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Biomedical subjects

F Boulad

Publications and source records attributed to F Boulad.

At least 19 recordsLinked to original sources
PubMed1999

Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions.

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.

Adolescent↗
PubMed1999

Posterior leukoencephalopathy syndrome may not be reversible.

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.

Bone Marrow Transplantation↗
PubMed1999

Allogeneic bone marrow transplantation versus chemotherapy for the treatment of childhood acute lymphoblastic leukemia in second remission: a single-institution study.

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.

Antineoplastic Agents↗
PubMed1998

T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease.

Thirty-one consecutive patients with acute myelogenous leukemia (AML) in first complete remission and 8 with AML in second complete remission received T cell-depleted allogeneic bone marrow transplants from HLA-identical sibling donors. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide. Those patients at risk for immune-mediated graft rejection received additional immune suppression with antithymocyte globulin and methylprednisolone in the early peritransplant period. Patients with AML who underwent allogeneic T-cell-depleted bone marrow transplantations (BMT) in first or second remission have achieved respective disease-free survival (DFS) probabilities of 77% (median follow-up at approximately 56 months) and 50% (median follow-up at approximately 48 months). Ten of 31 patients transplanted in first remission were > or = 40 years old and have attained a DFS at 4 years of 70%. For patients with AML transplanted in first or second remission, the respective cause-specific probabilities of relapse were 3.2% or 12.5%, and those of nonleukemic mortality were 19.4% or 37.5%. There were no cases of immune-mediated graft rejection and no cases of grade II to IV acute graft-versus-host disease (GVHD). All survivors enjoy Karnofsky performance scores (KPS) of 100%, except 2 patients with KPS of 80% to 90%. T-cell-depleted allogeneic BMT can provide durable DFS together with an excellent performance status in the majority of patients with de novo AML. In addition, GVHD is not an obligatory correlate of the graft-versus-leukemia benefit or freedom from relapse afforded by allogeneic BMT administered as postremission therapy for AML. This study provides a basis for prospective comparison with other postremission therapies considered standard in the management of patients with this disease.

Adolescent↗
PubMed1998

High-dose induction chemoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy in rhabdomyosarcoma, extraosseous Ewing's sarcoma, and undifferentiated sarcoma.

PURPOSE: To improve response and survival rates in patients with high-risk rhabdomyosarcoma (RMS), extraosseous Ewing's sarcoma, and undifferentiated sarcoma, we used a short course of induction with multi-agent chemotherapy, hyperfractionated radiotherapy, and surgery when possible. Consolidation was with intensive chemotherapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Twenty-six patients (21 with RMS, three with undifferentiated sarcoma, and two with extraosseous Ewing's sarcoma) were entered onto the protocol between June 1990 and March 1994. Induction consisted of ifosfamide, etoposide, doxorubicin, dactinomycin, cyclophosphomide, and vincristine, and a split course of hyperfractionated radiotherapy. Patients who attained a complete response (CR) or good partial response (GPR) received consolidation with high-dose melphalan and etoposide followed by ABMT. RESULTS: Of 26 previously untreated patients 19 (73%) achieved a CR (n=13) or GPR (n=6) at the completion of induction and underwent ABMT. Two-year overall survival (OS) was 56% (95% confidence interval [CI], 36% to 76%) and progression-free survival (PFS) was 53% for the whole group (95% CI, 33% to 73%). CONCLUSION: Consolidation of response by myeloablative chemotherapy was well tolerated. Split-course hyperfractionated radiotherapy did not increase the rate of local control. The results of this short-course therapy were comparable to previous therapies of 1 to 2 years' duration. Induction and consolidation chemotherapy, as well as radiation dose, could be further intensified, since no death due to toxicity occurred among these patients.

Adolescent↗
PubMed1997

Gonadal function after bone marrow transplantation for acute leukemia during childhood.

OBJECTIVE: To examine the impact of bone marrow transplantation (BMT), using high-dose chemotherapy and hyperfractionated total body irradiation, on gonadal function in survivors of acute leukemia treated during childhood. STUDY DESIGN: We conducted a retrospective study of 33 subjects (17 boys) who underwent a BMT for acute leukemia (acute lymphoblastic leukemia, n = 20; acute myelogenous leukemia, n = 13) at a single institution. All patients were prepubertal at the time of BMT (median age, 7.1 years (3.7 to 11.6 years)); at the time of their last examination the boys were a median of 14 years (10.4 to 17.1 years) of age and the girls were a median of 16.9 years (9.5 to 21.9 years) of age. RESULTS: Of 17 boys, 14 (82%) entered puberty spontaneously and 13 demonstrated age-appropriate plasma concentrations of testosterone. Two boys (aged 10.5 and 11 years) remain clinically and hormonally prepubertal, and one boy has overt Leydig cell failure requiring androgen replacement therapy. Thirty-six percent of pubertal boys have elevated plasma concentrations of luteinizing hormone and 64% have raised levels of follicle-stimulating hormone. Boys with increased levels of luteinizing hormone were significantly younger at BMT (5.4 +/- 0.8 vs 7.8 +/- 0.8 years; p = 0.024). Of 16 girls, 9 (56%) had spontaneous puberty with onset of menarche at a median age of 13 years (9.5 to 15.8 years). Though six (67%) of these nine girls have had increased plasma concentrations of luteinizing and follicle-stimulating hormones, normalization has occurred in two during a period of 4 to 7 years. The remaining seven subjects required hormone replacement because of clinical and biochemical evidence of ovarian failure. One of these subjects has recovered ovarian function after 5 1/2 years. Female patients with ovarian failure were significantly older at BMT compared with female patients with spontaneous puberty/menarche (8.6 +/- 23 years vs 6.1 +/- 1.8; p = 0.03). CONCLUSION: Our results indicate that most prepubertal boys undergoing BMT with chemotherapy and hyperfractionated total body irradiation can expect to enter and progress normally through puberty. For prepubertal girls treated with these regimens, at least 50% retain adequate ovarian function to enter puberty and menstruate regularly.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Risk of extramedullary relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia with leukemia cutis.

Leukemia cutis (LC) is a rare feature of acute myeloblastic leukemia (AML). Little information is available regarding its prognostic influence on post-transplant outcome. In our institution, 202 patients with AML received an allogeneic HLA-identical marrow transplant from related donors between March 1982 and January 1994. Thirteen patients had prior leukemic involvement of the skin (leukemia cutis or LC group) while 189 patients did not (non-LC group). There was a higher incidence of patients with the M4-M5 FAB subtypes in the LC group (83%) as compared to the non-LC group (33%). In addition, the percentage of patients transplanted in relapse was also higher in the LC group (69 vs 15%). While there were no differences observed in the rates of relapse post-transplant in the LC and non-LC groups when matched for stage of disease at transplant, the sites of relapse differed markedly. Five of six relapses in the LC group involved extramedullary sites as compared to only six of 38 relapses in the non-LC group (P = 0.002), with a 6-year probability of extramedullary relapse of 38.5% in the LC group as compared to 3.9% in the non-LC group. This increased probability of extramedullary relapse was independent of the FAB morphology (50 vs 2% for patients with the M4-M5 subtypes in the LC and the non-LC group respectively) and of disease status at the time of transplant. Moreover, only three relapses post-transplant involved the skin, all of which were in the LC group, with a probability of skin relapse of 23.1% in this group. Patients with AML and leukemia cutis have a remarkable propensity to relapse in extramedullary sites following marrow transplantation. These relapses occur in the skin as well as other organs. Further investigations are needed to understand the biological basis of this clinical feature.

Adult↗
PubMed1997

Comparison of long-term outcome of children with severe aplastic anemia treated with immunosuppression versus bone marrow transplantation.

Children with severe aplastic anemia (SAA) are treated with bone marrow transplantation (BMT) if a human leukocyte antigen (HLA) compatible sibling donor is available, or alternatively with immunosuppressive therapy (IST). Three retrospective trials examining BMT vs IST in pediatric patients treated from 1970-1988 found BMT resulted in a superior survival rate. Advances have been made in general supportive care and in the approach to each of these treatment modalities in the last decade. To compare survival following BMT and IST in a more recent era, we retrospectively analyzed the results of 48 consecutively treated children with SAA presenting to Memorial Sloan-Kettering Cancer Center (MSKCC) between 1983 and 1992. In contrast to the previous studies, the estimated survival of the BMT and IST groups at 120 months are equivalent, 75.6% and 73.8%, respectively. The IST results in our series are superior to the 42-48% (2-10 year) survival previously published, but similar to survival data observed in more recent IST trials employing more intensive immunosuppression (antithymocyte globulin and cyclosporine). The overall BMT survival rates are similar to those previously published, although BMT results improved dramatically during the latter five years of this analysis, with all 11 patients transplanted surviving with a minimum follow-up of 3 years. No surviving BMT patient has extensive chronic graft-versus-host disease (GvHD), a major cause of long-term mortality post-BMT. Therefore, it is likely the BMT survival curve will remain stable. In contrast, the survival curve of the IST patients is likely unstable, since patients are still at risk for relapse or development of clonal disease. Thus, despite overall similar survival rates, we continue to recommend BMT as first-line therapy in pediatric SAA patients with matched sibling donors.

Adolescent↗
PubMed1996

Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy.

PURPOSE: To test intensive alkylator-based therapy in desmoplastic small round-cell tumor (DSRCT). PATIENTS AND METHODS: Patients received the P6 protocol, which has seven courses of chemotherapy. Courses 1, 2, 3, and 6 included cyclophosphamide 4,200 mg/m2, doxorubicin 75 mg/m2, and vincristine (HD-CAV). Courses 4, 5, and 7 consisted of ifosfamide 9 g/m2 and etoposide 500 mg/m2 for previously untreated patients, or ifosfamide 12 g/m2 and etoposide 1,000 mg/m2 for previously treated patients. Courses started after neutrophil counts reached 500/microL and platelet counts reached 100,000/microL. Tumor resection was attempted. Post-P6 treatment options included radiotherapy and a myeloablative regimen of thiotepa (900 mg/m2) plus carboplatin (1,500 mg/m2), with stem-cell rescue. RESULTS: Ten previously untreated and two previously treated patients have completed therapy. The male-to-female ratio was 11:1. Ages were 7 to 22 years (median, 14). The largest masses were infradiaphragmatic (n = 11) or intrathoracic (n = 1). Other findings included serosal implants (n = 11), regional lymph node invasion (n = 8), ascites or pleural effusion (n = 7), and metastases to liver (n = 5), lungs (n = 4), distant lymph nodes (n = 3), spleen (n = 2), and skeleton (n = 2). Tumors uniformly responded to HD-CAV, but there were no complete pathologic responses. One patient died at 1 month from tumor-related Budd-Chiari syndrome. Of seven patients who achieved a complete remission (CR), five remain in CR 9, 12, 13, 33, and 38 months from the start of P6, one patient died of infection at 12 months (autopsy-confirmed CR), and one patient relapsed 4 months off therapy. Of four patients who achieved a partial remission (PR), one remains progression-free at 34 months and three developed progressive disease. Five patients received local radiotherapy: three were not assessable for response, but in two patients, antitumor effect was evident. Four patients received thiotepa/carboplatin: two were in CR and remain so, and two patients had measurable disease that did not respond. CONCLUSION: For control of DSRCT, our experience supports intensive use of HD-CAV, aggressive surgery to resect visible disease, radiotherapy to high-risk sites, and myeloablative chemotherapy with stem-cell rescue in selected cases.

Abdominal Neoplasms↗
PubMed1995

Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease.

Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions in patients with chronic myeloid leukemia (CML) who relapse after marrow transplantation. We wanted to determine if substantially lower numbers of donor leukocytes could induce remissions and, if so, whether this would reduce the 90% incidence of graft-versus-host disease (GVHD) associated with this therapy. Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each patient received escalating doses of donor leukocytes at 4- to 33-week intervals. Leukocyte doses were calculated as T cells per kilogram of recipient weight. There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific chimerism and residual leukemia detection were assessed using sensitive polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients achieved remission. Remissions were achieved at the following T-cell doses: 1 x 10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The incidence of GVHD was correlated with the dose of T cells administered. Only 1 of the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed GVHD, whereas this complication developed in 8 of the 11 responders who received a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1 secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment became full donor T-cell chimeras at the time of remission. Donor leukocytes with a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism together with a potent graft-versus-leukemia (GVL) effect. The dose of donor leukocytes or T cells used may be important in determining both the GVL response and the incidence of GVHD. In many patients, this potent GVL effect can occur in the absence of clinical GVHD.

Adolescent↗
PubMed1995

Growth in children after bone marrow transplantation for acute leukemia.

We evaluated the growth of children with acute leukemia who received a bone marrow transplant (BMT) after preparation with hyperfractionated total body irradiation (TBI). Seventy-two patients (27 female and 45 male patients) with acute lymphoblastic leukemia (ALL; n = 39) or acute myelogenous leukemia (AML; n = 33) who were less than 14 years of age at BMT were studied. Before BMT all had received multiagent chemotherapy and 31 had received cranial irradiation (RT). Preparation for BMT included total body irradiation (1,375 cGy [n = 37] or 1,500 cGy [n = 35]). Heights, expressed as standard deviation scores (SDS), were studied up to 4 years post-BMT. The estimated height SDS for the entire group at the time of BMT was -0.28 +/- 0.05 and decreased to -1.11 +/- 0.22 at 4 years post-BMT (P < .0001). Using a growth curve model to compare covariate groups over the period of study, we found that the loss in height SDS was most significant in those patients who received cranial RT before BMT (P = .005). The estimated height SDS for patients treated with cranial RT went from -0.52 +/- 0.20 at transplantation to -1.83 +/- 0.23 4 years later. In contrast, patients who did not receive cranial RT before BMT showed a smaller decrease in height SDS over the 4-year observation period, ie, -0.11 +/- 0.20 decreasing to -0.73 +/- 0.21. Similarly, patients with a diagnosis of ALL had a greater loss of height SDS than those with AML (P = .033). Fifteen of 18 patients tested were found to be growth hormone (GH) deficient; 9 patients were treated with GH and all showed an improvement in growth velocity (P < .0001). We conclude that (1) children with acute leukemia who have received cranial RT and subsequently undergo BMT, primarily those with ALL, are at high risk for growth failure and GH deficiency, and (2) that fractionation of TBI may have a relative sparing effect on growth.

Acute Disease↗
PubMed1995

Thyroid dysfunction following bone marrow transplantation using hyperfractionated radiation.

Thyroid dysfunction has been reported following single dose and fractionated radiation in the context of bone marrow transplantation (BMT). Limited data are available regarding this complication following hyperfractionated radiation. We undertook a retrospective analysis of thyroid function in 150 patients who received BMT at our institution, and who were alive and disease-free for at least 1 year after transplant. There were 100 pediatric patients and 50 adult patients, with a median follow-up of 6.2 years for the whole group. These patients had acute (n = 91) or chronic leukemias (n = 36), severe aplastic anemia (n = 18) or immunodeficiency disorders (n = 5). The majority of the patients received radiation-based cytoreductive regimens including 129 patients who received hyperfractionated total body irradiation (TBI) to a total dose of 1375 cGy or 1500 cGy and 10 patients who received total lymphoid irradiation (TLI) to a total dose of 600 cGy. Twenty two patients of the cohort of 150 patients (14.7%) and 21 of the 139 patients (15.1%) who received hyperfractionated radiation were found to have developed hypothyroidism, 11-88 months after transplant (median 49 months). Eight patients had received 1375 cGy and 12 patients 1500 cGy TBI, while one patient was treated with 600 cGy TLI and one patient was treated with chemotherapy only (busulfan and cyclophosphamide). Three patients had primary thyroid failure with an elevated TSH and a low T4 index, while 19 patients had compensated hypothyroidism with an elevated TSH but a normal T4 index. Six of eight patients with untreated compensated hypothyroidism recovered spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Hyperfractionated total lymphoid irradiation and cyclophosphamide for preparation of previously transfused patients undergoing HLA-identical marrow transplantation for severe aplastic anemia.

PURPOSE: To assess the immunosuppressive capacity of hyperfractionated total lymphoid irradiation and cyclophosphamide for transplantation of unmodified allogeneic marrow in sensitized aplastic anemia patients. METHODS AND MATERIALS: From February 1983 to September 1990, 23 multiply transfused aplastic anemia patients underwent unmodified bone marrow transplantation from HLA genotypically identical sibling donors following preparation with 6 Gy hyperfractionated total lymphoid irradiation and 160 mg/kg cyclophosphamide. Graft-versus-host disease prophylaxis included steroids in one patient, methotrexate in four, cyclosporine in seven, and methotrexate/cyclosporine in 12. There were 17 males and 6 females with a median age of 13 (range: 2.5-32). RESULTS: One patient died early before engraftment of bacterial sepsis. Twenty-two patients were evaluable for engraftment. Three experienced graft failure including one primary, and two late graft failures associated with cyclosporine withdrawal. Acute graft-versus-host disease occurred in 7/22 (> or = grade II in 6), and chronic graft-versus-host disease in 3/17 patients. Except for a patient who received total body irradiation for a second transplant, no patient in this series developed interstitial pneumonia. Fifteen patients are alive with follow-up of 38-125 months (median 68). The overall actuarial survival at 5 years is 69%, at 8 years it is 60%, with one late death. The survival of adult patients was similar to that of younger patients (> or = 16 years old: 63%, < 16 years old: 55%). The development of acute graft-versus-host disease adversely influenced survival (88% with Grade 0-I, 17% with grade II-IV; p = 0.002). No hypothyroidism or secondary malignancies have been documented in this series. CONCLUSION: Pretransplant immunosuppression with 6 Gy of hyperfractionated total lymphoid irradiation and 160 mg/kg CY reduces but does not eliminate the incidence of graft failure in sensitized aplastic anemia patients. The dose and the mode of administration of total lymphoid irradiation in this trial may be associated with a lower incidence of late side effects. Survival is comparable to that obtained using preparative regimens without radiation.

Adolescent↗
PubMed1994

Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation.

BACKGROUND: Lymphoma associated with Epstein-Barr virus (EBV) is a complication of bone marrow transplantation that responds poorly to standard forms of therapy. The lymphoma is usually of donor origin. We hypothesized that treatment with infusions of donor leukocytes, which contain cytotoxic T cells presensitized to EBV, might be an effective treatment. METHODS: We studied five patients in whom EBV-associated lymphoproliferative disorders developed after they received a T-cell-depleted allogeneic bone marrow transplant. Biopsy specimens were immunophenotyped, subjected to the polymerase chain reaction to determine the origin of the lymphoma (donor or host) and to detect the presence of EBV, and analyzed by Southern blotting for the presence of the clonal EBV genome and immunoglobulin-gene rearrangement. Patients were treated with infusions of unirradiated donor leukocytes at doses calculated to provide approximately 1.0 x 10(6) CD3+ T cells per kilogram of body weight. RESULTS: Histopathological examination of biopsy specimens from all five patients demonstrated monomorphic, malignant lymphomas of B-cell origin. Each of the four specimens that could be evaluated was of donor-cell origin. Evidence of clonality was found in two of the three samples adequate for study. EBV DNA was detected by the polymerase chain reaction in all five samples. In all five patients there were complete pathological or clinical responses. The responses were first documented histologically within 8 to 21 days after infusion. Clinical remissions were achieved within 14 to 30 days after the infusions and were sustained without further therapy in the three surviving patients for 10, 16, and 16 months. CONCLUSIONS: In a small number of patients, infusions of unirradiated donor leukocytes were an effective treatment for EBV-associated lymphoproliferative disease that arose after allogeneic bone marrow transplantation.

Adult↗
PubMed1994

Lactic acidosis and renal enlargement at diagnosis and relapse of acute lymphoblastic leukemia.

Bilateral renal enlargement was noted on ultrasonography during an extensive renal evaluation for severe hypokalemic metabolic acidosis with an increased anion gap in a 12-year-old Hispanic boy who had normal results of a physical examination and complete blood count. The patient was found to have acute lymphoblastic leukemia. Resolution of the lactic acidosis and bilateral renal enlargement occurred with initiation of chemotherapy and recurred with each subsequent relapse.

Acidosis, Lactic↗