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PubMed1993

Autologous bone marrow transplantation for the treatment of lung cancer.

Non-small cell lung cancer is extremely difficult to treat in all stages, and small cell lung cancer patients are cured rarely despite initial responsiveness to conventional chemoradiation therapy, even when diagnosed in limited stage. Intensive cytotoxic therapy has been explored in both small cell and non-small cell lung cancer patients, since a number of agents showed an increased response when given in high dose followed by autologous bone marrow reinfusion. The antitumor responses of single-agent high-dose trials were short-lived, but set the stage for combination chemotherapy trials given in earlier disease stages, ie, as consolidation or intensification therapy in lung cancer. In 11 published trials, 204 small cell lung cancer patients have undergone autologous bone marrow transplants. Although the transplant-related mortality rate in these studies was 7%, the long-term disease-free survival rate was 14% in a heterogeneous group of patients receiving a variety of regimens. The data gleaned from these studies suggested that a subpopulation of lung cancer patients may benefit from the use of this approach if it were to be administered at a time when the tumor burden was low. Because of the great cost of this procedure, however, third-party payers seldom provide financial coverage for these procedures. Hence, while great strides have been made in the therapy of other solid tumors, such as breast, testicular, and ovarian cancers, the role of autologous stem cell transplantation in small cell and non-small cell lung cancer remains yet to be defined.

Antineoplastic Agents↗
PubMed1993

[Platelet function after allogeneic bone marrow transplantation in Wiskott-Aldrich syndrome].

PURPOSE: To assess the platelet characteristics and functionalism in the Wiskott-Aldrich syndrome (WAS) after allogeneic BMT using cyclophosphamide and busulphan for conditioning. MATERIAL AND METHODS: Two WAS patients underwent allogeneic BMT. Platelet aggregation was studied prior to and after BMT, along with the intraplatelet amount of ADP and ATP. RESULTS: Platelet count, size and aggregation wholly recovered after BMT. The post-transplant content of platelet nucleotides was normal. CONCLUSIONS: Platelet function can be totally restored with cyclophosphamide/busulphan conditioned BMT in WAS. Platelet defects in this disease are due to defective thrombopoiesis.

Blood Platelets↗
PubMed1993

Invasive fungal sinusitis in patients undergoing bone marrow transplantation.

Invasive fungal sinusitis is becoming increasingly common in patients undergoing BMT. This study was undertaken to evaluate the incidence, presenting symptoms, diagnosis procedures, treatment and outcome of invasive fungal sinusitis. The study population comprised 423 consecutive BMT patients at Hadassah University Hospital from January 1986 to August 1992. Eleven patients (2.6%) developed invasive fungal sinusitis, 8 had underlying hematologic malignancies and 3 severe aplastic anemia (SAA). Median interval between BMT and fungal sinusitis was 22.5 days (range 2-106 days). Eight of 11 patients had protracted neutropenia (median 8 days with median neutrophil count at the time of fungal sinusitis diagnosis of 0.25 x 10(9)/l). Four patients developed GVHD before fungal sinusitis was diagnosed. Presenting symptoms were fever (100%), orbital swelling (63%), facial pain (54%) and nasal congestion (36%). In 8 patients Aspergillus species were isolated (A. flavus in 7, A. quadrilineatus in 1); in 1 patient Candida albicans was isolated and in the other 2 fungal elements were detected histologically (Fusarium and Mucor, respectively). Six of the patients underwent surgical debridement at diagnosis. Three received granulocyte transfusions. All patients received systemic amphotericin B (7 conventional and 4 amphotericin B colloidal dispersion (ABCD)). Only 2 of the 11 patients responded completely to therapy with a follow-up of 15 months. It appears that invasive fungal sinusitis is a potentially fatal complication in immunocompromised patients post-BMT. Current treatment approaches are largely ineffective and new methods of management of this serious problem are needed.

Adolescent↗
PubMed1993

Graft rejection by a population of primed CDw52- host T cells after in vivo/ex vivo T-depleted bone marrow transplantation.

We investigated a case of graft rejection after in vivo/ex vivo T-depleted BMT in a patient who had received a HVG-matched, GVH one locus-mismatched, MLC-negative graft from his cousin. In vivo/ex vivo T cell depletion was performed with Campath 1G (CP1G) and Campath 1M (CP1M), respectively. We identified a failure of CP1G to eradicate a CDw52- (Campath-negative) host T cell population as the main cause of treatment failure. The analysis also suggests that significant host-versus-donor reactivity prior to transplant, as detected by limiting dilution analysis, also contributed to graft rejection. The rejecting T cells were bifunctional in that they showed cytotoxic activity and were capable of inhibiting haemopoietic progenitor growth by producing inhibitory lymphokines.

Adult↗
PubMed1993

Acute graft-versus-host disease and the risks for idiopathic pneumonia after marrow transplantation for severe aplastic anemia.

The risks for the development of idiopathic pneumonia after allogeneic BMT were assessed in a case-series review at a single marrow transplantation center. All allogeneic marrow recipients (n = 299) (age range 1-60 years) with severe aplastic anemia (SAA) transplanted from family member donors after conditioning with CY were evaluated. Post-grafting immunosuppression consisted of MTX alone in 205 patients (69%), CY alone in 16 (5%) and a combination of the two in 78 (26%). The incidence estimate for any pneumonia within the first 200 days after transplant was 18% (95% confidence interval = 14-24%). Of 48 cases of pneumonia, CMV infection was documented in 44%, 21% were idiopathic and the remainder were either due to other infections or were not evaluated. The effect of acute GVHD on the incidence of pneumonia was examined using multivariate Cox proportional hazards models which included covariates for potential confounding factors. Consistent with previous reports, acute GVHD was associated with an increased incidence of any pneumonia (relative risk (RR) = 3.5, 95% Cl = 1.9-6.9; p < 0.001). Specifically, acute GVHD also was associated with the largest risk of idiopathic pneumonia (RR = 5.0, 95% Cl = 1.1-22; p = 0.04). In conclusion, recognition of acute GVHD as a risk factor for idiopathic pneumonia suggests that mechanisms in addition to chemoradiation damage are responsible for non-infectious lung injury after BMT.

Acute Disease↗
PubMed1993

Incidence of cataracts after single fraction total body irradiation: the role of steroids and graft versus host disease.

Eighty-eight patients who received single fraction total body irradiation (sfTBI) as part of their conditioning for allogeneic BMT have been evaluated for the risk of cataract formation. Thirty-eight (43%) have developed cataracts; 11 required surgery. With 9.5-13.6 years follow-up (median 10.7 years), all 12 recipients of unmanipulated marrow allografts have developed cataracts; the actuarial risk of needing surgery was 32 (+/- 18%, 95% confidence intervals (CI)). Ten of these 12 required high-dose steroids (prednisolone > 1 mg/kg/day) for the treatment of GVHD. Seventy-six patients received T cell-depleted allografts; 14 of 76 required post-transplant immunosuppression with high-dose steroids. With 1-9.4 years follow-up (median 5 years), the actuarial risk of cataract formation in T cell-depleted allograft recipients is 72% (+/- 52% CI), the actuarial risk for needing surgery is 20% (+/- 9% CI). Recipients of sfTBI and non-T cell-depleted allografts had a significantly greater risk of developing cataracts (p = 0.003, long rank test) and of needing surgery (p < 0.05, log rank test) than patients receiving T cell-depleted BM. Cataracts occurred more frequently in patients requiring post-transplant immunosuppression with steroids (relative risk 2.12, p < 0.01 log rank test).

Adolescent↗
PubMed1993

Hypercoagulability in patients undergoing autologous or allogeneic BMT for hematological malignancies.

Severe thrombotic alterations, such as veno-occlusive disease of the liver, may occur in the early phase following high-dose chemoradiotherapy and BMT. In this study, performed in patients with hematological malignancies subjected to allogeneic (10 cases) and autologous (20 cases) BMT, we have monitored laboratory hemostatic parameters to better understand the pathogenetic mechanism of thrombosis and particularly of veno-occlusive disease. Prothrombin time, activated partial thromboplastin time, plasma fibrinogen, markers of hypercoagulability (thrombin-antithrombin complex and prothrombin fragment F1+2); natural anticoagulants (protein C, protein S and antithrombin) together with fibrinolytic parameters (plasminogen, alpha 2-antiplasmin, tissue-plasminogen activator, plasminogen activator inhibitor and D-dimer) were assessed before transplant, on day 0 and weekly for 1 month thereafter. A hypercoagulability state, not related to an impairment of the anticoagulant and fibrinolytic systems, was documented before and after autologous and allogeneic transplant. Two patients developed veno-occlusive disease: they did not show any difference from the other patients before transplant while they presented a decrease of the natural anticoagulants along with altered fibrinolytic parameters only at the clinical onset of veno-occlusive disease. In conclusion, in this study a state of marked hypercoagulability was documented in BMT patients and the hemostatic laboratory parameters evaluated were not able to predict the occurrence of the thrombotic complications.

Antithrombin III↗
PubMed1993

Busulphan and melphalan prior to autologous bone marrow transplantation.

Twenty-four patients with a variety of malignant diseases (13 lymphoma, 4 myeloma, 1 ALL, 6 solid tumours) were treated with the alkylating agents busulphan and melphalan as a preparative regimen for autologous BMT. Thirteen males and 11 females, aged 27-53 years (median 39.5 years) received oral busulphan 1 mg/kg q6 h on days -6 to -3, followed by i.v. melphalan 140 mg/m2 on day -2 and infusion of cryopreserved haemopoietic cells on day 0. The major toxicity seen was gastrointestinal with nausea, vomiting and diarrhoea in 17 patients and severe mucositis in 22. There was no evidence of cardiotoxicity, nephrotoxicity, haemorrhagic cystitis or clinical signs of hepatic veno-occlusive disease. Twenty-three patients engrafted with the median duration of neutropenia (< 0.05 x 10(9)/l) 10 days (range 5-63 days) and thrombocytopenia (< 50 x 10(9)/l) 43 days (range 5-350 days). Three patients died of transplant-related complications. Of 15 evaluable patients with active disease at BMT, 9 responded and 6 were refractory. Sixteen evaluable patients were in CR after BMT. Seven relapsed, 1 died in remission and 8 remain in CR 12-46 months (median 29 months) later. Of the group of 13 lymphomas, overall and relapse-free actuarial survival at 36 months was 64% and 58%, respectively, while for the entire group of 24 patients these values were 39% and 34%. Busulphan and melphalan is a safe and inexpensive conditioning regimen for autologous BMT with acceptable toxicity and substantial antitumour activity particularly against lymphomas.

Actuarial Analysis↗
PubMed1993

Factors affecting hair regrowth after bone marrow transplantation.

Permanent alopecia after BMT has been reported as a side-effect associated with GVHD or after busulphan conditioning therapy, primarily in adults. We have reviewed children undergoing BMT to document the frequency of incomplete hair regrowth and to evaluate factors associated with this problem. Hair regrowth was studied in 74 children who survived > 6 months following BMT undertaken for malignant and non-malignant diseases. Alopecia was categorised as severe (< 50% of pre-transplant status), moderate (50-75%) or mild (> 75% but less than normal). Overall, 18 (24.3%) of 74 patients had mild (n = 5), moderate (n = 4) or severe (n = 9) alopecia. Risk factors for alopecia were presence of chronic GVHD (67%; p < 0.001), older age (p < 0.001) and prior cranial irradiation (42%; p = 0.03). Alopecia occurred in children receiving either busulphan (31%) or total body irradiation (16%; p = 0.15) as conditioning therapy. The highest frequency was seen in patients conditioned with busulphan with or without melphalan and who received prior cranial irradiation and/or developed chronic GVHD (75%). These data indicate that alopecia after BMT in children is a significant problem and confirm, in children, the previously noted association between alopecia and chronic GVHD and busulphan. Further risk factors of older age and prior cranial irradiation are identified. Consideration needs to be given to the use of an alternative to busulphan in children who are of older age, have received prior cranial irradiation and/or are at increased risk of GVHD.

Adolescent↗
PubMed1993

Intravenous pentoxifylline failed to prevent transplant-related toxicities in allogeneic bone marrow transplant recipients.

Based on encouraging results of a recently published study on the clinical usefulness of oral pentoxifylline (PTX) to reduce transplant-related toxicities, prophylactic pentoxifylline was administered to 31 consecutive allogeneic BMT recipients with hematological malignancies. Patients received PTX as a continuous infusion at increasing dose levels (0.50, 0.75, 1.00 and 1.25 mg/kg/h) starting 1 day prior to the conditioning regimen. At all dose levels, PTX was well tolerated with no significant side-effects. When compared with a historical control group of 61 consecutively transplanted allogeneic BMT recipients, PTX patients did not appear to experience less gastrointestinal (moderate and severe mucositis: 100% vs 68%, p < 0.001), hepatic (hyperbilirubinemia > 1.5 mg/dl: 84% vs 30%, p < 0.001) or renal (creatinine > 1.5 mg/dl: 16% vs 27%, NS) toxicity or to have a lower incidence of GVHD > or = grade III (21% vs 22%, NS). Using i.v. PTX, we were unable to reproduce the reduction in morbidity and mortality in patients undergoing BMT which has been described for prophylactic oral PTX.

Adolescent↗
PubMed1993

Constant intravenous pentoxifylline infusions in allogeneic marrow transplant recipients: results of a dose escalation study.

An uncontrolled open prospective dose escalation study of daily constant-rate 24-h i.v. pentoxifylline (PTX) infusions was performed in 24 consecutive adult patients with hematologic malignancies undergoing allogeneic BMT. The objective of this study was to determine the maximum tolerable dose and to evaluate steady-state plasma concentrations of PTX and its major active 5-hydroxylated metabolite (MI) with this application route. On each of three dose levels of PTX (10, 15 and 20 mg/kg/day), eight patients were enrolled in this study. The prominent dose-dependent and dose-limiting adverse effect attributable to PTX infusions was moderate to severe nausea and vomiting which occurred on the 15 mg/kg and 20 mg/kg dose levels. In addition, one patient on each of the higher doses developed central nervous system toxicity which manifested as acute obtundation and myoclonias. Monitoring of steady-state plasma concentrations revealed that metabolite MI contributed 70-80% to both active compounds with a dose-dependent increase of parent drug and metabolite MI concentrations. In patients pretreated by high-dose busulfan and cyclophosphamide (CY), steady-state plasma concentrations of metabolite MI were significantly increased on all dose levels over those of patients who received total body irradiation and CY as a preparative regimen. Furthermore, impairment of excretory liver function led to significant accumulation of parent drug and metabolite MI. In conclusion, constant i.v. PTX infusions in allogeneic marrow transplant recipients are limited by dose-dependent nausea and vomiting with an estimated maximum tolerable dose in the range of 10 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Growth hormone function and treatment following bone marrow transplant for neuroblastoma.

Previously, we reported that 26 children with stage III or IV neuroblastoma (NBL) treated with BMT grew poorly post-BMT and significantly worse than a comparison group of hematologic BMT patients. Furthermore, unlike the hematologic patients, there was no apparent catch-up growth. Six of these previously reported long-term (> 2 years) NBL patients surviving BMT were evaluated with growth hormone (GH) provocative testing, frequent (every 20 min) overnight GH sampling and IGF-1 determinations. Three of 6 patients were GH deficient based on subnormal responses to provocative stimuli and subnormal pooled 12 h GH values. Only one child had completely normal GH testing and his growth was normal. Four patients were tested with recombinant GH for a period of 12-21 months. Three patients demonstrated an improvement in their growth velocity on therapy. However, the overall response to GH treatment was significantly less than the growth response in children who are GH-deficient due to causes other than BMT. In summary, GH deficiency may be a frequent complication of BMT treatment of NBL. It also appears that the BMT treatment protocol employing total body irradiation and high-dose melphalan may induce GH resistance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Successful allogeneic bone marrow transplantation in an adult with aplastic anemia following orthotopic liver transplantation for non-A, non-B, non-C hepatitis.

A 29-year-old male patient presented with acute liver failure from non-A, non-B and non-C hepatitis, necessitating orthotopic liver transplantation. After operation he developed progressive pancytopenia on the basis of aplastic anemia, which was probably hepatitis associated. After therapy with GM-CSF had failed, he underwent allogeneic BMT from his HLA genotypically identical brother following a conditioning regimen of CY 50 mg/kg x 4 and 500 cGy total lymphoid irradiation. He engrafted promptly but transfusion dependency did not resolve until CMV viremia was treated with ganciclovir. The patient is alive and well 2 years after BMT.

Adult↗
PubMedDate not supplied

Patterns of mucositis and pain in patients receiving preparative chemotherapy and bone marrow transplantation.

The purpose of this study was to describe the incidence, onset, duration, severity, and other relevant characteristics of mucositis and pain in patients undergoing bone marrow transplant (BMT) who were receiving high-dose chemotherapy (cytoxan, busulfan, and etoposide) without total body irradiation. A descriptive, longitudinal design was used to study a sequential sample of 47 patients undergoing allogeneic and autologous BMT. Each day, from 9 days prior to BMT through 21 days after BMT, nine anatomic regions of patients' mouths were assessed for extent and severity of mucositis. Oral pain was measured using the Short-Form McGill Pain Questionnaire. Forty-two patients (89%) developed mucositis, which, on average, began 3 days after transplant, lasted 9.5 days, and resolved by 12.6 days post-transplant. Thirty-six patients (86%) reported pain that began, on average, 4.5 days after transplant, lasted 6.5 days, and resolved by 11 days post-transplant. During the initial weeks following BMT, systematic assessment of the oral cavity areas that are at high risk for mucositis should assist nurses in detecting early oral complications and in initiating specific interventions. Additionally, attention needs to be given to the assessment and management of mucositis-related oral pain. Future nursing research should be conducted to examine efficient clinical methods of assessing mucositis and oral pain and to test prophylactic and therapeutic interventions.

Adolescent↗
PubMed1993

[Autologous bone marrow transplantation in children with malignant diseases. Bone marrow harvest and procedure-related toxicity].

The aim of this paper was to present the results of bone marrow harvest followed by cryopreservation in 22 children with various malignant diseases, and the clinical course of autologous bone marrow transplantation (ABMT) performed in 10 children (three with acute lymphoblastic leukemia (ALL), three with acute myeloblastic leukemia (AML) and four neuroblastoma stage IV (NB)). In 20/22 children the harvested bone marrow contained a sufficient number of granulocyte-macrophage-colonyforming units (GM-CFU) for later marrow reinfusion. Hematological reconstitution was obtained in all 10 children who underwent ABMT. No child died of toxicity. The median time to neutrophil count > 0.5 x 10(9)/l, thrombocyte count > 50 x 10(9)/l and to discharge from hospital were 34, 49 and 29 days respectively. Five children are alive with no evidence of active disease 11-21 months after ABMT. Five children have suffered relapse and have died. It was concluded that sufficient amounts of precursor bone marrow cells may be harvested in children during a pause in cystostatic therapy. The acute toxicity of ABMT in children with malignant diseases was only moderate.

Adolescent↗
PubMed1993

ABMT for early isolated extramedullary relapse of childhood ALL.

From July 1987 to July 1991, 12 children underwent AMBT following high-dose cytarabine (HD Ara-C) plus 14.4 Gy hyperfractionated total body irradiation (hyfr-TBI) for early isolated extramedullary relapse of ALL, while in first BM remission. No patient received intrathecal prophylaxis following AMBT. One patient died on day +5 due to sepsis and three patients, two of them transplanted in second and third CNS relapse, respectively, died from BM relapse occurring 1.5, 4 and 5 months after AMBT. Eight of the 12 survive disease-free with a median follow-up of 24 months (range 14-62 months). The toxicity of HD Ara-C plus hyfr-TBI was acceptable and well controlled with supportive therapy. These results suggest that ABMT following HD Ara-C plus hyfr-TBI may eradicate leukemia from extramedullary sites of ALL relapse.

Adolescent↗