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G Bandini

Publications and source records attributed to G Bandini.

At least 55 records · Page 3Linked to original sources
PubMed1998

T cell alloreactivity induced by normal G-CSF-mobilized CD34+ blood cells.

In this study, the hypothesis that a subset of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ blood cells may actively induce an allogeneic T cell response in vitro was tested. Circulating CD34+ cells were purified to > or =98% by high gradient magnetic separation and then analyzed for the coexpression of HLA-DR, the common beta-chain of the leukointegrin family CD18 and costimulatory molecules CD80 (B7-1) and CD86 (B7-2). These antigens were expressed on average on: 94.9 +/- 2.5%, 64.4 +/- 15.4%, 0% and 1.9 +/- 1.2% CD34+ blood cells, respectively. Irradiated CD34+ cells induced a high proliferative response of allogeneic, but not autologous, purified CD4+ and CD8+ T cells in primary mixed leukocyte culture (MLC). An average three-fold lower CD4+ and CD8+ T cell response was induced by mononuclear cells from G-CSF-treated donors. A lower frequency of allostimulating cells among mononuclear cells rather than among CD34+ cells in the apheresis was documented by limiting dilution assay (LDA). As previously observed with marrow, sorted CD34+/CD18+ cells induced the proliferation of allogeneic T cells in MLC, while CD34+/CD18- cells, which were >94% HLA-DR+ and contained both committed (CFU-C) and early (LTC-IC) hematopoietic progenitors, stimulated allogeneic T cells poorly. Three-color staining cytofluorimetry indicated that expression of CD80 and CD86 were upregulated in 6.9 +/- 4.9 and 10.7 +/- 2.6% CD34+ blood cells respectively, after 24-30 h of culture with autologous or allogeneic mononuclear cells, or with CD4+, or CD8+ T cells, but not with medium alone. Moreover, the upregulation of CD86 was observed on CD34+/CD18+ rather than on CD34+/CD18- cells after 30 h in MLC. Blocking experiments demonstrated that preincubation of stimulator and responder cells with anti-CD80 plus anti-CD86 monoclonal antibodies induced a 84 +/- 8% inhibition of CD34+ cell allostimulating activity after 6 days in primary MLC. These results suggest that G-CSF-mobilized CD34+ hematopoietic progenitors with alloantigen presenting function express CD18 and may upregulate CD80 and CD86 upon interaction with T cells. Since activation of B7 costimulatory molecules represents an active costimulatory pathway on G-CSF-mobilized CD34+ cells, the blockade of these molecules or, alternatively, the use of selected non-immunogenic CD34+/CD18- blood stem cells may represent a new strategy for reducing graft rejection and overcoming HLA barriers in allogeneic stem cell transplantation.

Antibodies, Monoclonal↗
PubMed1998

High-dose busulfan and cyclophosphamide are an effective conditioning regimen for allogeneic bone marrow transplantation in chemosensitive multiple myeloma.

The present clinical trial was undertaken to investigate the toxicity and antimyeloma activity of busulfan (BU) and cyclophosphamide (CY) at the maximum tolerated doses of, respectively, 16 mg/kg and 200 mg/kg (BU-CY 4) as conditioning therapy for allogeneic bone marrow transplantation (BMT) in 19 consecutive patients with multiple myeloma (MM). Twelve (63%) had failed to respond to prior chemotherapy, while the remaining 37% had chemosensitive disease. No life-threatening or fatal regimen-related complications were observed. The incidence of veno-occlusive disease of the liver was zero according to Jones' criteria and 21% according to McDonald's system. Transplant-related mortality was 37%. Using stringent criteria, the frequency of complete remission (CR) was 42% among all patients and 53% among those who could be evaluated. With a median follow-up of 21 months for all patients and 66 months for survivors, the actuarial probability of survival and event-free survival at 4 years from BMT was 26% (95% CI: 7-46) and 21% (95% CI: 3-39), respectively. A more favorable outcome of transplantation was observed in the subgroup of patients with chemosensitive disease who had a transplant-related mortality of 14%, an overall CR rate of 86% (95% CI: 49-97) and a 4-year projected probability of event-free survival of 57% (95% CI: 20-93). Four of these patients are currently alive in continuous CR after 54, 66, 80 and 94 months, respectively. It is concluded that BU-CY 4 as conditioning for allogeneic transplantation for MM is associated with acceptable morbidity and relatively low mortality. This regimen exerts substantial antimyeloma activity, resulting in a high CR rate and durable responses, especially in patients with chemosensitive disease. Long-lasting remission and probable cure is possible following allogeneic stem cell transplantation for MM.

Adult↗
PubMed1998

Alloantigen presenting capacity, T cell alloreactivity and NK function of G-CSF-mobilized peripheral blood cells.

In this study we addressed whether the proportion and the function of antigen presenting cells (APC), T and NK lymphocytes are modified in the apheresis product of six healthy donors who received a stem cell mobilizing treatment with glycosylated G-CSF at 10 microg/kg/day x 5 days s.c. Flow cytometry analysis showed comparable percentages of HLA-DR+, CD19+, CD86+, CD80+ and CD1a+ cells in preG-CSF-peripheral blood mononuclear cells (preG-PBMC) and after mobilization in G-PBMC, whereas the proportion of CD14+ monocytes significantly increased in G-PBMC (3+/-1% vs 17+/-8%, P = 0.003). Analysis of lymphocyte subsets in preG-PBMC and G-PBMC showed similar proportions of CD3+, CD4+, CD8+ and CD28+ T cells, but a significantly lower percentage of CD16+ (11+/-7% vs 4+/-1%, P=0.01), CD56+ (15+/-6% vs 5+/-2%, P= 0.008), CD57+ (16+/-9% vs 5+/-2%, P=0.04), CD25+ (19+/-2% vs 9+/-6%, p=0.009) and CD122+ (5+/-2% vs 2+/-1%, P = 0.05) cells in G-PBMC. Unfractionated preG-PBMC and G-PBMC were irradiated and tested in primary mixed leukocyte culture (MLC) with two HLA-incompatible responders and induced efficient alloresponses in four of six cases, whereas G-PBMC stimulated poorly in the remaining two cases. Also, in allo-MLC with irradiated G-PBMC we detected lower amounts of IFN-gamma (P = 0.04) and of IL-2 (P = 0.06) than in allo-MLC with preG-PBMC. Furthermore, freshly isolated preG-PBMC and G-PBMC from each donor exerted comparable allogeneic responses to HLA-incompatible irradiated mononuclear cells in all cases. However, G-PBMC showed no NK activity against K562 target cells at any effector:target ratio tested. These data suggest that normal G-PBMC may prevent Thl alloresponses, maintain efficient alloreactivity to HLA mismatched antigens and have impaired NK activity.

Antigen Presentation↗
PubMed1998

Allogeneic peripheral blood stem cell transplantation in patients with early-phase hematologic malignancy: a retrospective comparison of short-term outcome with bone marrow transplantation.

BACKGROUND AND OBJECTIVE: Transplantation of mobilized allogeneic peripheral blood stem cells (PBSC) has recently been reported by several groups. However, few patients receiving an allograft in the early stage of their disease have been described so far. DESIGN AND METHODS: Fifteen patients with early stage hematologic malignancies were transplanted with cryopreserved allogeneic PBSC from HLA-identical siblings. PBSC were collected after priming with 10 micrograms/kg/day of glycosylated granulocyte colony-stimulating factor (G-CSF, lenograstim). Outcomes were compared to a historical control group of 15 patients who received conventional bone marrow transplantation (BMT) from HLA-identical sibling donors. The two groups were matched for diagnosis, stage of disease, age, preparative regimen, graft-versus host (GVHD) prophylaxis, patients' and donors' gender and cytomegalovirus (CMV) serology. Diagnoses in both groups were: chronic myelogenous leukemia (CML) in first chronic phase (= 5), acute leukemia in first complete remission (CR) (= 5), non-Hodgkin's lymphoma in CR (= 1) and multiple myeloma (MM) with sensitive disease (= 4). All patients were given cyclosporin-A (CsA) and methotrexate (MTX) for GVHD prophylaxis. Preparative regimens varied according to diagnosis and included either busulfan/cyclophosphamide combination (BU/Cy) or total body irradiation/cyclophosphamide +/- melphalan (TBI/Cy +/- Mel). RESULTS: The patients in the PBSC group showed a more rapid hematopoietic reconstitution with a significant difference in the median times to 1 x 10(9) neutrophils/L (19 days vs. 26 days; p = 0.03) and to platelet transfusion independence (18 days versus 22 days; p = 0.02). This finding was associated with a significantly shorter hospitalization (28 days versus 33 days after transplantation; p = 0.01). In the PBSC series, grade II-IV acute GVHD occurred in 3 patients (20%) and grade III-IV in 1 patient (7%). In the BMT control group, grade II-IV aGVHD was reported in 2 cases (13%; p = NS) and 1 case had grade III-IV GVHD. Chronic GVHD developed in 7 patients (47%) (limited = 6; extensive = 1) undergoing PBSC transplantation and 5 patients (33%) (limited = 4; extensive = 1) in the BMT series (p = NS). No difference was found in the incidence of grade II-IV (according to the World Health Organization) mucositis, whereas PBSC recipients did have a significantly lower incidence of additional severe (grade III-IV) organ toxicity. After a median follow-up of 300 days (range 180-630), all PBSC patients are still alive with a median Karnofsky score of 100% (range 80%-100%). Thirteen patients are in CR and 2 myeloma patient are in good partial remission (PR). Also, in the BMT group the peritransplant mortality was absent; two MM patients died due to progressive disease at day +796 and +1,023, respectively; one leukemic patient died of chronic GVHD 407 days after transplantation and one additional leukemic individual relapsed 1,140 days after BMT. INTERPRETATION AND CONCLUSIONS: This retrospective comparison suggests that allogeneic PBSC transplantation performed in the early stage of the disease is safe and may be associated with a more rapid hematopoietic reconstitution than BMT, as well as lower transplant-related toxicity and earlier hospital discharge with apparently no increased risk of acute and chronic GVHD.

Adolescent↗
PubMed1998

Clinical use of allogeneic hematopoietic stem cells from sources other than bone marrow.

BACKGROUND AND OBJECTIVE: Peripheral blood stem cells (PBSC) are being increasingly used as an alternative to conventional allogeneic bone marrow (BM) transplantation. This has prompted the Working Group on CD34-Positive Hematopoietic Cells to evaluate the current utilization of allogeneic PBSC in clinical hematology. EVIDENCE AND INFORMATION SOURCES: The method employed for preparing this review was that of informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to reach an agreement on different opinions and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of stem cell transplantation and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: Review of the current literature shows that unmanipulated allogeneic PBSC give prompt and stable engraftment in HLA-identical sibling recipients. Despite the much higher number of T-cells infused, the incidence and severity of acute GVHD after PBSC transplant seems comparable to that observed with bone marrow (BM) cells. In comparison to the latter, PBSC probably ensure faster immunologic reconstitution in the early post-transplant period. Controversial results on the incidence and severity of acute-GVHD have been reported when CD34+ selection methods are used. Prospective randomized trials are underway to compare the results of PBSC and BM allogeneic transplantation. In mismatched family donor transplants, T-cell depleted PBSC successfully engraft immune-myeloablated recipients through a megacell-dose effect able to overcome the HLA barrier. Experience with PBSC in the context of unrelated donor transplants is currently anecdotal and prospective trials should be completed before that practice becomes routine. Finally, there is also limited evidence that, following induction chemotherapy, the addition of PBSC to donor lymphocyte infusion (DLI) for treatment of leukemia relapse after BMT may improve the safety and effectiveness of DLI itself. Concerning cord blood (CB) transplants, the most interesting aspects are the ease of CB collection and storage, the low risk of viral contamination and the low immune reactivity of CB cells. This last property has its clinical counterpart in an apparently reduced incidence and severity of acute GVHD both in sibling and unrelated CB transplants, probably making the level of donor/recipient HLA disparity acceptable a greater degree with respect to what is required for transplants from other sources.

Blood Cells↗
PubMed1998

Prior treatment with alpha-interferon does not adversely affect the outcome of allogeneic BMT in chronic phase chronic myeloid leukemia.

BACKGROUND AND OBJECTIVE: Controlled clinical trials have shown that Interferon-alpha (IFN-alpha) is able to control myeloid proliferation and to suppress the Ph+ clonal hemopoiesis in early chronic phase chronic myeloid leukemia (CML): a growing number of patients are treated with this agent from diagnosis. However, if a CML patient has an HLA-identical sibling, bone marrow transplant (BMT) represents the best choice of treatment. Since IFN-alpha is known to modify the immunologic response and to increase marrow fibrosis, information is needed on the outcome of patients transplanted after IFN-alpha treatment. DESIGN AND METHODS: We analyzed retrospectively 32 Ph+ CML patients submitted to BMT in the last 6 years in Institute "Serágnoli". All the patients were in 1st chronic phase, their median age was 37 years, the donors were HLA-identical (27/32) or 1 Ag-mismatched (5/32) siblings. Big BuCy was the conditioning regimen employed for all and GVHD prophylaxis was based on CsA in 4 patients and Csa+MTX in 28 patients; all patients received homogeneous pre and post-transplant supportive care, antimicrobial and antiviral prophylaxis. These patients were divided into 2 groups according to the treatment before BMT: 16 received IFN from diagnosis to BMT (mean dose 6.9 MU/daily) for at least 6 mos (mean 23 mos, range 8-75) and 16 received chemotherapy alone (hydroxyurea [HU]). RESULTS: Hematological recovery was comparable in the two groups: time to 0.5 x 10(9)/L PMN was 20.5 days (range 11-32) in the IFN group and 20 days (range 10-32) in the HU group; time to 50 x 10(9)/L platelets was 28 days (range 20-117) in the IFN group and 27 days (range 20-112) in the HU group. The incidence of acute GVHD was not different in the two groups for any grade of the disease; in patients who survived more than 100 days, chronic GVHD occurred in the two groups with the same frequency. Seven patients died of transplant related mortality (TRM), 4 in the IFN group and 3 in the HU group. Hematological relapse was observed in only one case in the HU group; no cytogenetic relapse occurred. Disease free survivals at 7 years are 61% and 72%, respectively; the difference is not significant. INTERPRETATIONS AND CONCLUSIONS: Notwithstanding the low number of patients included in this study, the data reported here confirm that prior treatment with alpha-IFN does not adversely affect transplant outcome.

Adult↗
PubMed1997

Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.

Adolescent↗
PubMed1996

HLA-identical sibling bone marrow transplantation in younger patients with chronic lymphocytic leukemia. European Group for Blood and Marrow Transplantation and the International Bone Marrow Transplant Registry.

OBJECTIVE: To characterize in detail the outcomes of HLA-identical sibling bone marrow transplantation for chronic lymphocytic leukemia (CLL) in patients younger than 60 years of age. DESIGN: Retrospective cohort study. SETTING: 30 centers for bone marrow transplantation worldwide, which reported data on outcome of HLA-identical sibling bone marrow transplantation for CLL to the European Group for Blood and Marrow Transplantation or the International Bone Marrow Transplant Registry between 1984 and 1992. PATIENTS: 54 patients diagnosed with CLL (median age, 41 years; range, 21 to 58 years). The median interval from diagnosis to transplantation was 37 months (range, 5 to 130 months). At the time of transplantation, 3 patients were at Rai stage 0; 10 were at stage 1; 10 were at stage 2; 7 were at stage 3; and 22 were at stage 4. INTERVENTION: Transplant regimens varied. Most patients received high-dose cyclophosphamide and total body irradiation, followed by infusion of bone marrow from an HLA-identical sibling. After transplantation, immune suppression with cyclosporine or methotrexate or both was generally used to prevent graft-versus-host disease. MEASUREMENTS: The primary outcome was survival. We also studied hematologic remission, defined as normalization of the leukocyte count, hemoglobin level, and platelet count, and absence of lymphadenopathy and splenomegaly. RESULTS: 38 patients (70%) achieved hematologic remission. Twenty-four (44%) remain alive a median of 27 months (range, 5 to 80 months) after transplantation. Three-year survival probability was 46% (95% CI, 32% to 60%). Three patients who received transplants at Rai stage 0 remain alive 21, 32, and 45 months after transplantation. Three-year survival probabilities were as follows: 68% (CI, 38% to 98%) in 10 patients who received transplants at Rai stage 1, 30% (CI, 2% to 58%) in 10 patients who received transplants at Rai stage 2, 57% (CI, 21% to 93%) in 7 patients who received transplants at Rai stage 3, and 34% (CI, 12% to 56%) in 22 patients who received transplants at Rai stage 4 CLL. Five patients (9%) died of progressive leukemia and 25 (46%) of treatment-related complications. CONCLUSIONS: Bone marrow transplants from HLA-identical siblings can result in hematologic remission and survival in persons with CLL, but it is uncertain how these results compare with those of conventional therapies.

Adult↗
PubMed1996

Fingerprinting of HLA class I genes for improved selection of unrelated bone marrow donors.

The degree of matching of HLA genes between the selected donor and recipient is an important aspect of the selection of unrelated donors for allogeneic bone marrow transplantation (UBMT). The most sensitive methods currently used are serological typing of HLA class I genes, mixed lymphocyte culture (MLC), IEF and molecular genotyping of HLA class II genes by direct sequencing of PCR products. Serological typing of class I antigenes (A, B and C) fails to detect minor differences demonstrated by direct sequencing of DNA polymorphic regions. Molecular genotyping of HLA class I genes by DNA analysis is costly and work-intensive. To improve compatibility between donor and recipient, we have set up a new rapid and non-radioisotopic application of the 'fingerprinting PCR' technique for the analysis of the polymorphic second exon of the HLA class I A, B and C genes. This technique is based on the formation of specific patterns (PCR fingerprints) of homoduplexes and heteroduplexes between heterologous amplified DNA sequences. After an electrophoretic run on non-denaturing polyacrylamide gel, different HLA class I types give allele-specific banding patterns. HLA class I matching is performed, after the gel has been soaked in ethidium bromide or silver-stained, by visual comparison of patients' fingerprints with those of donors. Identity can be confirmed by mixing donor and recipient DNAs in an amplification cross-match. To assess the technique, 10 normal samples, 22 related allogeneic bone marrow transplanted pairs and 10 unrelated HLA-A and HLA-B serologically matched patient-donor pairs were analysed for HLA class I polymorphic regions. In all the related pairs and in 1/10 unrelated pairs, matched donor-recipient patterns were identified. This new application of PCR fingerprinting may confirm the HLA class I serological selection of unrelated marrow donors.

Base Sequence↗
PubMed1996

Endothelium and bone marrow transplantation.

Thrombotic complications may occur early after marrow transplantation and many data suggest that endothelial injury plays a pivotal role in their pathogenesis. Since plasma thrombomodulin and P-selectin are thought to be of value as markers of vascular endothelial cell membrane injury, we investigated their plasma concentration in bone marrow transplant patients aiming better to clarify the degree of endothelial involvement. Plasma thrombomodulin and P-selectin were monitored in 25 patients without thrombotic complications before transplant, on day 0 and weekly for 1 month thereafter, while in three patients who developed VOD monitoring continued until day +52. These proteins were in the normal range in all the uncomplicated patients and in two with reversible VOD, while they were always very high in the only patient who developed very severe and lethal VOD. In conclusion, we suggest that endothelial activation/damage occurs rarely in the course of BMT for hematological malignancies; we were able to document endothelial injury in only one patient with very severe thrombotic complication.

Adolescent↗
PubMed1996

Autologous bone marrow transplantation in late first complete remission improves outcome in acute myelogenous leukemia.

We evaluated the role of ABMT in late 1st CR AML adult patients using busulfan plus cyclophosphamide as preparative regimen. Fifty-one adult patients (mean age 36 years, range 15-59) with AML underwent ABMT in 1st CR. Three of them had a prior diagnosis of myelodysplastic syndrome; one patient had a secondary leukemia. The median interval between CR and ABMT was 8 months (range 4-20). Patients received busulfan, 4 mg/kg/day for 4 days plus cyclophosphamide 50 mg/kg/day for 4 days or 60 mg/kg/day for 2 days. No maintenance chemotherapy was administered after ABMT. Median days to reach 0.5 x 10(9)/I PMN and 20 x 10(9)/I platelets were 26 (range 12-250) and 74 (range 16-740), respectively. No transplant-related deaths were observed. Five-year actuarial overall survival rate is 76.9%; actuarial leukemia-free survival rate is 70.6%. Mean follow-up from ABMT is 35 months. Leukemia-free survival of this group was compared with that of 38 non-transplanted patients younger than 60 years, who maintained a CR longer than 8 months in the same period. This analysis shows a statistically significant difference in favor of ABMT patients. These results suggest that, even if performed late after 1st CR as post-remission intensification, ABMT can improve the outcome of AML patients.

Adolescent↗
PubMed1995

Allogeneic bone marrow transplantation from HBsAg+ donors: a multicenter study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

Hepatitis B virus (HBV)-infected individuals are occasionally used as donors for bone marrow transplantation (BMT). We studied the rate of HBV infection and the clinical expression of the associated liver disease in patients receiving marrow from HBsAg+ donors. We performed a retrospective survey in 14 BMT units in Italy in which all BMTs performed between 1984 and 1994 were reviewed and those involving HBsAg+ donors were identified. Donors and recipients were analyzed for HBV markers and liver disease. A total of 24 of 2,586 patients (0.9%) had received an HBsAg+ marrow. HBsAg became detectable in 22% of pre-BMT HBsAg- patients, but only 5.5% became chronic HBsAg carriers. Antigenemia developed more frequently in anti-HBs- compared with anti-HBs+ patients independently of passive prophylaxis with hyperimmune anti-HBs Ig, although the difference was not significant. Severe liver failure with death occurred in 21% of patients, which was a value greater than that generally observed after BMT in our units (3.7%). Patients with an anti-HBe+ donor had higher frequency of liver failure (28% v 0%) and alanine aminotransferase peaks as compared with those of patients with an HBeAg+ donor. Liver failure was not observed in anti-HBs+ recipients. The use of HBsAg+ donors, particularly if anti-HBe+, increases the risk of severe liver disease in BMT recipients. Anti-HBs positivity may prevent severe liver damage.

Adolescent↗
PubMed1995

Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation.

Acute graft-versus-host disease (aGVHD) has been classified according to the Seattle criteria as grades 0, I, II, III, and IV for 20 years. The predictive value of such detailed grading is a matter of debate; publications usually report GVHD as present or absent or as absent, moderate, or severe. The Working Party Chronic Leukemia of the European Group for Bone Marrow Transplantation analyzed data of 1,294 patients transplanted from an allogeneic donor for chronic myelogenous leukemia (CML) in first chronic phase and tested the predictive value of aGVHD grading for the following end-points: day 100 mortality (D100M), transplant-related mortality (TRM), relapse incidence (RI), leukemia-free survival (LFS), and survival (SURV). aGVHD was absent in 462 patients (35.7%), grade I occurred in 335 (25.8%), grade II in 264 (20.5%), grade III in 110 (8.5%), and grade IV in 123 patients (9.5%). A total of 297 patients (23%) died within 100 days, 495 patients (38%) died of any TRM, and 100 patients (8%) died of relapse. D100M according to grades 0, I, II, III, and IV was 17%, 13%, 19%, 38%, and 70%, respectively, with significant difference between 0-II versus III-IV. TRM was 28%, 27%, 43%, 68%, and 92%, respectively, with a distinct separation between 0-I versus II-IV. RI showed a continuous decrease of 37%, 30%, 23%, 18%, and 8%, respectively, with increasing aGVHD. LFS was 45%, 51%, 44%, 26%, and 7%, respectively, and was best for patients with grade I aGVHD. This finding was also reflected in a better overall survival (60%, 64%, 53%, 30%, and 8%, respectively). The better LFS for grade I aGVHD patients compared with patients with grade 0 or II aGVHD was confirmed (P = .05) in a multivariate analysis. These data document the value of the present 5-point grading of aGVHD, ie, different outcome is observed depending on endpoint analyzed. Restricting information about aGVHD to presence or absence is not warranted.

Acute Disease↗
PubMed1995

Molecular analysis of PML-RAR alpha fusion mRNA detected by reverse transcription-polymerase chain reaction assay in long-term disease-free acute promyelocytic leukaemia patients.

By use of RT-PCR of PML/RAR alpha, we evaluated bone marrow aspirates in 10 patients with APL in long-term disease-free status after induction chemotherapy and consolidation (median 54 months: range 33-101 months from complete remission). All patients were in clinical and cytogenetic remission at the time of molecular evaluation (range 32-96 months from CR). All patients but one were found to be RT-PCR negative at the molecular level for the expression of PML-RAR alpha transcript, confirming that the majority of the patients with long-term survival of APL are characterized by the eradication of the neoplastic clone.

Bone Marrow↗
PubMed1995

Molecular analysis of HLA genes for the selection of unrelated bone marrow donor.

The selection of fully matched unrelated volunteer donors (UVD) in BMT requires a molecular characterization of MHC polymorphism, since most phenotypically HLA-identical donors can be non-identical when analyzed at a genomic level. The present report describes a molecular typing protocol for HLA genes developed for the selection of UVD, and its application to some donor-recipient pairs. The protocol involves three successive steps. Firstly, PCR with sequence-specific primers for HLA-DRB1 and -DQB1 genes is performed to identify the major alleles of the recipient. PCR-fingerprint matching is then introduced for HLA-A, B, C and DRB, DQB and DPB genes to screen prospective donors. Those showing matched fingerprinting patterns are finally submitted to direct sequencing of the DRB1 gene. DPB compatibility is assessed by oligotyping when there are several potential class I and DRB matched donors. This strategy was applied retrospectively to three BMT recipients and their previously selected donors. Three other patients and their 12 prospective donors were submitted to our protocol before BMT. Clinical evaluation of transplant outcomes indicates the primary importance of complete DRB and class I matching, while DQB and DPB compatibility seems to be less critical.

Base Sequence↗
PubMed1994

Autoimmune neutropenia after unrelated bone marrow transplantation.

A 26-year-old male with Ph+ chronic myeloid leukemia, recipient of an HLA-compatible marrow from a matched unrelated donor, showed good platelet engraftment coupled with poor neutrophil recovery. On day +33 the presence of surface-bound anti-neutrophil antibodies was detected by immunofluorescence. At variance with previously reported cases, the WBC count improved without any specific treatment, and the test became negative on day +42.

Adult↗