Pilot study of allogeneic G-CSF-stimulated bone marrow transplantation: harvest, engraftment, and graft-versus-host disease.

Peripheral blood progenitor cell (PBPC) harvests mobilized by granulocyte colony-stimulating factor (G-CSF) contain more CD34+ cells and provide more rapid engraftment than do bone marrow (BM) harvests. However, some reports have suggested a higher risk of chronic graft-versus-host disease (GVHD), possibly because such PBPC harvests contain approximately 10 times more T lymphocytes than do BM harvests. Some groups are attempting to combine the faster engraftment of PBPCs with the lower incidence of GVHD observed after BM transplantation by using G-CSF-primed BM conventionally harvested from iliac crests for allogenic BM transplantation. We report the results of a pilot study of 38 allogeneic transplants using G-CSF-stimulated BM from related donors, with a focus on the harvest composition, engraftment, and incidence of acute and chronic GVHDs.

Criopreservaçäo de medula óssea e células pluripotentes periféricas utilizando um congelador programável: experiência em 86 congelamentos / Cryopreservation of bone marrow and peripheral blood stem cells using a controlled rate freezing system: experience on 86 procedures

A infusao de células hematopoéticas totipotentes criopreservadas permite a recuperaçao da hematopoese após quimioterapia mieolblativa. Objetivo. A formaçao de cristais de gelo durante o processo de congelamento é o fator principal que causa ruptura das estruturas celulares. A criopreservaçao dessas células a uma taxa constante preveniria os danos causados pelo congelamento brusco. Métodos. Vinte e três pacientes com mediana de 25 anos (variaçao 3-57) tiveram a medula óssea e/ou células-tronco periféricas (CTP) coletadas no período de março de 1993 a outubro de 1994, totalizando 86 congelamentos. Os pacientes apresentavam as seguintes neoplasias: linfoma nao-Hodgkin (n=5), leucemia mielóide aguda (n=8), leucemia linfóide aguda (n=6), doença de Hodkin (n=3) e mieloma múltiplo (n=1). O congelamento foicontrolado por um computador, acoplado ao sistema, às seguintes temperaturas: -1 graus Celsius/min até -45 graus Celsius e depois a -10 graus Celsius/min até -80 graus Celsius. Após o congelamento, as células foram mantidas em freezer a -110 graus Celsius até o momento da infusao. Para obtençao das CTP, empregou-se o fator de crescimento estimulante de granulócitos (G-CSF). Resultados. Uma mediana de 3,16 x 10(8) céls./kg (variaçao 0,86-24,22) de CTP e 2,03 x 10(8) céls./kg (variaçao 0,19-12,21) de medula óssea foi congelada. A mediana para atingir granulócitos maior ou igual a 500/muL e plaquetas maior que 20.000/muL foi de 12 dias (variaçao 8-40) e 31 dias (variaçao 8-80), respectivamente. Todos os pacientes tiveram recuperaçao hematopoética após a infusao das células criopreservadas. Conclusao. A criopreservaçao em congelador program vel permite o armazenamento de células hematopoéticas e, potencialmente, pode causar menor dano celular.

[Cryopreservation of bone marrow and peripheral blood stem cells using a controlled rate freezing system: experience with 86 procedures]. / Criopreservação de medula óssea e células pluripotentes periféricas utilizando um congelador programável: experiência em 86 congelamentos.

UNLABELLED: The cryopreservation of hematopoietic stem cells can be used for rescuing the hematopoiesis after high dose chemotherapy. PURPOSE: The ice crystal formation during the freezing procedure is the key point that can be harmful to the cells. The cryopreservation of hematopoietic stem cells in a controlled-rate freezer could decrease the cell damage. METHODS: Twenty-three patients with a median age of 26 years (range 03-57) had bone marrow and/or peripheral blood stem cells harvested from March 1993 through October 1994, ending up to 86 freezing procedures. The patient's diagnoses are as follows: Non-Hodgkin's Lymphoma (n = 5); Acute Myelogenous Leukemia (n = 8); Acute Lymphocytic Leukemia (n = 6); Hodgkin's disease (n = 3); Multiple Myeloma (n = 1). The cells were frozen away in a controlled-rate freezer chamber at the following rate: -1 degree C/min from room temperature to -45 degrees C and then, at -10 degrees C/min down to -80 degrees C. After freezing, the cells were kept into mechanical freezers until the marrow infusion. To mobilize PBSC (peripheral blood stem cells), G-CSF (granulocyte colony stimulating factor) was given. RESULTS: A median of 3.16 x 10(8) cells/kg (range 0.86-24.22) of PBSC and 2.03 x 10(8) cells/kg (0.19-12.21) of bone marrow cells were frozen. The median time to reach granulocytes greater than 500/microL and platelets greater than 20,000/microL was 12 days (range 8-40) and 31 days (range 8-80), respectively. All patients had marrow engraftment after infusion of hematopoietic stem cells. CONCLUSION: The cryopreservation procedure using a controlled-rate freezer can store hematopoietic stem cells and potentially, cause less damage to the cells.

Herpes Simplex Virus Shedding in Bone Marrow Transplant Recipients During Low-Dose Oral Acyclovir Prohylaxis.

A 400mg dose twice-a-day oral acyclovir prophylaxis regimen was evaluated in 50 allogeneic transplant recipients. Twenty (40%) patients experienced 24 episodes of herpes simplex virus (HSV) shedding; l7 (70.8%) occurring during prophylaxis. Thirteen of such episodes were asymptomatic and, in three, it was difficult to differentiate severe mucositis from viral lesions. In the remaining one, HSV pneumonia was suspected after a bronchoalveolar lavage (BAL) procedure performed in an attempt to early detection of cytomegalovirus (CMV). All cases responded to acyclovir therapy or dose adjustment suggesting that acyclovir resistance did not account for the occurrence of infection in our patients. These data demonstrated that oral acyclovir prophylaxis, 400mg dose twice-a-day, was inadequate to suppress viral shedding. The bronchoalveolar lavage procedure in a patient with HSV shedding could precipitate HSV spread to the lungs and the occurrence of pneumonia.

Clinical features and successful recovery from disseminated nocardiosis after BMT.

Nocardiosis has rarely been described after BMT. When the doses of immunosuppressive therapy were tapered, a 46-year-old BMT recipient developed chronic graft-versus-host disease (GVHD) and immunosuppresive drugs were increased. Sixteen days later the patient developed nocardiosis diagnosed by lung biopsy. Trimethoprim/sulfamethoxazole (TMP/SMZ) was initiated but the doses were reduced because of rising creatinine levels. Skin and cerebral dissemination of nocardiosis was observed and TMP/SMZ doses were increased. After 4 months, the brain lesion was unaltered despite resolution of pulmonary lesions. Clinical improvement was observed after drainage of the brain abscess.

Small noncleaved cell lymphoma and leukemia in adults. A retrospective study of 65 adults treated with the LMB pediatric protocols.

In France, more than 80% of children with Burkitt's lymphoma or Burkitt's leukemia (ALL3) are now cured with the LMB (B-cell non-Hodgkin's lymphoma and B-ALL) protocols of the Société Française d'Oncologie Pédiatrique, but so far, poor results have been obtained in the few adult studies available. We have analyzed the experience with LMB protocols in adult patients. This retrospective study involved 65 adult patients with small noncleaved cell lymphoma or ALL3 treated with the LMB protocols. They were 17 to 65 years old and not previously treated. Human immunodeficiency virus-infected patients were excluded. The diagnoses were made between September 1984 and August 1991. According to the Murphy classification, 12 patients (18%) had stage I or II disease, 25 (38%), stage III disease; 4 (6%), stage IV disease; and 24 (37%), ALL3 (> or = 25% blasts). According to the Ann Arbor classification, 9 patients had stage I disease; 8 patients, stage II; 5 patients, stage III; 21 patients, stage IV disease; and 22 patients, ALL (> or = 30% blasts). Twelve patients had central nervous system (CNS) involvement before treatment. Thirty-nine patients were treated according to the LMB 84 protocol scheme; 14 according to the LMB 86 protocol, and 12 patients received the LMB 84 induction courses followed by the LMB 86 consolidation courses. Three patients underwent bone marrow transplantation (BMT) while in second complete remission (CR) and 3 others had refractory disease. There were some protocol violations caused by empirical medical decisions: local irradiation was performed in 4 patients, 2 patients received prophylactic radiation to the brain that was not specified in the protocol, 13 patients underwent BMT in first CR, and methotrexate doses were modified in 10 patients. Fifty-eight patients (89%) achieved a CR. There were four (6%) primary induction treatment failures, and three (4%) early treatment-related deaths. Eight patients relapsed between 2 and 30 months after CR (median, 4.7 months). Forty-seven patients are alive in CR (45 first CR, 2 second CR) with a median follow-up of 57 months (24 to 93 months). There were five toxicity-related deaths among patients in CR including four BMT-related deaths and five deaths caused by refractory relapses. One patient died in CR at 62 months of rectal cancer. The 3-year overall survival rate is 74% (SE = 5). According to the stages in the Murphy classification, the 3-year survival rates are stages I and II, 100%; stage III, 80% (SE = 7); and stage IV and ALL, 57% (SE = 8). Seven of 12 patients with initial CNS disease are alive with a median survival of 56 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Localized stage non-Hodgkin's lymphoma of the testis: a retrospective study of 16 cases.

The present report concerns a retrospective study of 16 patients with localized intermediate- or high-grade non-Hodgkin's lymphoma of the testis treated in one institution from 1973 to 1990. Ann Arbor stage of disease was IE in 11 and IIE in 5 cases. All except one patient underwent initial inguinal orchidectomy, 11 were disease free after surgery and 12 received inverted Y radiation therapy. All patients achieved a complete remission (CR). Relapse occurred in 8 of 9 patients who did not receive initial chemotherapy, but in only 3 of 7 patients initially treated with chemotherapy including anthracyclins. In 3 cases relapse was confined to the CNS, while diffuse relapse in 8 others included 4 cases of CNS involvement. Eight patients are now alive in CR (5 in first CR, 1 in second CR and 2 in third CR) with a median follow-up of 68.5 months (range 54-101). Chemotherapy thus emerges as the initial treatment of preference for localized testicular lymphoma. Therapy should be preceded by a thorough assessment of the stage of disease and due to the high frequency of CNS relapse, CNS prophylaxis should be considered for all patients.

Super-high-risk germ-cell tumors: a clinical entity. Report of eleven cases.

Among patients suffering from nonseminomatous germ-cell tumor, with a poor prognosis, a subset underwent respiratory failure and died very early in the course of their treatment. Between 1982 and 1989, 11 out of 56 such patients (20%) died within the first 5 weeks of chemotherapy. The clinical, radiological, biological and infectious characteristics of these patients were analyzed. Nine patients had extensive pulmonary metastases and the 2 others presented a bulky mediastinal mass with pleural effusion. All patients experienced acute respiratory distress during chemotherapy and underwent mechanical ventilation. All patients were febrile, and septicemia was documented in 7 cases. WHO grade 4 and grade 1-2 renal toxicities occurred in 3 and 4 patients respectively. There was no tumor lysis syndrome. All patients died within 35 days from the start of therapy; 4 were autopsied. These 11 patients represent a clinical entity, having what we called super-high-risk germ cell tumors. Early death is related to pulmonary distress within the first 5 weeks of therapy. The origin of the pulmonary distress is multifactorial: bulky disease of the chest, infection, and interstitial fibrosis. Immediate full-dose standard chemotherapy in association with intensive supportive care is recommended in the management of these patients.