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Autologous bone marrow transplantation (ABMT) is an increasingly effective treatment option for both hematologic malignancies and solid tumors. The dose-limiting toxicity of bone marrow suppression after intensive chemotherapy and/or radiation therapy can be minimized by reinfusing the patient's stored marrow. However, the ABMT procedure involves a period of profound neutropenia before the reinfused marrow engrafts and it also carries a significant risk of major organ toxicities. Common adverse effects of the procedure include mucositis, pneumonitis, renal failure, and veno-occlusive disease of the liver. In this article, Orem's Self-Care Model is used as a framework for assessing ABMT patients with the goal of recognizing developing complications early.
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PMID:Assessment of the autologous bone marrow transplant patient according to Orem's self care model. 147 87

Bone marrow transplantation from an HLA-identical sibling is increasingly used as a curative therapy for patients with hemopoietic stem cell disorders including acute leukemia, chronic myelogenous leukemia and severe aplastic anemia. Between March 1983 and March 1991, we performed 86 cases of allogeneic bone marrow transplantation (BMT) for the patients with hemopoietic stem cell disorders: 25 acute myelogenous leukemia (AML); 15 acute lymphoblastic leukemia (ALL); 20 chronic myelogenous leukemia (CML); and 26 severe aplastic anemia (SAA). Ten out of 25 AML are in disease free survival (DFS). The causes of death were recurrence of leukemia (12), acute GVHD (3), sepsis (1) and veno-occlusive disease (1). Nine of 15 ALL are in unmaintained remission. Thirteen out of 20 CML are in DFS. Among 26 SAA, 21 are enjoying DFS, but 1 died of engraftment failure, 3 of graft rejection followed by cytomegalovirus (1) and aspergillus pneumonia (1). Comparing the survival between standard [less than or equal to CR1: 9/14 (64%)] and high risk [greater than or equal to CR1: 1/11 (9%)] AML, our data suggest that preparative regimen for high risk AML was not potent enough to eradicate the minimal residual disease in advanced AML. Although our cases are limited and the follow-up period is short, our result of ALL [overall: CCR (60%), standard risk (adult less than or equal to CR1, children less than or equal to CR2; 8/11 (73%) and high risk; 1/4 (25%)] and CML [overall: 65%, CP; 9/10 (90%), AP; 4/6 (67%), BP; 0/4 (0%)] are optimistic. It is of our interest that the incidence of death related with IP (1/33: 3%) and with AGVHD 94/33: 12%) were much less than that of other's observation but the explanation for this still remains to be clear.
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PMID:Allogeneic bone marrow transplantation for the patients with hemopoietic stem cell disorders: CUMC experience. 151 32

Twenty-one patients (median age = 34, range = 10-49; F:M = 7:14) received a preparative regimen consisting of busulfan 4 mg/kg/day x 4, cytosine arabinoside 2 g/m2/12 h x 4 and cyclophosphamide 60 mg/kg/day x 2 ('BAC' regimen) for allogeneic bone marrow transplantation. Out of 12 patients with acute myeloid leukemia (AML), two were in first remission, six were in second remission and four had resistant, relapsed disease or prolonged marrow aplasia after induction chemotherapy. Five of the 12 patients with AML had secondary AML. Four patients had transfusion-dependent myelodysplastic syndrome. Three patients with chronic myeloid leukemia were in the accelerated phase and two were in the blastic phase. Organ toxicities related to the preparative regimen were graded. Liver toxicity occurred in 11 patients, two of these were fatal veno-occlusive disease (VOD) (10%). Nineteen of the 21 patients had grade 2 or less diarrhea, and 13 also had mucositis. One patient developed grade 3 cardiac toxicity, and one other patient had grade 1 skin toxicity. Four patients had gross hematuria related to treatment (19%). No renal, pulmonary or CNS toxicities were encountered. Ten patients have died, two from regimen-related hepatic VOD. Of the remaining eight deaths, four were from respiratory failure in four patients (one case each of Pneumocystis pneumonia, CMV pneumonia, bronchiolitis obliterans associated with chronic graft-versus-host disease, and interstitial pneumonitis complicated pulmonary emboli), and one patient each from GI bleeding, cardiac arrhythmia, sepsis and CNS bleeding. Thus far, only one patient transplanted for secondary AML in second remission relapsed at day 230.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allogeneic bone marrow transplantation in high-risk myeloid disorders using busulfan, cytosine arabinoside and cyclophosphamide (BAC). 154 49

Thirty-six patients with advanced hematologic malignancy were entered into a Phase I study designed to define the maximum tolerated dose of unshielded total body irradiation delivered from dual 60 Cobalt sources at an exposure rate of 8 cGy/min and given in fractions twice daily for total doses ranging from 12 Gy to 17 Gy. All patients received cyclophosphamide, 120 mg/kg administered over 2 days before total body irradiation. Allogeneic marrow was infused from HLA-identical siblings (n = 29) or one locus HLA incompatible family members (n = 3); three patients received cryopreserved autologous marrow and one patient received syngeneic marrow. The maximum tolerated dose of total body irradiation given as 2 Gy fractions twice a day was 16 Gy. One of eight patients receiving 12 Gy, none of four receiving 14 Gy, three of 20 receiving 16 Gy, and two of four receiving 17 Gy developed severe (Grade 3-4) regimen-related toxicity. The primary dose limiting toxicity was pneumonitis, followed by veno-occlusive disease of the liver, renal impairment, and mucositis. Five patients (14%) are alive, four disease-free 798-1522 days posttransplant. Twenty (56%) relapsed posttransplant. Further investigation of regimens containing 16 Gy of hyperfractionated total body irradiation is warranted to assess anti-tumor efficacy.
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PMID:Marrow transplantation following escalating doses of fractionated total body irradiation and cyclophosphamide--a phase I trial. 163 36

One hundred and six patients with standard risk leukaemia were given fractionated TBI prior to allogeneic (72 cases, 27 of whom were T-depleted) or autologous (34 cases) bone marrow transplantation (BMT). Disease free survival at 5 years is 68% for allogeneic non T-depleted BMT and 33% for T-depleted BMT. Deaths are related to relapse, GVHD, infections, pneumonitis, encephalitis, VOD, AIDS, rejection.
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PMID:Results of fractionated TBI prior to bone marrow transplantation in standard risk leukaemia at Marseille. 224 38

Twenty-six patients with recurrent leukemia following allogeneic marrow transplantation received a second marrow transplant between 1.5 and 78 months (median 26) after the initial transplant. Preparative regimens for second transplant included multi-agent chemotherapy with total body irradiation, 2.0-10.0 Gy (five patients), dimethylbusulfan alone (one patient), and dimethylbusulfan or busulfan plus cyclophosphamide (20 patients). One patient died before engraftment of infection and 18 died after engraftment from veno-occlusive disease (4), infection (2), idiopathic pneumonia (3), cytomegalovirus pneumonia (3), leukemia (5) and encephalopathy (1). Seven patients (27%) survive 12-38 months (median 26); five (19%) are disease-free and two have recurrent leukemia. Two of the five disease-free survivors have chronic graft-versus-host disease. All of the surviving patients received dimethylbusulfan or busulfan plus cyclophosphamide and six of the seven surviving patients were among 11 patients transplanted more than 2 years after the first transplant whereas only one was among the 15 transplanted in less than 2 years. Those who have second marrow transplants one or more years after their initial transplant are more likely to benefit, while those who are less than 1 year from initial transplant appear to benefit the least.
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PMID:Second marrow transplants in patients with leukemia who relapse after allogeneic marrow transplantation. 304 66

Dogs with malignant lymphoma were given chemotherapy consisting of nitrogen mustard, vincristine sulfate, prednisone, L-asparaginase, and 6-mercaptopurine (MOPA-6) for 14 days. Among 62 dogs that completed treatment with MOPA-6, 47 (76%) had complete remission, and 13 (21%) had partial remission and 2 had no response to chemotherapy. Twenty-two of the 62 dogs were not returned by their owners for additional therapy and died 15 to 391 (median 21) days after MOPA-6 from infections or recurrent disease. A median of 1 month after starting MOPA-6 therapy, 40 dogs (35 in complete remission, 5 in partial remission) were given total body irradiation (TBI), followed by infusion of fresh autologous marrow. Twenty dogs were given 13.5 Gray (Gy) of TBI at 4 centi-Gray (cGy)/min. Among 16 evaluable dogs, 7 had recurrence of lymphoma at a median of 169 days. Two dogs died with veno-occlusive disease of the liver, 3 with pneumonia, 3 with hemorrhage, and 1 was killed. Twenty dogs were given 11.8 to 14.7 Gy of TBI at 2 cGy/min. Among 14 evaluable dogs, 9 had recurrence of lymphoma at a median of 117 days. The remaining 5 dogs were killed at 110 to 680 days; lymphoma was not present at necropsy. The results indicated that doses of TBI of 11.8 to 14.7 Gy did not reduce the recurrence of lymphoma, compared with results obtained in a previous study with 8.4 Gy of TBI. Furthermore, increased doses of TBI increased acute and delayed toxicities. Alternatively, recurrent disease may have been due to lymphoma cells contained in the infused remission marrow.
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PMID:Autologous marrow transplantation as consolidation therapy for canine lymphoma: efficacy and toxicity of various regimens of total body irradiation. 390 41

We retrospectively reviewed the regimen-related toxicity associated with busulphan (1 mg/kg orally QID days -7 to -4) and cyclophosphamide (60 mg/kg IV days -3 and -2) (Bu/Cy) chemotherapy in 69 consecutive patients who underwent autologous bone marrow transplantation (ABMT). Twenty-four patients received bone marrow (BM) alone, 22 received BM plus post-transplant granulocyte-colony stimulating factor (G-CSF) and 23 received peripheral blood progenitor cells (PBPC) +/- BM plus post-transplant G-CSF. Toxicity was scored using the criteria of Bearman. Grade II and III toxicities included mucosa (38%), liver (8%), central nervous system (5%), kidney (5%), heart (3%), pericardium (2%), bladder (2%) and lung (2%). There were five treatment related deaths (7%) from pneumonitis (2) and veno-occlusive disease, pulmonary hemorrhage and sepsis (1 each). Post-transplant G-CSF (+/- PBPC) resulted in a trend (p = 0.07) towards a reduction in post-transplant stomatitis, but did not impact on the already low incidence of other organ toxicities. As Bu/Cy for ABMT is associated with minimal non-hemopoietic toxicity, the addition of other cytotoxic agents is justified in an attempt to augment the anti-tumour effect of this conditioning regimen.
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PMID:High dose busulphan/cyclophosphamide for autologous bone marrow transplantation is associated with minimal non-hemopoietic toxicity. 752 88

Bacterial pneumonia as an important complication of bone marrow transplantation (BMT) has not been subjected to comprehensive analysis. Two hundred fifty-five consecutive allogeneic and autologous BMT recipients, ranging in age from 1 month to 53 years, were prospectively followed for 3 days to 3 years (median, 108 days) for development of bacterial pneumonia. Etiology, place acquired, chest radiography, and outcome were recorded and the association between bacterial pneumonia and demographic and clinical variables was analyzed. Thirty-seven (15%) patients experienced 52 episodes of bacterial pneumonia: onset of 13 episodes occurred within 30 days after transplantation, 10 episodes occurred on days +31 to +100, and 29 episodes occurred thereafter. Bacterial pneumonia was the terminal event or contributed to fatal outcome in 8 patients (22% of bacterial pneumonia cases, 3% total study population). Mortality due to hospital-acquired pneumonia (6/21) was significantly higher than (P = 0.03). Bacterial pathogens were identified in 27 (52%) episodes. During the first 100 days after BMT, hospital-acquired Gram-negative bacteria predominated, caused mainly by Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter lwoffi, and Enterobacter cloacae. After day +100, community-acquired, Gram-positive bacteria predominated, particularly Streptococcus pneumoniae. Haemophilus influenzae occurred periodically. Considering all episodes, significant association was found between bacterial pneumonia and veno-occlusive disease (VOD) (P < 0.01) and chronic graft-versus-host disease (GVHD) (P < 0.02). For culture-positive episodes, the association between bacterial pneumonia and VOD was significant (P < 0.001) and borderline for acute GVHD (P = 0.07). It is concluded that VOD and GVHD are positively associated with post-BMT bacterial pneumonia. Its incidence, etiology, risk factors, and outcome are important considerations in its prevention and treatment.
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PMID:Bacterial pneumonia in recipients of bone marrow transplantation. A five-year prospective study. 757 Sep 75

Respiratory failure is the main cause of death in patients undergoing bone marrow transplantation (BMT). In this paper, clinical and research aspects as well as diagnostic, prophylactic and therapeutic strategies concerning the various forms of pulmonary and bronchial complications, which may evolve after BMT, are discussed. Both cytomegalovirus (CMV)-induced interstitial pneumonia (PM) and the idiopathic pneumonia syndrome rarely occur in the cytopenic phase post-BMT. Haematological reconstitution with donor type cells seems to be a prerequisite to the development of these complications, suggesting a key role of immunological reactions. While CMV pneumonia can be effectively treated or prevented by ganciclovir, the idiopathic syndrome is usually fatal. Due to improved prophylaxis and therapy, lethal interstitial PM due to Pneumocystis carinii, herpes simplex, varizella zoster or Toxoplasma gondii as well as lethal PM caused by bacteria or Candida species are comparatively rare events. Aspergillus species, on the other hand, have emerged as frequent causative pathogens in lethal PM during the past years. Prolonged granulocytopenia and prolonged medication with corticosteroids are major risk factors of pulmonary aspergillosis, which is usually fatal; effective prophylaxis may be achieved by sterile air supply during the hospital stay and by inhalation of amphotericin B thereafter. Pulmonary haemorrhage, as diagnosed by bronchoalveolar lavage (BAL), may develop due to the toxicity of the conditioning regimen, or may be secondary to infectious PM of various kind. Congestive heart failure or the application of cytokines might give rise to the development of pulmonary oedema. Patients with hepatic veno-occlusive disease have a high risk of subsequent pulmonary complications, possibly on the basis of toxic lung injury. Venous thromboembolism or air embolism may occur; they are usually venous catheter-associated. Pleural effusions may develop secondary to infection, congestive heart failure, veno-occlusive disease, pulmonary embolism or malignancy. Patients with bronchiolitis obliterans, which leads to progressive respiratory failure, present with an obstructive pattern in lung function tests and hyperinflated lungs on chest radiographs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The lung as a critical organ in marrow transplantation. 772 20


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