ABSTRACT
Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.
Subject(s)
Cord Blood Stem Cell Transplantation , Gastrointestinal Tract/immunology , Graft vs Host Disease/therapy , HLA Antigens/immunology , Hematologic Neoplasms/therapy , Myeloablative Agonists/therapeutic use , Transplantation Conditioning , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Budesonide/therapeutic use , Calcineurin/metabolism , Calcineurin Inhibitors , Child , Child, Preschool , Enzyme Inhibitors/therapeutic use , Female , Gastrointestinal Tract/pathology , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Hematologic Neoplasms/pathology , Histocompatibility Testing , Humans , Infant , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Severity of Illness Index , Survival Analysis , Transplantation, Homologous , Treatment OutcomeABSTRACT
MHC Class II deficiency is a rare primary immunodeficiency disease characterized by absent HLA Class II expression resulting in CD4 lymphopenia, lack of Ag-specific responses and recurrent infection. Without successful allogeneic SCT, most children succumb to infection within the first decade of life. To date, alternative donor transplants for this disorder have been inferior to SCT for other forms of combined immunodeficiency disease due to an increased incidence of graft rejection, GVHD and death from infections generally acquired before haematopoietic cell transplantation. This study details the transplant outcome of 16 affected children consecutively transplanted at four centers since 1990, 8 of whom required mechanical ventilation pretransplant. Stem cells were derived from an HLA-mismatched family member (n=10), an HLA-matched unrelated adult donor (n=4), or an unrelated cord blood donor (n=2). Graft failure occurred in five children, all of whom underwent a second SCT. Six patients developed acute GVHD although no patient developed chronic GVHD after primary transplantation. CD4 T-cell reconstitution remained below the normal range for age, suggesting defective thymopoiesis after allo-SCT. Nonetheless, 69% of children survive without GVHD at a median follow-up of 5.7 years, indicating improved outcomes compared with previous studies.
Subject(s)
HLA Antigens/immunology , Hematopoietic Stem Cell Transplantation/methods , Histocompatibility Antigens Class II/immunology , Immunologic Deficiency Syndromes/surgery , Child, Preschool , Female , Histocompatibility Antigens Class II/genetics , Histocompatibility Testing , Humans , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/immunology , Infant , Infant, Newborn , Male , Tissue DonorsABSTRACT
Over 40 000 hematopoietic cell transplantations (HCT) are performed worldwide each year, increasing the number of transplant survivors returning to school, the work place and overseas travel. Outbreaks of measles and mumps in immunocompetent individuals and the increased morbidity associated with primary varicella and shingles in older individuals highlight the need for effective vaccination of these vulnerable patients. In current post-HCT vaccination guidelines, only the measles, mumps and rubella vaccine (MMR) and the live-attenuated varicella vaccine (LAVV) designed to prevent primary varicella in varicella zoster seronegative individuals are permissible post HCT and only in select patient groups. All other vaccines, including the shingles vaccines, are contraindicated post HCT. Current data, primarily in pediatric HCT recipients, demonstrate a 60-70% response following a single MMR or LAVV. A two-dose schedule increases the seroconversion rate following these vaccines. This review will highlight published studies on the immunogenicity of MMR and the LAVV, areas in which data on these vaccines are lacking, the criteria for their use in patients transplanted at our center and potential studies to answer questions posed by the growing number of transplant survivors and their physicians on how to safely administer live-attenuated viral vaccines.
Subject(s)
Chickenpox Vaccine/therapeutic use , Disease Outbreaks , Hematopoietic Stem Cell Transplantation , Herpes Zoster/prevention & control , Measles-Mumps-Rubella Vaccine/therapeutic use , Measles/prevention & control , Mumps/prevention & control , Chickenpox Vaccine/immunology , Herpes Zoster/epidemiology , Herpes Zoster/immunology , Humans , Measles/epidemiology , Measles/immunology , Measles-Mumps-Rubella Vaccine/immunology , Mumps/epidemiology , Mumps/immunology , Practice Guidelines as Topic , Vaccines, Attenuated/immunology , Vaccines, Attenuated/therapeutic useABSTRACT
Opportunistic pulmonary infections are a major cause of post-transplant morbidity and mortality. Among these infections, Aspergillus is a common cause of fatal pneumonia. Owing to the precarious clinical condition of many patients who acquire invasive mold infections, clinicians often treat them on the basis of radiographic findings, such as the halo sign. However, in patients who do not respond to treatment or who have uncommon presentations, bronchoscopy or lung biopsy looking for other pathogens should be considered. This study describes two cases in which the radiographic halo signs characteristic of Aspergillus were in fact due to Legionella jordanis, a pathogen that has been culture proven only in two patients previously (both of whom had underlying lung pathology) and diagnosed by serologic evidence in several other patients. In immunocompromised patients, Legionella can present as a cavitary lesion. Thus, presumptive treatment for this organism should be considered in post-transplant patients who do not have a classic presentation for invasive fungal infection and/or who fail to respond to conventional treatment. These cases illustrate the importance of obtaining tissue cultures to differentiate among the wide variety of pathogens present in this patient population.
Subject(s)
Aspergillosis/diagnostic imaging , Hematopoietic Stem Cell Transplantation/adverse effects , Legionellosis/diagnostic imaging , Lung Diseases, Fungal/diagnostic imaging , Opportunistic Infections/diagnostic imaging , Adolescent , Adult , Aspergillosis/diagnosis , Aspergillosis/immunology , Aspergillosis/pathology , Aspergillus/isolation & purification , Biopsy , Diagnosis, Differential , Humans , Legionella/isolation & purification , Legionellosis/diagnosis , Legionellosis/immunology , Legionellosis/pathology , Lung Diseases, Fungal/immunology , Lung Diseases, Fungal/pathology , Male , Opportunistic Infections/diagnosis , Opportunistic Infections/immunology , Opportunistic Infections/pathology , RadiographyABSTRACT
T-cell depleted allogeneic hematopoietic SCT (TCD-HSCT) have shown durable disease-free survival with a low risk of GVHD in patients with AML. We investigated this approach in 61 patients with primary refractory or relapsed non-Hodgkin lymphoma (NHL), who underwent TCD-HSCT from January 1992 through September 2004. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, followed by either thiotepa and cyclophosphamide (45 patients) or thiotepa and fludarabine (16 patients). We determined the second-line age-adjusted International Prognostic Index score (sAAIPI) before transplant transplant. Median follow-up of surviving patients is 6 years. The 10-year OS and EFS were 50% and 43%, respectively. The relapse rate at 10 years was 21% in patients with chemosensitive disease and 52% in those with resistant disease at time of HSCT. Nine of the 18 patients who relapsed entered a subsequent CR. OS (P=0.01) correlated with the sAAIPI. The incidence of grades II-IV acute GVHD was 18%. We conclude that allogeneic TCD-HSCT can induce high rates of OS and EFS in advanced NHL with a low incidence of GVHD. Furthermore, the sAAIPI can predict outcomes and may be used to select the most appropriate patients for this type of transplant.
Subject(s)
Hematopoietic Stem Cell Transplantation/mortality , Lymphocyte Depletion/mortality , Lymphoma, Non-Hodgkin , Adolescent , Adult , Child , Child, Preschool , Disease-Free Survival , Follow-Up Studies , Graft vs Host Disease/mortality , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Incidence , Lymphocyte Depletion/adverse effects , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/therapy , Middle Aged , Predictive Value of Tests , Prognosis , Risk Factors , Transplantation Chimera , Transplantation, Homologous , Young AdultABSTRACT
Daclizumab has been shown to have activity in acute GVHD, but appears to be associated with an increased risk of infection. To investigate further the long-term effects of daclizumab, we performed a retrospective review of 57 patients who underwent an allogeneic hematopoietic stem cell transplant from January 1993 through June 2000 and were treated with daclizumab for steroid-refractory acute GVHD. The median number of daclizumab doses given was 5 (range 1-22). GVHD was assessed at baseline, days 15, 29 and 43. By day 43, 54% patients had an improvement in their overall GVHD score, including 76% patients aged < or =18. Opportunistic infections developed in 95% patients. Forty-three patients (75%) died following treatment with daclizumab. The causes of death included active GVHD and infection (79%), active GVHD (5%), chronic GVHD (2%) and relapse (14%). Patients with grade 3-4 GVHD had a significantly shorter median survival than patients with grade 1-2 GVHD (2.0 vs 5.1 months, P=0.001). Daclizumab has no infusion-related toxicity, is active in steroid-refractory GVHD, especially among pediatric patients, but is associated with significant morbidity and mortality due to infectious complications. Careful patient selection and aggressive prophylaxis against viral and fungal infections are recommended.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Drug Resistance , Graft vs Host Disease/drug therapy , Immunoglobulin G/administration & dosage , Acute Disease , Adolescent , Adult , Antibodies, Monoclonal, Humanized , Cause of Death , Child , Child, Preschool , Daclizumab , Drug Evaluation , Female , Follow-Up Studies , Graft vs Host Disease/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infant , Male , Middle Aged , Opportunistic Infections/chemically induced , Retrospective Studies , Steroids/pharmacology , Transplantation, HomologousABSTRACT
Impaired linear growth has been shown to occur in individuals treated during childhood with single-dose and fractionated total body irradiation (TBI) before stem cell transplantation. Our objective was to describe the final heights attained and patient/treatment factors correlating with final height in a cohort of childhood cancer survivors treated with hyperfractionated TBI (total dose 1375 or 1500 cGy). Thirty individuals (18 men) were included in the study. The mean final height standard deviation score (s.d.s.) was -1.9 +/- 0.2, significantly lower than height s.d.s. at TBI (-0.2 +/- 0.2, P < 0.001). Final height s.d.s. was significantly correlated with age at diagnosis, age at TBI and target height (P = 0.04, P < 0.001, P < 0.001, respectively). Treatment with growth hormone (GH) (n = 7) maintained mean height s.d.s. at -2.0 from the onset of GH therapy until attainment of final height. The mean final sitting height s.d.s. was -2.2 +/- 0.2 (n = 16), significantly shorter than mean final standing height s.d.s. (P < 0.01). In conclusion, treatment with hyperfractionated TBI is associated with a reduction in standing height and an even greater reduction in sitting height. Final height after hyperfractionated TBI was similar to that reported after fractionated TBI.
Subject(s)
Body Height , Neoplasms/therapy , Stem Cell Transplantation , Transplantation Conditioning , Whole-Body Irradiation , Adult , Child , Child, Preschool , Female , Growth/radiation effects , Humans , Infant , Male , Neoplasms/radiotherapy , Parents , Patient Selection , Transplantation, Autologous , Transplantation, Homologous , Whole-Body Irradiation/methodsABSTRACT
We report on bloodstream infection (BSI) rates, risk factors, and outcome in a cohort of 298 adult and pediatric hematopoietic stem cell transplantation (HSCT) recipients at Memorial Sloan-Kettering Hospital from September 1999 through June 2003. Methods. Prospective surveillance study. BSI rates are reported per 10,000 HSCT days. Date of engraftment is defined as the first of at least 3 consecutive dates of absolute neutrophil count >500/mm(3) after stem cell infusion. BSI severity grades: severe (intravenous antibiotics), life threatening (sepsis), or fatal (caused or contributed to death). Results. The incidence of pre- and post-engraftment BSI was 22% and 19.5%, respectively. Pre-engraftment highest rates were observed for viridans streptococci (58), Enterobacteriaceae (39), and Enterococcus faecium (34). Post-engraftment rates ranged from 0.2 to 2.9 without any predominant pathogen. In multivariate analyses, pre-engraftment BSI was associated with diagnosis of chronic myelogenous leukemia, age >18 years and peripheral blood stem cell graft; post-engraftment BSI was associated with acute graft-versus-host disease, neutropenia, and liver or kidney dysfunction. Attributable mortality was 12.5% and 1.7% for pre- and post-engraftment BSI, respectively. BSI fatality rates were 24% for viridans streptococci, 8% for E. faecium, 11% for Staphylococcus aureus, and 67% for Candida. Conclusions. Pre-engraftment BSI, especially by viridans streptococci and E. faecium, was associated with substantial attributable mortality. Post-engraftment BSI was a marker of post-transplant complications and rarely the primary cause of death.
Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Sepsis/etiology , Sepsis/mortality , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Risk Factors , Transplantation, Homologous/adverse effectsABSTRACT
PURPOSE: To determine whether cryopreserved solutions of the thrombolytic agent alteplase could be used as a safe, effective, and economically reasonable alternative to urokinase in patients presenting with occluded central venous access devices (CVADs). MATERIALS AND METHODS: Alteplase has been reported as an efficacious alternative to urokinase for treatment of occluded CVADs. However, the practicality of using alteplase as the thrombolytic of choice for this indication remained conjectural. To make this approach economically feasible, alteplase was diluted to 1 mg/mL and 2.5-mL aliquots were stored at -20 degrees C until use. A need to confirm that the cryopreserving and thawing of the reconstituted solution did not compromise the safety and efficacy reported from prior trials was recognized. A quality assessment initiative was undertaken to concurrently monitor the safety and efficacy of this approach. Patients presenting with occluded CVADs received a sufficient volume of the thawed alteplase solution to fill the occluded catheter(s). Data, including efficacy, adverse reactions, dwell time, and catheter type, were collected over a 5-month period. RESULTS: One hundred twenty-one patients accounting for 168 attempted clearances were assessable for safety and efficacy. One hundred thirty-six (81%) of the 168 catheter clearance attempts resulted in successful catheter clearance (95% confidence interval, 74% to 86%). No adverse events were reported. CONCLUSION: Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVADs when stored at -20 degrees C for 30 days. The ability to cryopreserve alteplase aliquots makes it an economically reasonable alternative to urokinase in the setting of CVAD occlusion.
Subject(s)
Catheterization, Central Venous/adverse effects , Cryopreservation/standards , Fibrinolytic Agents/economics , Fibrinolytic Agents/therapeutic use , Tissue Plasminogen Activator/economics , Tissue Plasminogen Activator/therapeutic use , Venous Thrombosis/drug therapy , Adolescent , Adult , Aged , Child , Child, Preschool , Cost-Benefit Analysis , Feasibility Studies , Female , Fibrinolytic Agents/adverse effects , Humans , Infant , Male , Middle Aged , Quality Control , Tissue Plasminogen Activator/adverse effects , United States , Venous Thrombosis/etiologyABSTRACT
Respiratory syncytial virus, one of the most common causes of respiratory infections in immunocompetent individuals, is frequently spread to recipients of HSCT by family members, other patients, and health care workers. In immunosuppressed individuals, progression from upper respiratory tract disease to pneumonia is common, and usually fatal if left untreated. We performed a retrospective analysis of RSV infections in recipients of autologous or allogeneic transplants. The incidence of RSV following allogeneic or autologous HSCT was 5.7% and 1.5%, respectively. Of the 58 patients with an RSV infection, 16 of 21 patients identified within the first post-transplant month, developed pneumonia. Seventy-two percent of patients received aerosolized ribavirin and/or RSV-IGIV, including 23 of 25 patients diagnosed with RSV pneumonia. In this aggressively treated patient population, three patients died of RSV disease, each following an unrelated HSCT.
Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Respiratory Syncytial Virus Infections/etiology , Respiratory Tract Infections/etiology , Adolescent , Adult , Aerosols , Aged , Antiviral Agents/administration & dosage , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppression Therapy/adverse effects , Male , Middle Aged , Pneumonia, Viral/drug therapy , Pneumonia, Viral/etiology , Pneumonia, Viral/therapy , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/therapy , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/therapy , Retrospective Studies , Ribavirin/administration & dosage , Transplantation, Autologous , Transplantation, HomologousABSTRACT
BACKGROUND: Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) and are associated with severe morbidity and mortality. METHODS: We report on four patients who developed chronic, progressive, and irreversible lung disease 1 to 3 years after allogeneic BMT in childhood. These patients had chronic graft-versus-host disease (n=3) or radiation-related pulmonary fibrosis (n=1). Three patients underwent double lung transplants and one patient underwent a single lung transplant 2 to 14 years after BMT. RESULTS: All four patients tolerated the lung transplantation procedure well and showed significant clinical improvement with normalization of pulmonary function tests by 1 year posttransplant. One patient died from infectious complications 3 years after lung transplantation, and one patient died after chronic rejection of the transplanted lungs 6 years posttransplant. Two patients remain alive without significant respiratory impairment 2 and 7 years after lung transplantation. CONCLUSION: We conclude that lung transplantation offers a viable therapeutic option for patients who develop respiratory failure secondary to BMT.
Subject(s)
Bone Marrow Transplantation/adverse effects , Lung Diseases/etiology , Lung Diseases/surgery , Lung Transplantation , Adolescent , Adult , Child , Child, Preschool , Fatal Outcome , Humans , Male , Transplantation, Homologous , Treatment OutcomeABSTRACT
More than 95% of reported cases of disseminated toxoplasmosis following BMT have occurred following an unmodified transplant. Most have been fatal, diagnosed at autopsy and without antemortem institution of specific therapy. From 1989 to 1999, we identified 10 cases of disseminated toxoplasmosis, in 463 consecutive recipients of a T cell-depleted (TCD) BMT. Transplants were from an unrelated donor (n = 5), an HLA-matched sibling (n = 4) or an HLA-mismatched father (n = 1). In 40%, both the donor and recipient had positive IgG titers against T. gondii pre-transplant; in 30%, only the recipient was sero-positive. Three recipients of an unrelated TCD BMT developed toxoplasmosis despite both donor and host testing negative pretransplant. All 10 patients presented with high grade fever. CNS involvement ultimately occurred in seven patients, with refractory respiratory failure and hypotension developing in nine. Eight of 10 cases were found only at autopsy, involving the lungs (n = 7), heart (n = 5), GI tract (n = 5), brain (n = 8), liver and/or spleen (n = 5). The only survivor, treated on the day of presentation with fever and headache, was diagnosed by detection of T. gondii DNA by polymerase chain reaction (PCR) performed on the blood and spinal fluid. This study demonstrates the similar incidence of toxoplasmosis following TCD BMT and that reported post T cell-replete BMT, and underscores the need for rapid diagnostic tests in an effort to improve outcome.
Subject(s)
Bone Marrow Transplantation , Lymphocyte Depletion/adverse effects , T-Lymphocytes/immunology , Toxoplasmosis/etiology , Adult , Female , Humans , Male , Middle Aged , Opportunistic Infections/etiology , Opportunistic Infections/immunology , Toxoplasmosis/immunology , Transplantation, HomologousABSTRACT
We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA), using T cell-depleted two HLA-allele disparate related peripheral blood stem cell transplants (PBSCTs). Patient 1, a 5-year-old male with FA and aplastic anaemia, initially received an HLA two-antigen mismatched unrelated cord blood transplant and failed to engraft. He received fludarabine (Flu) and cyclophosphamide (Cy), followed by a CD34(+) E-rosette(-) (CD34(+)E(-)), T cell-depleted, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCT from his HLA B-DRB1 mismatched father. He received anti-thymocyte globulin (ATG), steroids, FK506 and G-CSF after transplant for rejection and graft-versus-host disease (GVHD) prophylaxis. The patient is now 23 months after SCT with no evidence of GVHD and with full haematopoietic and immune reconstitution. Patient 2, a 10-year-old boy with FA and myelodysplastic syndrome, received single-dose total body irradiation (SDTBI), Flu and Cy followed by a CD34(+)E(-), T-cell-depleted, G-CSF-mobilized PBSCT from his HLA B-DRB1 mismatched sister. He also received ATG, steroids, FK506 and G-CSF after transplant. The patient is now 12 months after SCT in complete remission with no evidence of GVHD. Absolute neutrophil counts (ANC) of > 1 x 10(9)/l were achieved on day 11 and day 10 post transplant respectively. Both patients are fully engrafted. In summary, we report two successful T-cell-depleted stem cell transplants from mismatched related donors for the treatment of Fanconi anaemia, using a fludarabine-based cytoreduction. Both patients experienced minimal toxicity, rapid engraftment and no GVHD.
Subject(s)
Fanconi Anemia/therapy , Hematopoietic Stem Cell Transplantation/methods , Immunosuppressive Agents/therapeutic use , Lymphocyte Depletion/methods , T-Lymphocytes/immunology , Vidarabine/analogs & derivatives , Vidarabine/therapeutic use , Child, Preschool , Cyclophosphamide/therapeutic use , Fanconi Anemia/immunology , Follow-Up Studies , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Recombinant Proteins , Tacrolimus/administration & dosageABSTRACT
Reticular dysgenesis is a rare congenital disorder characterized by severe combined immunodeficiency and profound neutropenia, curable to date, only by bone marrow transplantation. This report describes the association of bilateral sensorineural deafness with this disease.
Subject(s)
Deafness/congenital , Deafness/diagnosis , Leukopenia/congenital , Leukopenia/diagnosis , Lymphatic Diseases/congenital , Lymphatic Diseases/diagnosis , Severe Combined Immunodeficiency/congenital , Severe Combined Immunodeficiency/diagnosis , Thymus Gland , Audiometry , Bone Marrow Transplantation , Evoked Potentials, Auditory, Brain Stem , Female , Histocompatibility Testing , Humans , Incidence , Infant , Infant, Newborn , Leukocyte Count , Leukopenia/blood , Leukopenia/genetics , Leukopenia/therapy , Lymphatic Diseases/blood , Lymphatic Diseases/genetics , Lymphatic Diseases/therapy , Male , Retrospective Studies , Severe Combined Immunodeficiency/blood , Severe Combined Immunodeficiency/genetics , Severe Combined Immunodeficiency/therapyABSTRACT
PURPOSE: A retrospective analysis of the treatment of childhood acute lymphoblastic leukemia (ALL) in second remission (CR2) was undertaken at our institution to compare the outcome and prognostic factors of patients treated with chemotherapy or allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: Seventy-five children who suffered a medullary relapse and achieved a second remission were treated with either an unmodified allogeneic HLA-matched sibling BMT after hyperfractionated total body irradiation (TBI) and cyclophosphamide (n = 38) or chemotherapy according to institutional chemotherapy protocols (n = 37). To avoid the bias of survival from the attainment of second remission in favor of BMT, the final comparative statistical analysis used the landmark approach and comprised 37 and 29 patients from the BMT and chemotherapy groups, respectively RESULTS: The disease-free survival (DFS) rate was 62% and 26% at 5 years, respectively, for the BMT and the chemotherapy groups (P = .03), with relapse rates of 19% and 67%, respectively, for these two groups (P = .01). There was an overall advantage for the BMT therapeutic approach, as compared with chemotherapy, for patients with ALL in CR2 (1) for patients with a WBC count (at diagnosis) of 20 x 10(9)/L or higher (DFS, 40% v 0%) and those with a WBC count of less than 20 x 10(9)/L (DFS, 73% v35%), (2) for patients whose duration of CR1 was less than 24 months (DFS 48% v 9%) and for patients whose duration of CR1 was 24 months or longer (DFS, 81% v 37%) and (3) for patients who were initially treated with intensive regimens incorporating more than five chemotherapy agents (DFS, 57% v 20%) and for patients treated with five agents or fewer (DFS, 72% v 32%). CONCLUSION: In our single-institution series, unmodified HLA-matched allogeneic sibling transplants using hyperfractionated TBI and cyclophosphamide for patients with ALL in CR2 have resulted in superior outcome with a significantly improved probability of DFS and a lower relapse rate, as compared with those for patients treated with chemotherapy, regardless of the duration of first remission, the disease characteristics at diagnosis, or the intensity of prior treatment during first remission.
Subject(s)
Antineoplastic Agents/therapeutic use , Bone Marrow Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Recurrence , Remission Induction , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
The association of an acute reversible encephalopathy with transient occipital lobe abnormalities on imaging studies is well known. This condition has been called reversible posterior leukoencephalopathy syndrome. The clinical presentation usually includes seizures, headache, altered mental status, and blindness, often associated with hypertension and immunosuppressants. The authors discuss a two-year-old male with Down syndrome who presented 2 months after allogeneic bone marrow transplantation with severe oculogyric crisis, without other complaints. The patient was being treated for hypertension and was receiving cyclosporine for prophylaxis of graft-vs-host disease. A computed tomography scan of the head revealed marked bilateral lucencies mainly involving the white matter of the occipital lobes, with a few foci of punctate hemorrhage. The condition improved when cyclosporine was discontinued, but an area of leukomalacia was identified on follow-up magnetic resonance imaging. To the authors' knowledge, oculogyric crisis as a presentation of reversible posterior leukoencephalopathy has not been previously described. Recognizing this association is important, because patients receiving cyclosporine are often receiving other medications that can potentially cause dystonic eye movements, possibly leading to a delay in diagnosis and treatment, which can result in an irreversible neurologic deficit.
Subject(s)
Brain Diseases/diagnosis , Brain Diseases/etiology , Cyclosporine/adverse effects , Hypertension, Malignant/complications , Occipital Lobe/abnormalities , Ocular Motility Disorders/etiology , Bone Marrow Transplantation , Child, Preschool , Chromosomes, Human, Pair 7 , Disease Progression , Humans , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Magnetic Resonance Imaging , Male , Monosomy , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/therapy , Occipital Lobe/pathology , Syndrome , Tomography, X-Ray ComputedABSTRACT
Unrelated bone marrow transplantation (BMT) is often complicated by fatal opportunistic infections. To evaluate features unique to immune reconstitution after unrelated BMT, the lymphoid phenotype, in vitro function, and life-threatening opportunistic infections after unrelated and related T-cell-depleted (TCD) BMT were analyzed longitudinally and compared. The effects of posttransplant donor leukocyte infusions to treat or prevent cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infections on immune reconstitution were also analyzed. This study demonstrates that adult recipients of TCD unrelated BMTs experience prolonged and profound deficiencies of CD3(+), CD4(+), and CD8(+) T-cell populations when compared with pediatric recipients of unrelated BMT and adults after related BMT (P <.01), that these adults have a significantly increased risk of life-threatening opportunistic infections, and that the rate of recovery of CD4 T cells correlates with the risk of developing these infections. Recovery of normal numbers of CD3(+), CD8(+), and CD4(+) T-cell populations is similar in children after related or unrelated BMT. This study also demonstrates that adoptive immunotherapy with small numbers of unirradiated donor leukocytes can be associated with rapid restoration of CD3(+), CD4(+), and CD8(+) T-cell numbers, antigen-specific T-cell responses, and resolution of CMV- and EBV-associated disease after unrelated TCD BMT.