autologous; Vidarabine; Vincristine

Allogeneic stem cell transplantation is the only curative treatment for Wiskott-Aldrich syndrome. The authors retrospectively analyzed the outcome with this procedure in 13 patients with severe Wiskott-Aldrich syndrome transplanted in 5 Spanish centers from 1989 to 2006. A patient was transplanted twice from the same donor due to a late engraftment failure. Age at transplant ranged from 7 to 192 months (median 30 months). There were 10 matched donors (3 related and 7 unrelated), 2 mismatched unrelated, and 1 haploidentical. Conditioning regimen consisted of busulfan and cyclophosphamide (BuCy) in 11 cases and fludarabine and melfalan (1) or BuCy (1). ATG was added in transplants from non-genetically matched donors. GvHD prophylaxis consisted of cyclosporine and methotrexate in most patients plus T-cell depletion in the haploidentical HSCT. Nine of the 13 transplanted patients are alive with complete clinical, immunologic, and hematologic recovery 8-204 months (median 101 months) after HSCT. Eight surviving patients had been transplanted from matched donors (3 related and 5 unrelated) and 1 from a haploidentical donor. Four patients died, 2 transplanted from matched donors (1 from acute GvHD and organ failure, 1 from a lymphoproliferative disorder after a second transplant), and 2 transplanted from mismatched unrelated donors (1 from acute GvHD and organ failure, 1 from graft failure and infection). Allogeneic hemopoietic stem cell transplantation must be utilized in all patients with severe Wisckott-Aldrich syndrome, using the most suitable graft variant for each patient.

Topics: Antilymphocyte Serum; Busulfan; Child; Child, Preschool; Cyclophosphamide; Cyclosporine; Graft vs Host Disease; Haplotypes; Hematopoietic Stem Cell Transplantation; Histocompatibility; HLA Antigens; Humans; Immunosuppressive Agents; Infant; Living Donors; Lymphocyte Depletion; Male; Melphalan; Multiple Organ Failure; Postoperative Complications; Reoperation; Retrospective Studies; Spain; T-Lymphocytes; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine; Wiskott-Aldrich Syndrome

To analyse results with a standardized HILP procedure in terms of response rate, recurrence pattern and complication rate.. From 1992 to 2003 HILP with melphalan and dactinomycin was performed in 101 patients with loco-regional metastases of malignant melanoma of the limbs. Among these were 66 women and 35 men with a median age of 62 years. Forty patients were in M. D. Anderson stage IIIA, 51 patients in stage IIIAB and 9 had stage IV disease at the time of perfusion. If not been done before, regional lymph node dissection preceded limb perfusion in the same setting.. A complete response (CR) was observed in 58 out of 87 evaluable patients. Twenty-one patients achieved a partial response (PR) and eight patients were non-responders. The overall response rate was 90.8%. The median recurrence-free interval after CR was 21 months. Severe toxicity (Wieberdink IV/V) was observed in five patients necessitating fasciotomy in four of them and above knee amputation in one patient. All further cases presented with grade II-III toxicity. The overall survival was 42 months, with a 5-year survival rate of 38%. Survival significantly differed according to stage of disease.. HILP is an effective treatment for loco-regional tumour relapse of malignant melanoma of the extremities and has improved by modification of technique. In the absence of regional lymph node and distant metastases long-term survival can be achieved in responders.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Dactinomycin; Extremities; Female; Humans; Hyperthermia, Induced; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Complications; Surgical Procedures, Operative; Survival Analysis; Treatment Outcome

A 52-year-old patient with atypical plasmocytoma presented with a bilateral serous detachment of the retina as well as a huge detachment of the pigment epithelium (PE) in the periphery. Shortly thereafter the PE ruptured. In the left eye this led to substantial central macular fibrosis.. The clinically healthy patient showed a nephrotic syndrome; neither typical monoclonality was detectable nor was erythropoiesis or myelopoiesis reduced.. To avoid further reduction of VA pars plana vitrectomy (ppV) with silicone oil tamponade and laser coagulation was performed. Clinical findings were reduced significantly and VA was stabilized for 2.5 years.. PE detachments and serous retinal detachments in patients with nephrotic syndrome are only mentioned in a few cases. However, a peripheral rupture of the PE to this extent seems to be very rare. Early ppV with silicone oil and laser coagulation may prevent further macular fibrosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Choroidal Neovascularization; Comorbidity; Female; Fluorescein Angiography; Follow-Up Studies; Humans; Kidney Neoplasms; Laser Coagulation; Lenses, Intraocular; Melphalan; Middle Aged; Nephrotic Syndrome; Ophthalmoscopy; Plasmacytoma; Postoperative Complications; Prednisolone; Recurrence; Renal Insufficiency; Reoperation; Retinal Detachment; Retinal Perforations; Silicone Oils; Visual Acuity; Vitrectomy

Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries after reduced intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, and imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to a report by Hogan et al (Blood. 2004;103:78-84). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease (CLD) related to GVHD or sepsis (n = 15), GVHD (n = 7), cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4 alanine aminotransferase elevation were comparable across the 3 types of hepatic injuries. Serum gamma-glutamil transpeptidase was not elevated in any patients with cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil transpeptidase elevation. Multivariate analysis identified 2 risk factors for hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant problems after RICBT, and that GVHD and blood stream infection contribute to their pathogenesis.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Busulfan; Chemical and Drug Induced Liver Injury; Cholangitis; Cord Blood Stem Cell Transplantation; Cyclosporine; Female; Hematologic Diseases; Hematologic Neoplasms; Hepatic Veno-Occlusive Disease; Humans; Hyperbilirubinemia; Immunosuppressive Agents; Incidence; Infant, Newborn; Liver Diseases; Liver Function Tests; Male; Melphalan; Middle Aged; Postoperative Complications; Risk Factors; Tacrolimus; Tissue Donors; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation

Reduced-intensity regimens (RIRs) are being used with increasing frequency in patients with non-Hodgkin's lymphoma (NHL) undergoing allogeneic transplantation. The impact of dose reduction on relapse and survival has not been extensively studied. We performed a retrospective analysis of 88 patients conditioned with conventional myeloablative regimens (CMRs) (n = 48) and an RIR (n = 40) of fludarabine 125 mg/m(2) and melphalan 140 mg/m(2). Compared with the patients receiving CMR, those receiving RIR were older, had more often failed autologous transplantation, and had more frequently received peripheral blood and unrelated donor transplants. Graft-versus-host disease prophylaxis was provided with cyclosporine + methotrexate +/- prednisone for the CMR and with cyclosporine + mycophenolate +/- methotrexate for the RIR. The relapse rate was significantly lower in the patients receiving CMR than in those receiving RIR (13% vs 28%; P = .05). The 1-year transplantation-related mortality rate was 33% for CMR and 28% for RIR (P = .40). Kaplan-Meier 2-year overall survival and progression-free survival were 52% and 46% for CMR versus 53% and 40% for RIR (P = not significant). Using cumulative incidence functions based on competing risks, univariate analysis, and treatment-related prognostic factors, we found that higher treatment intensity (P = .03; relative risk [RR] = 35%) and absence of previous autologous transplantation (P = .0007; RR = 20%) were associated with a lower relapse rate. Using a Cox univariate proportional hazards model, we found that chemosensitive disease at transplantation (P = .05; RR = 57%) and absence of previous autologous transplantation (P = .002; RR = 37%) were associated with improved survival. Our observation of similar survival in the patients receiving CMR and those receiving RIR confirms that RIRs are feasible alternatives for high-risk patients with NHL; however, the data suggest that reduced treatment intensity and previous autologous transplantation are associated with increased relapse.

Topics: Adolescent; Adult; Aged; Busulfan; Cause of Death; Cohort Studies; Cyclophosphamide; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Graft vs Host Disease; Hepatic Veno-Occlusive Disease; Humans; Infections; Kaplan-Meier Estimate; Lung Diseases, Interstitial; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Proportional Hazards Models; Reoperation; Retrospective Studies; Risk Factors; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine; Whole-Body Irradiation

Topics: Aged; Biopsy; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Drug Therapy, Combination; Glomerulonephritis, Membranoproliferative; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Melphalan; Paraproteinemias; Paraproteins; Plasmapheresis; Postoperative Complications; Prednisolone; Recurrence; Transplantation; Transplantation, Homologous

Primary systemic amyloidosis (AL) is a plasma cell dyscrasia characterized by the extracellular deposition of immunoglobulins light chains in different organs and systems. Median survival with current standard treatment is less than 2 years. Intensive chemotherapy followed by hematopoietic stem cell rescue has been used in AL for the last five years. The reported results are encouraging, with a high response rate (65%). Nonetheless, this procedure is associated to an important toxicity, with high transplant related mortality (about 25%). In patients with advanced AL (more than two involved organs) and/or complicated cardiac disease, the mortality is particularly high. In the current report we describe the outcome of the first five patients who received high dose therapy for AL at our institution.. This treatment was administered to patients up to the age of 70 years, who met the standard eligibility criteria for an autologous bone marrow transplantation. Intensive treatment consisted of melphalan 200 mg/m2 in all patients but one who received 140 mg/m2.. Two patients died during the first month after the transplant (arrhythmia: 1, multiorganic failure: 1). Both patients had a poor performance status and advanced disease, with more than two organs involved. The response in the remaining three was of stabilization of the nephrotic syndrome in one and objective response in all the involved organs in the remaining two.. High dose therapy (HDT) with stem cell rescue in AL produces a high response rate. Nevertheless, this treatment approach is associated to a high toxicity.

Topics: Adult; Aged; Amyloidosis; Antineoplastic Agents, Alkylating; Combined Modality Therapy; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Postoperative Complications; Time Factors

Effort angina due to left main trunk (LMT) lesion was diagnosed in a 58-year-old man. Platelet count was markedly increased and essential thrombocythemia was also diagnosed. Because of LMT disease, coronary artery bypass grafting (CABG) was performed prior to medication for essential thrombocythemia. There were no complications during the operation or in the early postoperative period. Melphalan was administered postoperatively resulting in the decrease of platelet count. Postoperative coronary angiography demonstrated that both grafts were patent; however, immediately after coronary angiography, the patient suffered from a sudden onset of myocardial infarction and cerebral infarction. The therapeutic problems associated with hematological disorder in such patients are discussed in this report.

Topics: Angina Pectoris; Cerebral Infarction; Coronary Angiography; Coronary Artery Bypass; Humans; Male; Melphalan; Middle Aged; Myocardial Infarction; Platelet Count; Postoperative Complications; Thrombocytosis; Vascular Patency

From 1982-1989, 113 hyperthermic limb perfusions were carried out in 102 patients. Ninety-three patients were treated for malignant melanoma and nine for soft tissue sarcoma. 47/93 patients had high-risk stage I melanoma with a 5-year survival rate of 89%. For the 46 patients treated for recurrent and metastatic melanoma the projected 5-year survival rate was 40%. The nine patients with soft tissue sarcoma were perfused for local recurrences or because of anatomically difficult tumor locations. 3/9 patients subsequently developed recurrent disease of the extremity; two of these patients had to be treated by amputation. The rate of major complications was low: no patient died in the postoperative course, an amputation due to toxic reaction was never required. Erythema and oedema (57%), severe skin reaction (6%) and transient nerve palsy (15%) were common side effects of therapy. Only two cases of leucopenia were observed (2%). The favourable results after hyperthermic limb perfusion show the efficacy of this method in the treatment of malignant melanoma and selected cases of soft tissue sarcoma.

Topics: Adolescent; Adult; Aged; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Female; Humans; Hyperthermia, Induced; Lung Neoplasms; Lymphatic Metastasis; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Postoperative Complications; Sarcoma; Soft Tissue Neoplasms; Survival Rate

Between 1976 and 1988, 182 patients--135 females (74.3%) and 47 males (25.7%)--were submitted to 206 isolation perfusions, using melphalan and mild hyperthermia for 34 upper and 172 lower limbs. Stage I melanoma represented 37.4% including 75.4% greater than 1.5 mm Breslow thickness or with regression, ulceration or incisional biopsy. Stage II melanoma included 62.6% of the cases. Peri-operative mortality occurred in 2/182 patients. Amputation was performed within 1 month for toxic reasons in three patients and delayed in six for progressive disease. Regional toxicity consisted in oedema (76%), pain (61%), nerve palsy (24%), thrombosis (7%), septicemia (3%), thrombocyto-granulopenia (1.5%), minor miscellaneous (52%). Mean peripheral leakage was 1.0, 7.8 and 12.4% at respectively 5, 10 and 60 minutes. Projected 5-year disease-free survival was 79% for Stage I and 27% for Stage II. Survival at 5 years was 92% in Stage I and 53.5% in Stage II. Twenty-five patients were perfused twice for recurrence or incomplete response. Although the median disease-free interval was only about 8 months, the 5-year survival was 67%. This may indicate that isolation perfusion renders melanoma metastases less aggressive despite the fact they may recur at a high rate.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arm; Axilla; Chemotherapy, Cancer, Regional Perfusion; Child; Combined Modality Therapy; Female; Humans; Hyperthermia, Induced; Leg; Lymph Node Excision; Lymphatic Metastasis; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Complications

Experience with 19 autologous bone marrow transplantations shows that this approach may produce a high proportion of complete remissions in otherwise resistant tumours. Although most responses are of short duration, they suggest that longterm disease-free survival may be achieved in patients with poor prognosis if treated earlier in the course of disease.

Topics: Adult; Bone Marrow Transplantation; Child; Cyclophosphamide; Female; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Male; Melphalan; Middle Aged; Postoperative Complications; Remission Induction

The paper deals with an analysis of the results of treatment of 344 patients with cancer of the thoracic part of the esophagus. Out of those, 104 received surgical and combined treatment and 240 (inoperable cancer) were given radiotherapy alone or in combination with local hyperthermia, general chemotherapy or intratumoral iontophoresis of chemotherapeutic agents. The procedure after Dobromyslov-Torek proved to be insufficient in most of surgical cases because there were metastatic lesions below the diaphragm. A surgical procedure which takes care of metastases is suggested. Local hyperthermia potentiated the effect of radiation treatment. The immediate results of treatment improved after intratumoral sarcolysin iontophoresis was used in conjunction with radiation therapy.

Topics: Combined Modality Therapy; Esophageal Neoplasms; Humans; Hyperthermia, Induced; Melphalan; Postoperative Complications; Radiation Injuries; Radiotherapy Dosage

Chronic granulocytic leukemia (CGL) developed in a 31-year-old man after he underwent a third renal transplant. The leukemia was initially controlled with azathioprine sodium and prednisone therapy, but eventually it entered blast cell crisis. This was controlled with an adult acute lymphocytic leukemia protocol with an excellent response. Despite discontinuing treatment with azathioprine and with the use of busulfan to control the peripheral WBC count, the patient maintained stable renal function for one year following treatment of the blast cell crisis and subsequently died of sepsis. We suggest that CGL after renal transplantation is similar to that observed in the general population and can be treated with the usual chemotherapeutic agents for the disorder without sacrificing renal function.

Topics: Adult; Allopurinol; Azathioprine; Humans; Hydroxyurea; Kidney Transplantation; Leukemia, Myeloid; Male; Melphalan; Postoperative Complications; Prednisone

From December 1978 to February 1981 91 regional hyperthermic perfusions with melphalan (1.0 or 1.5 mg/kg body weight) were performed in 87 patients with malignant melanoma of the extremities. During a one-hour perfusion with whole blood at an intramuscular temperature of 42 degrees C the flow rate was 264 +/- 62 ml/min in the upper and 495 +/- 42 ml/min in the lower limb. Apart from one intima dissection there were no serious intraoperative complications. Postoperatively one female patient died on the 19th day from acute right heart failure with severe bone marrow suppression. In six patients intransigent metastases appeared after an average of six months. One patient developed lung metastases 7 months postoperatively from which he died. Seventy-nine patients remained free of tumour during the observation period.

Topics: Adult; Aged; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Hot Temperature; Humans; Intraoperative Complications; Male; Melanoma; Melphalan; Middle Aged; Postoperative Complications; Skin Neoplasms

Topics: Adult; Amyloidosis; Antigens; Cadaver; Colchicine; Female; Humans; Immune Complex Diseases; Immunoglobulin Light Chains; Kidney; Kidney Diseases; Kidney Transplantation; Male; Melphalan; Middle Aged; Postoperative Complications; Remission, Spontaneous; Renal Dialysis; Transplantation, Homologous

Regional perfusion has been utilized in the treatment of accessible melanomas for many years. This series of 245 patients, which encompasses over ten years of experience, is presented to reevaluate the results of regional perfusions in melanomas, and perhaps to redefine the indications for such a procedure. Fifty-nine patients died from three months to over five years following the procedure, and six of the deaths were from diseases other than melanoma. The overall survival in stage I disease was 93%; stage II, 68%; and stage III, 41%. There were no survivors in stage IV. Nearly all of the recurrences and deaths from disease were seen within two years of the perfusion. These results are similar to others, and 10% to 15% better than those of conventional methods. Indications are now more definite, and include most invasive melanomas in an area accessible to perfusion technique, except in very elderly and poor risk patients, those with severe arteriosclerosis in the area concerned, and those with widespread metastases.

Topics: Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Melanoma; Melphalan; Postoperative Complications; Recurrence; Retrospective Studies

The most common causes of treatment failure in patients with malignant melanoma treated by surgical therapy alone are local or regional recurrences. These are presumed to be due to occult metastasis present at the time of the initial treatment. In an effort to control this occult regional disease, 202 patients with Stage I malignant melanoma underwent isolation-perfusion with 1-phenylalanine mustard between the years 1960 and 1970. The 2-5 and 10-year determinate survival rates were 98%, 86% and 83%, respectively. In these patients, 2% developed local recurrences, 3% developed intransit metastasis, 18% developed positive regional lymph nodes and 6% developed disseminated disease, as their first evidence of recurrence. Over 40% of these patients were benefitted by further therapy. When regional perfusion is used, the question of prophylactic lymph node dissection need not arise. There was one surgical death in this series and only a few patients had symptomatology referable to their limbs beyond 3 months.

Topics: Adolescent; Adult; Aged; Chemotherapy, Cancer, Regional Perfusion; Child; Extremities; Female; Humans; Lymphatic Metastasis; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Postoperative Complications; Skin Neoplasms; Time Factors

Topics: Amputation, Surgical; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Leg; Lymph Node Excision; Lymphatic Metastasis; Male; Melanoma; Melphalan; Neoplasm Recurrence, Local; Postoperative Complications; Prognosis

Topics: Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Follow-Up Studies; Humans; Male; Melanoma; Melphalan; Neoplasm Recurrence, Local; Neuritis; Oxygenators; Postoperative Complications; Surgical Wound Dehiscence; Surgical Wound Infection; Thrombosis; Tourniquets

Topics: Aftercare; Antineoplastic Agents; Bleomycin; Cyclophosphamide; Dactinomycin; Female; Fluorouracil; Humans; Melphalan; Methotrexate; Mitomycins; Plicamycin; Postoperative Complications; Procarbazine; Urogenital Neoplasms; Vinblastine

Topics: Adult; Aged; Arm; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Leg; Male; Mechlorethamine; Melanoma; Melphalan; Neoplasm Metastasis; Postoperative Complications; Skin Transplantation; Thiotepa

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Child; Extremities; Female; Hemorrhage; Humans; Hypotension; Leukopenia; Lymph Node Excision; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Melphalan; Methods; Middle Aged; Postoperative Complications; Sarcoma; Skin Neoplasms

Topics: Antilymphocyte Serum; Arrhythmias, Cardiac; Azathioprine; Dexamethasone; Electrocardiography; Heart Rate; Heart Transplantation; Hemodynamics; Histocompatibility; Histocompatibility Testing; Humans; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Postoperative Complications; Prednisone; Transplantation Immunology; Transplantation, Homologous

Topics: Adult; Aged; Blood Cell Count; Blood Platelets; Bone Marrow Examination; Female; Hematemesis; Hematocrit; Hemoglobinometry; Humans; Leukocytosis; Male; Megakaryocytes; Melena; Melphalan; Middle Aged; Postoperative Complications; Splenectomy; Thrombocythemia, Essential; Thrombocytosis

Topics: Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Extremities; Humans; Mechlorethamine; Melanoma; Melphalan; Neoplasm Metastasis; Neoplasms; Postoperative Complications; Surgical Procedures, Operative; Thiotepa; Toxicology; Wound Healing