Non-malignant Hematological Diseases Research Articles

Allogeneic Peripheral Blood Stem Cell Transplantation. Safety, Hematologic Recovery, Kinetics, and Complications

Background Hematopoietic stem cell transplants are an accepted treatment for several malignant and nonmalignant hematologic diseases. Recently, the peripheral blood, after mobilization of stem cells with growth factors, has become the source of choice for hematopoietic stem cells. We report on a series of patients who received peripheral blood stem cell transplants at the Instituto Nacional de Cancerologia (INCAN) in Mexico City. Methods Between May 1995 and December 1999, 33 patients received peripheral blood stem cell transplants to treat hematologic diseases. Sixty percent of our patients had chronic myelocytic leukemia (CML). All had a matched related donor. Patients were conditioned with one of five different conditioning regimens and subsequently received one of two different graft-vs.-host disease prophylaxis regimens. Stratified Wilcoxon rank-sum, chi square, and Mann-Whitney tests were used to analyze the results. Results In our series, median time to achieve a total neutrophil count of 0.5 × 10 9/L was 14 days and to achieve a platelet count of 20 × 10 9/L, 15 days. Acute graft-vs.-host disease occurred in seven patients. Chronic graft-vs.-host disease occurred in 69% of surviving patients. Survival for low-risk patients was 67% and for the high-risk group, 9%. Conclusions Peripheral blood stem cells produce a faster hematopoietic recovery. The rate of acute graft-vs.-host disease is not increased using the peripheral blood as source of stem cells; however, chronic graft-vs.-host disease continues to be a significant problem. Donors tolerated the procurement procedure without complications.

HLA-identical sibling peripheral blood stem cell transplantation in children and adolescents.

Allogeneic peripheral blood stem cell transplantation (PBSCT) was performed in children and adolescents for the treatment of malignant (n = 49) and nonmalignant hematological disease (n = 8). Granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCs were apheresed from 57 HLA-matched siblings aged 9 months to 24 years (median, 8 years) without any serious adverse, effects. No abnormalities were found in these donors for a median follow-up of 25 months (range, 6-56 months). Patients were conditioned with a TBI-containing regimen (n = 17) or a non-TBI regimen (n = 40). GVHD prophylaxis consisted of methotrexate (MTX) plus cyclosporine A (CSP) for 23 patients, CSP plus methylprednisolone (mPDN) for 22 patients, MTX only for 7 patients, CSP only for 4 patients, and MTX plus CSP plus mPDN for 1 patient. Engraftment was prompt, with a median number of days to reach an absolute neutrophil count (ANC) above 0.5 x 10(9)/L of 13 days (range, 8-23 days), with 1 graft failure. Acute GVHD (grades II-IV) occurred in 8 (16%) of 49 evaluable patients, and chronic GVHD developed in 23 (64%) of 36 evaluable patients. Notably, two thirds of chronic GVHD was extensive. The Kaplan-Meier estimate of 3-year disease-free survival was 0% for refractory disease (n = 6), 37.2% +/- 11.8% for high-risk malignancies (n = 25), 81.4% +/- 9.7% for standard-risk malignancies (n = 18), and 100% for nonmalignant disease (n = 8). The estimated 100-day nonrelapse mortality rate was 9.9% +/- 4.2%. In conclusion, allogeneic PBSCT is feasible in a pediatric population. Although the grade of acute GVHD was set low, as in Japanese BMT studies, the incidence and severity of chronic GVHD appears to be relatively high. For nonmalignant disease, the question arises of whether the higher incidence and severity of chronic GVHD is a drawback of this procedure. For high-risk malignancies, whether or not a graft-versus-leukemia effect prevents relapse needs to be clarified in future comparative studies with BMT.

Allogeneic CD34+ -selected peripheral stem cell transplantation from parental donors in children with non-malignant diseases.

Allogeneic peripheral stem cell transplantation in six children with non-malignant hematologic or metabolic diseases which are eventually fatal was carried out with parental donors. Given three to five HLA mismatches, all grafts underwent CD34+ cell selection as graft-versus-host prophylaxis. The patients received median doses of 16.7 x 10(6) CD34+ cells/kg and 1.2 x 10(4) CD3+ cells/kg. All transplants engrafted. Neutrophils >0.5/nl were reached on day 11 (9-19) and platelets >50/nl on day 13 (10-25). Acute GVHD responding to steriods occured in three of six patients; it was restricted to the skin and overall did not exceed grade I. Two patients died of viral infections and four are alive with stable blood counts for 13, 15, 25 and 26 months. For children with non-malignant diseases which will eventually be fatal and which can be cured or ameliorated by allogeneic BMT, CD34+-selected stem cell transplants from mismatched or even haploidentical parents can be used if no other suitable donor is available. With high CD34+ cell doses and low CD3+ cell numbers, engraftment and avoidance of acute GVHD can be expected. Infections after transplantation remain the primary threat to survival.

Infectious complications within the first year after nonmyeloablative allogeneic peripheral blood stem cell transplantation.

Nonmyeloablative peripheral blood stem cell transplantation (PBSCT) is a novel therapeutic strategy for patients with malignant and non-malignant hematologic diseases. Infectious complications of this procedure have not been previously well described. Data on 12 patients transplanted at a tertiary care center were collected prospectively and verified retrospectively. Neutropenia developed in a third of patients, lasting for a median of 5 days. All patients developed some degree of graft-versus-host disease, as intended. Most patients achieved full chimerism by week 5. Bacterial infections occurred in two patients (17%). Cytomegalovirus (CMV) viremia occurred in five patients (42%) at a median of 80 days; none had received CMV prophylaxis. Viremia was associated with fever and fatigue in three patients, possible gastrointestinal involvement in one patient and was asymptomatic in one patient. All viremic patients responded to intravenous ganciclovir therapy. No fungal infections were documented. No patients died as a result of infection. The incidence of CMV viremia in our patients was high, but the incidence of invasive disease due to CMV was low. The best strategy to prevent CMV in patients undergoing nonmyeloablative PBSCT remains to be determined, but strategies employed in traditional allogeneic bone marrow transplantation should be considered in these patients.

Hepatitis C virus infection and lymphoproliferative diseases: prospective study on 1,576 patients in France.

Discordant data have been reported about the prevalence of hepatitis C virus (HCV) infection in patients with lymphoproliferative diseases and the putative role of HCV in lymphomagenesis. To assess the prevalence of HCV infection in patients admitted to a hematology department in Paris, France. Prospective, controlled study. University medical center. 813 patients admitted to the Hematology department (164 B-cell non-Hodgkin's lymphoma, 34 Hodgkin's diseases, 107 chronic lymphocytic leukemia, 54 multiple myeloma, 12 Waldenström's macroglobulinemia, 17 acute lymphoblastic leukemia, 6 hairy cell leukemia, 189 myeloproliferative diseases, 6 solid organ tumors, and 224 nonmalignant diseases) and 694 patients admitted to the Internal Medicine department (control group). All patients were tested for antibodies to HCV by a third-generation enzyme-linked immunosorbent assay. HCV antibodies were detected in 20 of 813 (2.46%) patients in Hematology including 11 of 394 (2.79%) patients with lymphoproliferative diseases, 3 of 164 (1.83%) B-cell non-Hodgkin's lymphoma, 2 of 107 (1.87%) chronic lymphocytic leukemia, 1 of 54 (1.85%) multiple myeloma, 1 of 189 (0.5%) myeloproliferative diseases, and 8 of 224 (3.57%) nonmalignant hematologic diseases. HCV antibodies were detected in 3 of 694 (0.43%) patients in the control group. HCV contamination preceded B-cell non-Hodgkin's lymphoma only in 2 of 3 HCV-positive patients. The prevalence of HCV infection was low (1.83%) in patients with B-cell non-Hodgkin lymphoma. HCV seems not to play a major role in the pathogenesis of B-cell lymphoma in France. Cofactors should be stressed to explain geographical discrepancies.

History of development in the transplantation of hematopoietic stem cell

Some malignant and nonmalignant hematological diseases can be cured by the transplantation of allogeneic stem cell. It is thought to be one of the landmarks in the development of modern medicine. Hematopoietic stem cell transplantation has been performed for about one hundred years in the phases of germination, early investigation and development. The great challenge now is how to perfect the technique and to extend the applied areas.

Nonmyeloablative allogeneic stem cell transplantation: early promise and limitations.

Allogeneic stem cell transplantation is used to treat a variety of malignant and nonmalignant hematologic diseases. Conventionally, high-dose chemoradiotherapy-based preparative regimens were considered essential both for tumor eradication and facilitation of donor stem cell engraftment. It is now apparent that an immune-mediated graft-versus-tumor effect has a pivotal role in the curative potential of allogeneic stem cell transplantation. This has prompted the development of less toxic, nonmyeloablative but profoundly immunosuppressive preparative regimens, often fludarabine- or radiation-based. Full donor engraftment can be achieved; however, a significant number of patients achieve a mixed chimeric state. Mixed hematopoietic chimerism provides a platform for the use of adoptive immunotherapy using donor lymphocyte infusions to maximize the immune-mediated antitumor effect, but the optimal usage has yet to be determined. Immediate procedure-related mortality with nonmyeloablative regimens has been low, but graft-versus-host disease remains a major clinical concern and treatment challenge. Major tumor responses have been seen in many hematologic malignancies primarily including patients with highly chemorefractory disease. Follow-up data have been short and additional time is needed to determine the efficacy and toxicities of this immunotherapy. This approach has potential for widespread clinical application including HLA mismatched and matched unrelated donor transplantation, exploration of a graft-versus-solid tumor effect, and correction of phenotypic expression in nonmalignant disorders.

Non-myeloablative stem cell transplantation (Nst) For the treatment of malignant and non-malignant diseases

Abstract We have developed non-myeloablative stem cell transplantation (NST), using Fludarabine-based regimen (30 mg/m 2 /day × 6) in conjunction with either oral Busulfan (4 mg/Kg/day × 2) or higher doses in children due to rapid pharmakotinetics; Cytoxan (5 mg/Kg/day × 2) in Fanconi's anemia or 60 mg/Kg × 2 in severe aplastic anemia with ATG (fresenius) (5 to 10 mg/Kg/day × 4) or using single low dose total body irradiation (TBI) 200 cGY. Included were patients with hematologic malignancies (acute & chronic leukemia, lymphoma, MDS) and patients with non-malignant hematologic disease (aplastic anemia, Fanconi's anemia, Gauchers', osteopetrosis, chronic granulomatosis disease, Thalassemia major and Diamond Blackfand Syndrome). NST was also tried in a cohort of 16 patients with matched unrelated donor, as well as in 11 patients who failed prior myeloablative stem cell transplantation. Engraftment was observed in all patients with a matched donor available with minimal or no aplasia. Procedure-related toxicity and mortality was low, but GVHD was still the single major problem. The clinical outcome of patients belonging to all NST subgroups will be updated. The data suggest that following induction of host vs graft tolerance, donor immunocompetent cells can displace and replace host with donor immunohematopoietic cells. NST may become the treatment of choice for patients in need of allogeneic stem cell transplantation for malignant and non-malignant diseases.

Mixed chimerism and tolerance without whole body irradiation in a large animal model.

Mixed hematopoietic chimerism may provide a treatment for patients with nonmalignant hematologic diseases, and may tolerize patients to organ allografts without requiring chronic immunosuppression. However, the toxicity of the usual conditioning regimens has limited the clinical applicability of this approach. These regimens generally include some level of whole body irradiation (WBI), which is thought to facilitate engraftment either by making room for donor hematopoietic stem cells or by providing sufficient host immunosuppression to enable donor cells to engraft. Here, we have established mixed chimerism across both minor and major histocompatibility barriers in swine, by using high doses of peripheral blood stem cells in the absence of WBI. After mixed chimerism was established, swine leukocyte antigen-matched (SLA-matched) donor skin grafts were tolerated and maintained for a prolonged period, whereas third-party SLA-matched skin was rejected promptly. Donor-matched kidney allografts were also accepted without additional immunosuppression. Because of its low toxicity, this approach has potential for a wide range of clinical applications. Our data may indicate that niches for engrafting stem cells are filled by mass action and that WBI, which serves to empty some of these niches, can be omitted if the donor inoculum is sufficiently large and if adequate host T-cell depletion is achieved before transplant.

Follow-up of chimerism in children with hematological diseases after allogeneic hematopoietic progenitor cell transplants.

Using in situ hybridization with an X and Y chromosome probe mixture, 106 bone marrow samples from 38 patients with malignant and non-malignant hematological diseases who received sex-mismatched allogeneic hematopoietic progenitor cell transplants (PCT) in a single institution within short-term intervals (1, 3, 6, 12, 24 and >24 months) have been sequentially studied. The patients received either HLA-identical (n = 31) or non-identical (n = 7) PCT. Twenty-six children showed donor chimerism, 10 children showed mixed chimerism (MC) and two children presented autologous reconstitution. Chimerism status with different parameters has been related (age, sex, donor, disease status before PCT, conditioning regimen, GVHD prophylaxis, relapse, GVHD and survival). Our results indicate that female patients (P = 0.011) and a less intensive conditioning regimen (P = 0.039) are significantly associated with the MC status. Mixed chimerism is not, per se, significantly associated with leukemia relapse but an increase of the MC is indicative of clinical relapse.

Mixed hematopoietic chimerism after marrow allografts. Transplantation in the ambulatory care setting.

This paper describes the development of nonmyeloablative marrow transplant programs that have little toxicity in a canine model and their translation to patients with malignant and nonmalignant hematological diseases.

Expression of Membrane-Associated Macrophage Colony-Stimulating Factor (M-CSF) in Hodgkin's Disease and Other Hematologic Malignancies

We have identified a membrane-bound form of M-CSF (m-M-CSF) from an established human leukemic J6-1 cell line. To further understand its biological significance, we studied the expression of this membrane-associated growth factor in the lymph nodes of lymphoma patients and bone marrow smears from patients with hematologic diseases by immunohis-tochemical staining using anti-M-CSF MAb. We detected a high incidence of m-M-CSF expression in 75% (9/12) of the lymph node sections from patients with Hodgkin's Disease (HD). The antigens were detected primarily in large clusters of mononuclear Hodgkin's cells and the extracellular matrix (EM) surrounding them. In one HD patient with abundant multinucleated Reed-Sternberg (R-S) cells, all of them were intensely stained with anti-M-CSF MAb. In non-Hodgkin's lymphomas (NHL), the incidence (17.6%) of m-M-CSF expression was lower (3/17). Yet, no m-M-CSF antigens were detected in the lymph nodes from six cases of non-hematologic malignancies and other diseases. A high response also was detected in bone marrow smears obtained from patients with hematologic malignancies, which include myeloid leukemias (32.5%), lymphomas with bone marrow metastasis (50%) and myelodysplastic syndromes (MDS) (37.5%). By comparison, only 6.8% of bone marrow smears from non-malignant hematologic diseases and 2.7% of lymphoid leukemias showed positive staining with anti-M-CSF MAb. Our results showed that high expression of m-M-CSF antigens is linked to some types of lymphomas, especially HD. and myeloid leukemias, and may play a role in the development of these hematologic malignancies.

Increase in height during the first year after bone marrow transplantation reflecting nutritional status of children.

We studied the influence of pre-transplant nutritional status on height velocity during the first post-transplant year. Thirty-seven children aged 1.4-12.4 years, 19 males and 18 females, underwent bone marrow transplantation (24 allogeneic, 13 autologous) with fractionated total body irradiation included in the preparative regimen of 25. The underlying diagnoses were leukemia (n = 16), malignant solid tumor (n = 11), and non-malignant hematologic or metabolic disease (n = 10). The serum concentrations of albumin, pre-albumin and transferrin were measured. Anthropometric measurements included weight, mid-arm circumference (MAC) and triceps skinfold thickness, expressed as percentages of the age- and sex-specific standards. The skeletal muscle protein reserve was estimated as muscle index (MI) by ultrasonographic imaging of the femoral quadriceps muscle. Height velocity was expressed as a standard deviation score (SDS) of the age- and sex-specific mean. The mean relative height velocity SDS was -1.6 (95% CI -2.2- -1.0). Height velocity correlated significantly with pre-transplant MI (r = 0.54, P = 0.004), concentration of serum transferrin (r = 0.33, P = 0.05) and MAC (r =0.45, P = 0.04). Our data suggest that pre-transplant nutritional status has an impact on growth in height during the post-transplant period.

Nonmyeloablative Stem Cell Transplantation and Cell Therapy as an Alternative to Conventional Bone Marrow Transplantation With Lethal Cytoreduction for the Treatment of Malignant and Nonmalignant Hematologic Diseases

AbstractMyeloablative conditioning associated with hazardous immediate and late complications is considered as a mandatory first step in preparation for allogeneic blood or marrow transplantation (allogeneic BMT) for the treatment of malignant hematologic disorders and genetic diseases. Immune-mediated graft-versus-leukemia (GVL) effects constitute the major benefit of allogeneic BMT. Therefore, we have introduced the use of relatively nonmyeloablative conditioning before allogeneic BMT aiming for establishing host-versus-graft tolerance for engraftment of donor immunohematopoietic cells for induction of GVL effects to displace residual malignant or genetically abnormal host cells. Our preliminary data in 26 patients with standard indications for allogeneic BMT, including acute leukemia (n = 10); chronic leukemia (n = 8), non-Hodgkin's lymphoma (n = 2), myelodysplastic syndrome (n = 1), multiple myeloma (n = 1), and genetic diseases (n = 4) suggest that nonmyeloablative conditioning including fludarabine, anti–T-lymphocyte globulin, and low-dose busulfan (8 mg/kg) is extremely well tolerated, with no severe procedure-related toxicity. Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose of cyclosporin A as the sole anti-graft-versus-host disease (GVHD) prophylaxis resulted in stable partial (n = 9) or complete (n = 17) chimerism. In 9 patients absolute neutrophil count (ANC) did not decrease to below 0.1 × 109/L whereas 2 patients never experienced ANC <0.5 × 109/L. ANC ≥ 0.5 × 109/L was accomplished within 10 to 32 (median, 15) days. Platelet counts did not decrease to below 20 × 109/L in 4 patients requiring no platelet support at all; overall platelet counts >20 × 109/L were achieved within 0 to 35 (median 12) days. Fourteen patients experienced no GVHD at all; severe GVHD (grades 3 and 4) was the single major complication and the cause of death in 4 patients, occurring after early discontinuation of cyclosporine A. Relapse was reversed by allogeneic cell therapy in 2/3 cases, currently with no residual host DNA (male) by cytogenetic analysis and polymerase chain reaction. To date, with an observation period extending over 1 year (median 8 months), 22 of 26 patients (85%) treated by allogeneic nonmyeloablative stem cell transplantation are alive, and 21 (81%) are disease-free. The actuarial probability of disease-free survival at 14 months is 77.5% (95% confidence interval, 53% to 90%). Successful eradication of malignant and genetically abnormal host hematopoietic cells by allogeneic nonmyeloablative stem cell transplantation represents a potential new approach for safer treatment of a large variety of clinical syndromes with an indication for allogeneic BMT. Transient mixed chimerism which may protect the host from severe acute GVHD may be successfully reversed postallogeneic BMT with graded increments of donor lymphocyte infusions, thus resulting in eradication of malignant or genetically abnormal progenitor cells of host origin.

Nonmyeloablative Stem Cell Transplantation and Cell Therapy as an Alternative to Conventional Bone Marrow Transplantation With Lethal Cytoreduction for the Treatment of Malignant and Nonmalignant Hematologic Diseases

Myeloablative conditioning associated with hazardous immediate and late complications is considered as a mandatory first step in preparation for allogeneic blood or marrow transplantation (allogeneic BMT) for the treatment of malignant hematologic disorders and genetic diseases. Immune-mediated graft-versus-leukemia (GVL) effects constitute the major benefit of allogeneic BMT. Therefore, we have introduced the use of relatively nonmyeloablative conditioning before allogeneic BMT aiming for establishing host-versus-graft tolerance for engraftment of donor immunohematopoietic cells for induction of GVL effects to displace residual malignant or genetically abnormal host cells. Our preliminary data in 26 patients with standard indications for allogeneic BMT, including acute leukemia (n = 10); chronic leukemia (n = 8), non-Hodgkin's lymphoma (n = 2), myelodysplastic syndrome (n = 1), multiple myeloma (n = 1), and genetic diseases (n = 4) suggest that nonmyeloablative conditioning including fludarabine, anti-T-lymphocyte globulin, and low-dose busulfan (8 mg/kg) is extremely well tolerated, with no severe procedure-related toxicity. Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose of cyclosporin A as the sole anti-graft-versus-host disease (GVHD) prophylaxis resulted in stable partial (n = 9) or complete (n = 17) chimerism. In 9 patients absolute neutrophil count (ANC) did not decrease to below 0.1 x 10(9)/L whereas 2 patients never experienced ANC < 0.5 x 10(9)/L. ANC > or = 0.5 x 10(9)/L was accomplished within 10 to 32 (median, 15) days. Platelet counts did not decrease to below 20 x 10(9)/L in 4 patients requiring no platelet support at all; overall platelet counts > 20 x 10(9)/L were achieved within 0 to 35 (median 12) days. Fourteen patients experienced no GVHD at all; severe GVHD (grades 3 and 4) was the single major complication and the cause of death in 4 patients, occurring after early discontinuation of cyclosporine A. Relapse was reversed by allogeneic cell therapy in 2/3 cases, currently with no residual host DNA (male) by cytogenetic analysis and polymerase chain reaction. To date, with an observation period extending over 1 year (median 8 months), 22 of 26 patients (85%) treated by allogeneic nonmyeloablative stem cell transplantation are alive, and 21 (81%) are disease-free. The actuarial probability of disease-free survival at 14 months is 77.5% (95% confidence interval, 53% to 90%). Successful eradication of malignant and genetically abnormal host hematopoietic cells by allogeneic nonmyeloablative stem cell transplantation represents a potential new approach for safer treatment of a large variety of clinical syndromes with an indication for allogeneic BMT. Transient mixed chimerism which may protect the host from severe acute GVHD may be successfully reversed postallogeneic BMT with graded increments of donor lymphocyte infusions, thus resulting in eradication of malignant or genetically abnormal progenitor cells of host origin.

A retrospective study of ocular side effects in children undergoing bone marrow transplantation.

Bone marrow transplantation (BMT) is recognized as a successful treatment for malignant and non-malignant hematological diseases. Thanks to transplantation, the number of long-term survivors has risen and with the improved prognosis a problem of ocular side effects has arisen. We carried out a retrospective study to determine the incidence and etiopathogenesis of ocular complications in a series of young patients undergoing BMT. One hundred children (62 males and 38 females) with a mean age of 7.12 (+/- 3.3) years at the time of BMT (autologous in 66 cases, allogenic in 34) were followed for a mean of 4.2 years (range 2-9). The conditioning regimens preceding BMT induced cytoreductive chemotherapy alone (47 cases) or associated with total body irradiation (TBI) (53 cases) in three or six fractions for a total dose of 10-12 Gy. We examined every child before BMT and subsequently every six months. We did not include patients with ocular complications due to the primary disease. Thirty-three children showed several complications after BMT: 17 had subcapsular posterior cataract in both eyes and eight had tear hyposecretion; one had dramatic fungal panuveitis, four had hemorrhagic complications and five optic disk edema. TBI was significantly associated with the development of subcapsular posterior cataract.

A nonlethal conditioning approach to achieve durable multilineage mixed chimerism and tolerance across major, minor, and hematopoietic histocompatibility barriers.

Reconstitution of lethally irradiated mice with a mixture of syngeneic and allogeneic (A+B-->A) bone marrow results in multilineage mixed allogeneic chimerism, donor-specific transplantation tolerance, superior immunocompetence and resistance to graft-vs-host disease. However, the morbidity and mortality associated with lethal irradiation would be a major limitation to the clinical application of chimerism to induce tolerance for solid organ grafts or treat other nonmalignant hematologic diseases. We report here that durable multilineage mixed allogeneic chimerism and donor-specific transplantation tolerance for skin and primarily vascularized allografts can be achieved across multiple histocompatibility barriers using a nonmyeloablative radiation-based approach. The percentage of B10 mouse recipients that engrafted directly correlated with the degree of disparity between donor and recipient and the dose of total body irradiation administered. Although the occurrence of engraftment following conditioning with doses of total body irradiation of > or = 600 cGy was similar for animals receiving bone marrow disparate at MHC or MHC, minor and hematopoietic (Hh-1) loci (67% vs 78%), the level of donor chimerism was significantly less when multiple histocompatibility barriers were present (94.6 +/- 3.8% vs 37.5 +/- 12.5%). Treatment of the recipient with cyclophosphamide 2 days following allogeneic bone marrow transplantation reduced the dose of radiation sufficient for reliable engraftment to only 500 cGy of total body irradiation, regardless of MHC and Hh-1 disparity. Donor chimerism was stable and present in all lineages, with production of lymphoid (T and B cell), NK, and myeloid (erythrocyte, platelet, granulocyte, and macrophage) cells. Mixed chimeras exhibited donor-specific tolerance in vitro, as assessed by mixed lymphocyte culture (MLR) and cytotoxicity (CML) assays, and in vivo to skin and primarily vascularized cardiac allografts. The observation that engraftment and tolerance can be achieved across multiple histocompatibility barriers using nonmyeloablative recipient conditioning may allow allogeneic bone marrow transplantation to be applied to nonmalignant disease states in which lethal conditioning cannot be justified, including the induction of donor-specific tolerance for solid organ transplantation and the treatment of hemoglobinopathies and enzyme deficiency states.

First-line diagnosis based on immunological phenotyping in suspected acute leukemia: A prospective study

In a prospective analysis of the diagnostic value of immunophenotyping in acute leukemias (ALs), all patients admitted to a pediatric and a haematological department suspected of AL were examined consecutively with a selected panel of monoclonal antibodies (Mabs) against leucocyte differentiation antigens during an 8-month period. A total of 189 samples obtained from blood, bone marrow, spinal fluid and lymph nodes in 120 cases were all analysed blindly. The results were correlated with a routine morphological/cytochemical evaluation. Differing results were obtained in seven out of 38 cases in which the immunologically defined diagnosis was acute myeloid leukemia (AML), and in one out of 21 cases with the primary diagnosis acute lymphoid leukemia (ALL). Immunological phenotyping disclosed two cases of hybrid leukemia, one case of biphenotypic and one case of bilineal leukemia. No evidence of malignancy was found in 36 cases, 30 cases of blood and bone marrow and six cases of spinal fluids, in every case in accordance with the pathological examination. These results demonstrate that a first-line immunological evaluation of bone marrow, blood and spinal fluid from patients suspected of AL is highly capable of discriminating between different malignant and nonmalignant haematological diseases and also between various types of leukemias. The immunological methods do, however, require a sufficient amount of material which was a limiting factor in 14 out of 120 examinations, mainly from patients treated with several cycles of cytostatics. It is concluded that immunophenotyping can be used as a first-line diagnostic tool in malignant haematological diseases.

Intensive care therapy for patients with hematological diseases.

Treatment of patients with hematological diseases can be complicated by life-threatening problems such as shock, pneumonia, sepsis, or major bleeding. Some of these problems may result from direct effects of a malignant disease or from the cytopenias associated with some of the nonmalignant hematological diseases. But the side effects of bone marrow transplantation, radiation, chemotherapy, and surgery may also harm body defenses and vital organ system. The decision to admit a patient to an ICU should be guided by the patient’s prognosis. Patients with a hematological malignancy have very low survival rates once admission to an ICU becomes necessary [1–8]. This report concerns mortality and discharge rates of 84 admission of 77 patients with hematological diseases to the ICU of our hospital.

Bone marrow transplantation in patients with malignant and nonmalignant hematologic diseases

Bone marrow transplantation in patients with malignant and nonmalignant hematologic diseases