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D Rondelli

Publications and source records attributed to D Rondelli.

At least 55 records · Page 3Linked to original sources

Alloantigen presenting function of normal human CD34+ hematopoietic cells.

The identification of the CD34 molecule, expressed almost exclusively on human hematopoietic stem cells and committed progenitors, and the development of CD34-specific monoclonal antibodies have made procurement of relatively pure populations of CD34+ marrow cells for autologous transplantation feasible. Characterization of the immunogenicity of CD34+ marrow cells may facilitate the design of successful strategies to use these cells for allogeneic transplantation. CD34+ marrow cells from normal volunteers were enriched to greater than 98% purity by immunoaffinity chromatography on column followed by fluorescence-activated cell sorting. Purified CD34+ cells were tested for expression of HLA-DR and other accessory molecules, and function in hematopoietic colony growth and mixed leukocyte culture (MLC) assays. Greater than 95% CD34+ cells were positive for HLA-DR and 74% +/- 10% were highly positive for CD18, the common beta-chain of a leukointegrin family. CD34+/CD18- cells were small, agranular lymphocytes which contained the majority of precursors for colony-forming cells detected in long-term cultures. They produced almost no stimulation of purified T cells from HLA-DR-incompatible individuals in bulk MLC or in limiting dilution assay. In contrast, CD34+/CD18+ cells were large, were enriched for cells forming mixed colonies in short- but not long-term assays, and were capable of stimulating allogeneic T cells. CD86, a natural ligand for the T-cell activation molecule CD28, was coexpressed with CD18 in 6% +/- 3% of CD34+ cells. CD34+/CD86+ cells, but not CD34+/CD86- cells, exhibited strong alloantigen presenting function. Thus, pluripotent hematopoietic activity and alloantigen presenting function are attributes of distinct subsets of CD34+ marrow cells. CD34+/CD18- or CD34+/CD86- cells may be more effective than either the whole CD34+ population or unseparated marrow in engrafting allogeneic recipients and may also facilitate induction of tolerance.

Adult↗

Immunologic and clinical modifications following low-dose subcutaneous administration of rIL-2 in non-Hodgkin's lymphoma patients after autologous bone marrow transplantation.

In order to induce a therapeutic immunomodulatory activity, 11 patients with high-grade non-Hodgkin's lymphoma (HG-NHL) at a median of 42 days after autologous bone marrow transplantation (ABMT) received recombinant interleukin-2 (rIL-2) subcutaneously at a dose of 2 international megaunits (IMU)/m2 every other day for 2 weeks and then 3 IMU/m2 twice a week for 1 year. Immunological studies, including T and natural killer (NK) cell subset assessment, together with functional assay, such as NK and CD16-mediated cytotoxic activities, were performed before therapy, after 2 weeks and then monthly. Phenotypic analyses showed a significant and persistant (P = 0.001) increase in the proportion and absolute number of total lymphocytes and, particularly of both CD16 and CD56 NK cells, from pre-treatment values of 14 and 18% to 30 and 38% respectively, recorded after 6 months of therapy. No changes were observed in CD25 (p55)-positive cells, while a significant increase from 13 to 33% (after 6 months) was observed in CD122-positive cells. Furthermore, rIL-2 administration led to an enhancement of NK activity even at the lowest effector:target ratio and of CD16-mediated cytotoxic activity. Clinical tolerance was acceptable with moderate fever and fluid retention observed only at the onset of rIL-2 treatment. None of the patients have progressed with a median follow-up of 22 months (range 10-42 months) after starting therapy. In addition, two patients with a residual disease after ABMT, one in the liver and the second in the lymph nodes, obtained a complete response after 10 and 7 months of rIL-2 therapy, respectively. These preliminary data suggest that the infusion of low-dose rIL-2 s.c. after ABMT is safe and well tolerated and can selectively increase the NK cell number and function. Additional patients are needed in order to assess the impact of these immunological changes on relapse-free survival after ABMT for HG-NHL.

Adjuvants, Immunologic↗

The presence of lymphoid-associated antigens in adult acute myeloid leukemia is devoid of prognostic relevance.

The immunophenotype of 110 adult patients with diagnosis of acute myeloblastic leukemia (AML) was analyzed using a wide panel of monoclonal antibodies (mAbs). Leukemic blasts were tested by applying direct immunofluorescence analysis and dual-fluorescence staining, and two groups of patients were identified: 56/110 (51%) expressing only myeloid antigens (My/AML) and 54/110 (49%) expressing both myeloid and lymphoid antigens (Ly/AML). CD13 and CD33 were expressed in almost all FAB subtypes, whereas CD14, frequently expressed in M4 and M5 subtypes (70%), was rarely expressed in M0 + M1 cases (9%). On the contrary, CD34, expressed in 77% of M0 + M1 cases, was practically absent in M3 and M5 subtypes (6% and 7%, respectively). CD2 and CD7 antigens were found in 34% and 42% of patients respectively, whereas B cell-associated antigens, such as CD10 and CD19, were found in 31% and 18% of patients. Cytogenetic abnormalities characteristically present in AML patients were also analyzed and, except for t(8;21) which was found in both groups of patients, the other abnormalities were frequently found in cases coexpressing lymphoid-associated antigens. Finally, the complete remission (CR) rate, survival and event-free survival were analyzed according to the presence of lymphoid markers and also of some specific antigens such as CD7 and CD34. The only prognostic difference was represented by CD34+ patients who showed a reduction in the CR rate compared with CD34- patients (65% versus 82%) (p = 0.05) which became more evident when the mean intensity of fluorescence was considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Low doses of rIL2 after autologous bone marrow transplantation induce a "prolonged" immunostimulation of NK compartment in high-grade non-Hodgkin's lymphomas.

Ten patients with high-grade non-Hodgkin's lymphoma (HG-NHL) entered a subcutaneous (s.c.) recombinant interleukin 2 (rIL2) trial within 2 months of undergoing autologous bone marrow transplantation (ABMT). Immunological studies, consisting in T- and natural killer (NK)-cell subset assessment, together with functional assays, such as NK activity and CD16-mediated redirected killing assay, were performed before therapy, after 2 weeks, and then monthly. Phenotypic analysis showed a significant increase (p = 0.01) of CD16 and CD56 NK cells, from 12% to 28% and from 17% to 37%, respectively. In particular, the CD56bright NK cell population showed a tenfold increase, while CD56dim NK cells remained unmodified compared with pretreatment values. The expression of IL2 receptors was also studied and a significant increase (p = 0.01) of CD122 (p75)-positive cells from 8% to 30% was found, while no significant increase was observed in CD25 (p55)-positive cells. Furthermore, rIL2 administration led to an increase of NK activity even at the lowest effectors:target ratio and to an increase of CD16-mediated redirected killing assay. These phenotypic and functional modifications lasted throughout the duration of rIL2 therapy and remained after completion of therapy. In addition, none of the ten patients relapsed, and two of them who started IL2 treatment while still showing residual disease experienced a complete disappearance of the disease after 10 and 7 months of therapy, respectively. Our data suggest that infusion of rIL2 s.c. after ABMT is safe, can selectively increase NK cell number and function, and may have a beneficial effect on the minimal residual disease.

Adult↗

Cytofluorimetric and functional analysis of c-kit receptor in acute leukemia.

The SR-1 monoclonal antibody (MoAb) recognizes an epitope of the c-kit receptor (KR), present on normal hemopoietic CD34+ stem cells as well as on blasts from patients with acute leukemia. Cytometric analysis by indirect immunofluorescence with the SR-1 MoAb was performed in 98 patients with acute myeloblastic leukemia (AML) and in 37 patients with acute lymphoblastic leukemia (ALL) in order to detect the presence of the KR and to examine its prognostic significance. Sixty-nine of 98 (70%) AML patients were SR-1 positive independently of the FAB subtype, although a higher incidence of SR-1 positive cases was observed in M4 and M5 AML and in those cases that also coexpressed lymphoid antigens. Fourteen AML samples were studied by Northern blot analysis and the KR mRNA was detected in the majority of SR-1 positive cases and also in 2 of 3 SR-1 negative samples. Furthermore, "in vitro" cultures from 15 cases showed that recombinant human Stem cell factor (rhSCF) induced an increased proliferative activity in most tested cases (11/15); this was further enhanced when rhSCF was combined with rhIL-3 + rhGM-CSF (p = 0.007) and with the GM-CSF/IL-3 fusion protein PIXY321 (p = 0.003). Thirty-seven ALL cases were also studied and all but one were SR-1 negative. Interestingly, the only SR-1 positive case also coexpressed myeloid antigens and showed an "in vitro" response when stimulated with rhSCF. Finally, the complete remission (CR) rate, survival and event-free survival were evaluated in 75 AML patients who received standard and identical chemotherapy; unlike previous studies which utilized a different anti-KR MoAb (YB5.B8) and which showed a poor prognosis for KR positive patients, we were unable to document any significant difference in CR rate, survival and event-free survival.

Adolescent↗

Increased expression of myeloid antigen markers in adult acute lymphoblastic leukaemia patients: diagnostic and prognostic implications.

By applying direct immunofluorescence with a dual-staining technique we were able to demonstrate that 20/37 (54%) patients with acute lymphoblastic leukemia (ALL) expressed both lymphoid and myeloid antigens on the same leukaemic cells. CD13 and CD33 myeloid antigens were detected in 18/20 and in 15/20 cases respectively, and both in 13. Molecular studies confirmed that the four patients with T-cell phenotype had molecular rearrangement of T-cell receptor (TcR) beta chain, and 26 ALL patients with 'B-cell' phenotype showed JH rearrangement. Two ALL patients without (ALL/My-) and three with myeloid antigens (ALL/My+) also demonstrated bcr/abl rearrangement. Both groups of patients had similar presenting features such as age, sex, Hb level, white blood cells, platelet counts and cytogenetic features. Complete response was achieved in 16/17 (94%) ALL/My- patients and in 15/18 (83%) ALL/My+ patients (two deaths occurred during induction) with a mean duration of 17 and 16 months respectively and with similar survival and event-free survival curves. Myeloid antigen expression in adult ALL patients may occur more frequently than previously reported. The presence of myeloid antigen does not identify, in our series, a higher-risk subgroup of patients, although lack of any statistical evidence of prognostic significance needs to be confirmed in a larger case study.

Adolescent↗

Rapid restoration of natural killer activity following treatment with 2-chlorodeoxyadenosine in 22 patients with hairy-cell leukemia.

We report on the T-cell profile and natural killer (NK) function in 22 hairy cell leukemia patients before and 2 and 6 months after a single 7-day course of 2-CdA therapy at a dose of 0.1 mg/kg daily continuous infusion. Before treatment, two groups of patients were identified in respect to NK activity: the first (12/22) had a normal number of T and NK cells and a normal NK activity, the second (10/22) showed a severe reduction of CD3+, CD4+, CD16+, and CD56+ cells, together with impaired NK activity. All patients had increased serum levels of the soluble interleukin 2 receptor (sIL-2R). Along with a high complete remission rate (77%), treatment with 2-CdA produced a significant reduction (p = 0.001) of total lymphocytes (from 1.59 x 10(9)/l to 0.72 x 10(9)/l), and particularly of CD4+ cells (from 0.68 x 10(9)/l to 0.23 x 10(9)/l), while CD8+, CD16+ and CD56+ cells were less affected. Despite the dramatic reduction of lymphocytes which lasted for more than 6 months, 7/10 patients with impaired NK function before starting 2-CdA therapy normalized the cytotoxic function within 2 months. In conclusion, 2-CdA produces a severe reduction of lymphocytes in general, and of CD4 lymphocytes in particular, whilst it may produce a significant increase in the proportion of NK cells leading, together with a normalization of the sIL-2R serum levels, to a rapid restoration of the NK cytotoxic function in the majority of patients.

Adult↗

Molecular evaluation of clonal remission in hairy cell leukemia patients treated with 2-chlorodeoxyadenosine.

Several reports have documented complete and long-lasting remissions in hairy cell leukemia (HCL) patients after a single one-week course of 0.1 mg/kg/d of 2-Chlorodeoxyadenosine (2-CdA) administered by intravenous infusion. In these studies the evaluation of the clinical response was based on physical examination, blood cell counts, as well as cytochemical and immunological detection of residual leukemic cells. Since HCL is a chronic lymphoproliferative disorder characterized by the expansion of monoclonal B cells, analysis of the configuration of the immunoglobulin gene regions represents a valuable tool towards a more accurate monitoring of treatment response. We hereby describe the molecular assessment of the neoplastic clone in six HCL patients treated with 2-CdA; in five of them a disappearance of the rearranged bands could be documented in bone marrow cells aspirated between 2 and 21 months after a single course of continuous infusion 2-CdA. The last HCL case analyzed, revealed molecular persistence of the neoplastic clone. In all cases but one, the molecular evaluation was in agreement with the definition of clinical response based on conventional analysis. This study demonstrates that HCL patients treated with 2-CdA show a high incidence of molecularly-defined complete remissions, the likelihood of which is much greater than for patients treated with Interferon alpha.

Bone Marrow↗

Retreatment with 2-CdA of progressed HCL patients.

Thirty seven hairy cell leukemia (HCL) patients, 35 males and 2 females with a median age of 53 years, were treated with a single course of 2-Chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily for 7 days by continuous infusion. Twenty nine (78%) achieved a complete remission (CR) and 8 (22%) a partial remission (PR); four of the latter progressed after 6, 12, 18 and 24 months. All have been retreated with 2-CdA and 2 achieved a CR, 1 a PR and the last one is not yet evaluable. The overall median duration of response was 18 months, ranging from 4 to 30 months from the end of therapy. Circulating hairy cells and spleen enlargement, when present, disappeared within 2 weeks after completing treatment. A significant neutropenia was observed in almost all patients mainly in those who had less than 1,000/microliters neutrophils when treatment was started, together with a significant lymphocytopenia which lasted for more than 12 months. The hemoglobin and platelet levels were marginally affected. Fever was observed in 14 patients; in 8 of them it was short-lived (< or = 48 hours) and apparently not infection-related, while in the remaining 6 it was attributed to infection. Clinical tolerance was very good and none of the patients complained of nausea, vomiting or hair loss. In conclusion, our study confirms the efficacy of 2-CdA in HCL, including patients who progressed after treatment with 2-CdA.

Adult↗

Bone-marrow biopsy in hairy cell leukaemia (HCL) patients. Histological and immunohistological analysis of 46 cases treated with different therapies.

Serial bone-marrow biopsies were obtained from 46 hairy cell leukaemia (HCL) patients at different time intervals during the course of their disease. The patients were treated according to the following schemes: 14 received alpha-lymphoblastoid interferon (alpha-IFN), 11 2-Chlorodeoxyadenosine (2CdA), and 21 alpha-IFN first, followed by 2CdA. All the biopsies were studied by immunohistochemical means for the detection of minimal residual disease. The administration of 2CdA produced the highest reduction of both the tumor burden and HC index, with residual hairy cells (HCs) being undetectable at conventional light microscopy in most cases. In addition, 2CdA induced a higher degree of hypocellularity than alpha-IFN: the reduction in the amount of normal bone-marrow, however, was less pronounced in patients who had alpha-IFN before 2CdA. Of 9 patients who received both alpha-IFN and 2CdA and were followed for more than 2 years, 3 relapsed, while the remaining 6 continued to show rare HCs 2 years after 2CdA administration.

Adult↗

In vitro susceptibility of acute leukemia cells to the cytotoxic activity of allogeneic and autologous lymphokine activated killer (LAK) effectors: correlation with the rate and duration of complete remission and with survival.

Acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) blasts were studied for their sensitivity to the lytic activity of normal allogeneic interleukin 2 (IL-2) activated killer (LAK) cells, and of autologous LAK effectors generated at the time of complete remission (CR). In 12 of 23 ALL cases (52%), the blasts were susceptible to normal LAK cells (> 15% lysis) and ten of them achieved a CR. Of the remaining 11 LAK-resistant cases, seven obtained a CR. No correlation was found between susceptibility to LAK activity, cytomorphology, immunophenotype, CR duration and survival. Eighteen of the 26 AMLs tested (70%) were susceptible to normal LAK cells, and nine of the 13 cases studied (70%) were also lysed by autologous LAK effectors generated at CR. No clearcut correlation was observed between blast sensitivity to normal LAK cells and morphologic cytotype, though a higher incidence of resistant cases was observed in the M4 subgroup. All AMLs susceptible to normal LAK cells but one achieved a CR, while this occurred only in three of the eight resistant cases (p = 0.004). The median survival and event-free survival duration in the resistant patients were significantly shorter (p = 0.03 and p = 0.02, respectively) compared to those of the susceptible patients. In ten ALL and in six AML, which at presentation displayed less than 10% circulating blasts, the susceptibility of the leukemic population to normal and autologous LAK effectors could be tested, both at diagnosis and at remission. All cases but one were resistant to autologous LAK cells generated at diagnosis, while at CR, seven cases (four ALL and three AML) became susceptible to autologous LAK cells (p = 0.01). The remaining nine were resistant to both allogeneic and autologous LAK effectors. Taken together, these findings suggest that in AML, but not in ALL, the LAK cell compartment may play a role in the clinical course and overall outcome of the disease.

Adolescent↗

Expression of adhesion molecules on acute leukemic blast cells and sensitivity to normal LAK activity.

Antigenic expression of CD54 and CD58 adhesion molecules was investigated on leukemic blast samples from ten patients with acute lymphoblastic (ALL) and 14 with acute myeloblastic (AML) leukemia. The mean intensity of fluorescence (MIF) was calculated and correlated with sensitivity of blast cells to the lytic activity of allogeneic lymphokine-activated killer (LAK) cells. CD54 antigen was expressed in all AML cases with an MIF of 11.2 while in ALL, though present in the majority of cases, it was absent in one case and expressed in less than 30% of blasts in two others, with an overall MIF of 3.0. CD58 expression was similar in both groups of patients, with an MIF of 7.6 in ALL and 7.0 in AML. In addition, in six of the ten ALL cases and in two of the 14 AML cases, leukemic blasts proved to be "resistant" to the cytotoxic activity of normal allogeneic LAK effectors. In these "LAK-resistant" patients, the CD54 antigenic expression was lower (p = 0.03) than in "LAK-sensitive" patients with an MIF of 1.7 vs 4.9 in ALL and 1.35 vs 12.9 in AML cases. Finally, blocking of CD54 and/or CD58 receptors on leukemic blasts resulted in a slight reduction of 51Cr release. Findings suggest that CD54 is differently expressed on myeloid and lymphoid blasts and that there is a correlation between CD54 MIF and susceptibility of blasts to the LAK activity.

Antigens, CD↗

Fludarabine: an active agent in the treatment of previously-treated and untreated low-grade non-Hodgkin's lymphoma.

BACKGROUND: Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with a promising therapeutic activity in the lymphoproliferative disorders. PATIENTS AND METHODS: We performed a phase II study with this drug in previously untreated and treated patients with resistant and/or relapsed low-grade non-Hodgkin's lymphoma (LG-NHL) to determine its response rate. Twenty-one patients were treated at a dosage of 25 mg/m2 per day for 5 consecutive days. RESULTS: Of the 21 patients, 3 achieved complete responses (CR) and 11 partial responses (PR). In addition, three patients obtained minor responses, and the remaining 4 showed no benefit from the treatment. An increased response rate was achieved in 8 untreated patients in which 3 CR and 3 PR were documented. Furthermore, 4 of the 5 patients showing a leukemic blood picture experienced significant reductions of lymphocyte count and 2 patients with macroglobulinemic lymphomas experienced significant reductions of the IgM monoclonal component from 7.8 and 5.9 g/100 mL to 1.0 and 1.1 g/100 mL, respectively. The toxicity on platelets was negligible. The major toxic effects observed were neutropenia (62%) and infections and/or febrile episodes (19%) that were fatal to only one patient. CONCLUSIONS: In consideration of its significant activity, the role of FLU needs to be further evaluated in the management of pretreated and untreated patients with LG-NHL.

Adult↗

Fludarabine in patients with advanced and/or resistant B-chronic lymphocytic leukemia.

In this study, we evaluated the efficacy of fludarabine (FLU), an adenine nucleoside analogue, in 35 previously treated patients with advanced and progressed B-cell chronic lymphocytic leukemia (B-CLL) and in 6 at diagnosis. All patients were treated at a dose of 25 mg/m2 per day for 5 consecutive days (mean number of courses was 5, with a range from 4 to 6). The majority of patients experienced a beneficial effect on hematological parameters. In particular, a remarkable reduction of lymphocyte count together with an increase of neutrophils and platelets was observed. The overall response rate was 42% with 1 complete response and 16 partial responses. Ten patients achieved minor responses and the remaining 14 showed no benefit from treatment. An increased response rate was achieved in 6 untreated patients who showed an overall response rate of 67% (4/6). The major complications observed were neutropenia (66%) and febrile episodes (44%) that were generally infection-related and were fatal in 3 cases. Because we were dealing with patients whose disease was advanced and/or resistant to treatment, the overall results may be considered encouraging with acceptable toxic reactions not superior to those frequently observed with polychemotherapy.

Adult↗

High complete remission rate in hairy cell leukemia treated with 2-chlorodeoxyadenosine.

2-Chlorodeoxyadenosine (2-CdA), a purine nucleoside, has been shown to be remarkably effective in the treatment of patients with hairy cell leukemia (HCL). We hereby report on the results achieved in 26 HCL patients treated with one single course of 2-CdA at a dose of 0.1 mg/kg daily for 7 days continuous infusion. Twenty-four were males and 2 females, with a median age of 56 years; all but 5 had been previously treated with Interferon-alpha (IFN-alpha). All cases are fully evaluable for their clinical and hematological response. Twenty of them (77%) achieved a complete remission and 6 a partial remission; two of the latter progressed after 6 and 12 months, respectively. The median duration of response was 13.8 months, ranging from 7 to 22 months from the end of therapy. Circulating hairy cells and spleen enlargement, when present, disappeared within 2 weeks after completing treatment; furthermore, a rapid normalization of soluble Interleukin-2 receptor serum levels was observed in all complete responders but one, and in 2 of the 6 partial responders. A significant lymphocytopenia was observed in almost all patients, whilst a severe neutropenia (< 500/microliters) was registered mainly in the 10 patients who had less than 1,000/microliters neutrophils when treatment was started; the hemoglobin and platelets were marginally affected in only a few cases. Eight of the 10 patients who developed severe neutropenia experienced fever; in 4 of them it was short-lived (24 hours) and apparently not infection-related, while the remaining 4 probably had an infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Results in hairy-cell leukemia patients treated with alpha-interferon: predictive prognostic factors.

Fourty-four evaluable patients with hairy cell leukemia (HCL) were treated with human lymphoblastoid alpha-interferon (alpha-IFN), at a dose of 3 x 10(6) Units a day for 12-18 months while 18 of them continued to receive a three times per week schedule at the same dose as maintenance treatment. Eighteen percent of patients achieved complete response, 64% partial response, and 18% minor response with a median duration of 37.5, 22.9 and 3.5 months respectively. Twenty patients (45%), all partial or minor responders, subsequently had progression of the disease. The progression occurred more frequently in patients who presented at diagnosis with a hairy-cell index value > 0.50 than in those who presented with a hairy-cell index < 0.50: 14/26 (54%) versus 2/11 (18%) respectively. In addition, the progression rate was more evident in "non-maintained" than in "maintained" patients: 16/26 (61.5%) versus 4/18 (22%). Restarting alpha-IFN treatment in 16 of the 20 progressed patients proved effective only in 9 of them. From these findings it appears that a low hairy-cell index at diagnosis correlates favorably with a good hematological response. Furthermore, continuous therapy with alpha-IFN seems very useful in reducing the progression of the disease, in particular in patients with a very high hairy-cell index at diagnosis.

Adult↗

Serum soluble interleukin-2 receptor levels in hairy cell leukemia: correlation with clinical and hematological parameters and with alpha-interferon treatment.

The soluble Interleukin-2 Receptor (sIL-2R) serum levels were assessed in 42 patients with Hairy-Cell Leukemia (HCL) at diagnosis and after alpha-Interferon therapy and correlated with spleen size, peripheral hematological values, hairy cell index (HCI) and clinical response. Serum sIL-2R levels were significantly increased in all HCL patients, particularly in those with a higher HCI (> 0.50) and in non-splenectomized patients. Among the 26 HCL patients who were studied before and after 12 months of alpha-IFN treatment, 16 normalized the sIL-2R level and 10 did not. Our findings suggest that sIL-2R levels in HCL patients correlate with the splenic and bone marrow tumor burden as assessed by HCI. In addition patients with low levels of sIL-2R at diagnosis appear to have a better chance of achieving a good clinical response.

Biomarkers, Tumor↗