Search

Background and Objectives: To investigate the feasibility of peripheral blood stem cell (PBSC) transplantion in patients with high-risk chronic lymphocytic leukemia (CLL) in remission after fludarabine therapy, the clinical impact of minimal residual disease (MRD) monitoring and the immunologic reconstitution after transplantation., Design and Methods: Twenty CLL patients, in clinical complete remission (CR) after fludarabine, were offered an unmanipulated PBSC transplant and were longitudinally monitored for MRD and immunologic reconstitution., Results: Due to unsatisfactory PBSC collection, 4 patients received bone marrow cells. All patients engrafted. Two patients died, one due to infection and one because of another neoplasia. Thirteen patients are at present in clinical CR after a median follow-up of 17 months and 18 patients are alive with a survival probability of 0.87 (+/-0.04) at 52 months after transplant. Fifteen patients had a molecular remission. Three of them showed a molecular relapse 16-28 months after autograft, followed by a clinical relapse 10-16 months later. Three of the four patients who remained persistently rearranged could be revaluated over time and showed an immunologic relapse 11-26 months after transplant; two of these had a clinical relapse 12 and 7 months later. A marked and persistent impairment of both the B- and T-immunologic compartments was recorded in the horizontal follow-up., Interpretation and Conclusions: Unmanipulated PBSC autograft is a feasible procedure that produces prolonged molecular remissions in high-risk CLL patients. Persistence or reappearance of a molecular signal after engraftment is predictive of subsequent immunologic and clinical CLL recurrence. The long -lasting impairment of the host immune repertoire after fludarabine followed by autograft has to be taken into account in the patients' management.

The clinical trial has to be rigidly followed because it identifies a uniform clinical behaviour, which has to be adopted by the different physicians carrying out the test. The life cycle of the clinical trial is therefore based on a planning and definition phase, a next experimental phase connected with its diffusion to the involved centres and finally an evaluation phase of the results. An information system, which supports the users in the different phases of the clinical trial life cycle, has to take into account the different characteristics of each phase. The aim of this paper is to illustrate the role of WF technology as a component of an information system which supports the life cycle of a clinical trial also on the basis of the experience of the Italian Group for Haematological Disease of Adults (GIMEMA).

Background and Objective: Autologous transplantation is a better treatment for multiple myeloma (MM) than chemotherapy, but uncertainty remains about patient selection, optimal timing of autograft, conditioning regimen, need for a second autograft, and role of maintenance. To provide partial answers to these questions we assessed the results of autologous transplantation in a large cohort of patients whose data were reported to the GITMO registry., Design and Methods: We retrospectively analyzed data from 290 patients with MM (M = 150; F = 140; median age 52 years, range 19-70; stage I = 34, stage II = 75, stage III = 167) reported to the GITMO. At the time of autograft, 20% were in CR, 66% in PR, while the remaining had non-responsive or progressive disease. Median time between diagnosis and transplant was 16 months (1-90). Seventy-two patients (26%) had been planned to receive a double autograft, but this was actually done in only 35 (12%). The conditioning was chemotherapy in 90%. Peripheral blood was the only source of stem cells in 94%, and purging was applied in 10% of cases. For statistical analysis of data, differences between patient subsets were analyzed using the chi-square test, while the Kaplan-Meier method was used to estimate event-free survival (EFS) and survival (OS) probabilities. The Cox model was used for multivariate analysis., Results: Following the autograft, 116 patients (40%) were in CR, 144 (50%) in PR, 24 (8%) did not respond or progressed and 6 (2%) died before response evaluation. Transplant-related mortality occurred in 3%. At a median follow-up of 23 months, 223 (77%) patients are alive, 71 (24%) of them in CR, and 67 (23%) patients have died at a median time of 20 months (0-70). OS and EFS at 6 years are 47% and 28%, respectively, but the EFS curve shows no plateau. In multivariate analysis, age, beta2-microglobulin level and status at transplant emerged as significant prognostic factors for both OS and EFS, while time from diagnosis to transplant showed borderline significance., Interpretation and Conclusions: Based on the prognostic factors identified in multivariate analysis, we were able to assess the weight of a single prognostic factor or their combinations on transplant outcome. We also calculated the probability of OS and EFS by the number of factors at the time of autograft. Autologous transplantation is a safe and effective procedure, not only in sensitive patients, but also in resistant cases, provided they are <55 years of age and have low beta2-microglobulin. It should be applied early after the diagnosis of multiple myeloma, following the delivery of brief primary chemotherapy.

Purpose: Several studies have been conducted in Italy to assess the activity of recombinant interleukin-2 (rIL-2) in patients with relapsed-refractory acute myelogenous leukemia (AML) and in AML patients in second complete remission (CR) who are not eligible for standard therapy. We report here the updated results of those studies., Patients and Methods: Since 1988, a total of 24 patients with relapsed-refractory AML and < or = 30% bone marrow blasts (median blastosis, 15%), who were not suitable for further chemotherapy, were treated with a daily dose-escalating protocol of rIL-2 (8-18 x 10(6) IU/m2 x 5 days) by continuous intravenous infusion with a 72-hour rest period between each cycle. Patients achieving a response to induction therapy received subcutaneous maintenance rIL-2 therapy at lower doses for 5 days/month. Based on these encouraging results, a prospective randomized trial was initiated by the Italian cooperative groups GIMEMA (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto) and AIEOP (Associazione Italiana Ematologie e Oncologia Pedietrica) to assess the efficacy of this rIL-2 regimen in AML patients in second CR. Of 264 AML patients enrolled, 146 patients (55%) achieved a second CR in response to mitoxantrone, etoposide, and cytarabine; 32 patients who were not eligible for transplantation were randomized to rIL-2 (15 patients) or no treatment (17 control patients). Accural goals were never reached, however, due to low recruitment., Results: In the pilot study, 13 patients (54%) obtained a CR, which persists in eight patients with a median follow-up of 64 months (range, 1-110 months) on maintenance rIL-2. In the randomized study, a trend in favor of improved disease-free survival was observed in the rIL-2 arm., Conclusions: Encouraging results have been obtained with rIL-2 therapy in AML patients with relapsed-refractory disease and limited blastosis and in patients in second CR. These results have prompted a large, multicenter, randomized study to evaluate the efficacy of high-dose rIL-2 therapy in AML patients with advanced disease but limited blastosis in relapse following cytoreductive chemotherapy or autologous transplantation.

Reverse-transcription polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene may predict relapse in acute promyelocytic leukemia (APL) patients in hematologic complete remission (CR). We have prospectively studied by RT-PCR 15 PML/RAR alpha+ APL patients undergoing autologous bone marrow transplantation (ABMT) in second CR. The median time of first CR duration was 12 months (range, 6 to 40). All patients were reinduced with all-trans retinoic acid (ATRA), followed in 12 of 15 cases by mitoxantrone and Ara-C as consolidation. Fourteen patients received the BAVC (BCNU, Ara-C, m-AMSA, and VP-16) schedule as conditioning regimen. Unpurged marrows were collected immediately before conditioning treatment, analyzed by RT-PCR, and reinfused at median of 2 months (range, 2 to 7) from the achievement of second CR. Seven patients were PCR+ and eight PCR for PML/RAR alpha in their pretransplant marrows. All seven patients of the former group remained PCR+ during the follow-up and relapsed at a median time of 5 months (range, 2 to 9) from ABMT and 9 months (range, 4 to 14) from second CR. Of the eight PCR- patients, all remained PCR- during the follow-up controls. One patient relapsed at 10 months from ABMT, one died of a secondary (PML/RAR alpha-) leukemia, and six are in hematologic and molecular remission at a median time of 28 months (range, 15 to 60) after ABMT and 32 months (range, 17 to 62) from second CR. Our results indicate that, in APL patients in second CR, ABMT with PML/RAR alpha- marrow cells is likely to result in prolonged clinical and molecular remissions. Conversely, patients who test PCR+ after reinduction necessitate the use of alternative aggressive approaches, including unrelated allogeneic transplant.

Background and Objective: Allogeneic bone marrow transplantation remains the only potentially curative treatment for CML, but more than 70% of patients will be ineligible for allogeneic marrow transplant either because they do not have a suitable HLA-matched related or unrelated donor or because they are more than 50 years old. Several experimental and clinical findings support a role for autologous stem cell transplantation (ASCT) in CML. It has been suggested that in the early phase following autografting the Ph-negative clone has a proliferative advantage over the Ph-positive clone. We hypothesized that post-transplant GM-CSF administration could reactivate the functional activity of quiescent normal progenitors and prolong the duration of the post-transplant proliferative advantage of Ph-negative over Ph-positive progenitors. In order to evaluate the effect of post-transplant GM-CSF administration, a pilot clinical study was performed in which CML patients resistant to IFN-alpha therapy were autografted with unmanipulated marrow or blood cells and given prolonged GM-CSF therapy post-transplant., Methods: Five adult CML patients conditioned with the BAVC regimen were reinfused with either marrow (n = 2) or blood (n = 3) cells and given granulocyte-macrophage colony-stimulating factor (GM-CSF). Recombinant GM-CSF was initially administered at standard dosage (5 micrograms/kg/day) until a white blood cell count > or = 2 x 10(9)/L was achieved on two consecutive examinations, and thereafter at a low dose (1 microgram/kg/day) for 5 to 9 months. On a weekly basis, GM-CSF was discontinued and hydroxyurea (1,000 mg/d) was given for two days., Results: Evidence of trilineage engraftment was observed in all cases. At autografting, 3 out of the 5 patients revealed 8-9% Ph-negative metaphases. During the initial phase of hematopoietic regeneration, direct cytogenetic analysis revealed 81% and 100% Ph-negative metaphases in two cases; nonleukemic hematopoiesis progressively decreased and was no longer detectable at +9 months. One patient showed cyclic Ph-negative hematopoiesis that appeared 3 months following autografting and peaked at +4 and +8 months. The fourth patient showed a low percentage (20%) of Ph-negative metaphases 1 month after ASCT, followed by a significant expansion of nonleukemic hematopoiesis, which could be detected up to month +13. No evidence of Ph-negative hematopoiesis could be detected in one patient. Three patients are in chronic phase 28, 30 and 31 months after autografting, respectively, and two patients evolved into blast crisis., Interpretation and Conclusions: This pilot study demonstrates that combined GM-CSF and hydroxyurea therapy seems to be effective in inducing and/or prolonging a transient period of Ph-negative hematopoiesis. The late appearance of Ph-negative hematopoiesis detected in two patients suggests an antileukemic activity of the combined GM-CSF/hydroxyurea therapy rather than an antileukemic effect of the conditioning regimen.

This report summarizes indications and results of autologous bone marrow transplantation (ABMT) performed in childhood acute myeloid leukemia (AML) in Italy since 1984. A total of 158 patients have been reported from 12 teams to the AIEOP-BMT Registry: 110 have been autografted in first complete remission (CR) and 48 in second remission. Several conditioning regimens have been utilized, mainly consisting of BAVC (an original polichemotherapy schedule, BCNU, mAMSA, VP-16 and Ara-C) (63 cases) and of total body irradiation (TBI) plus Melphalan (33 cases): other 28 patients received different TBI-including regimens, and 34 received various chemotherapy regimens (Busulfan plus cyclophosphamide +/- VP-16, Busulfan plus Melphalan, Melphalan alone). Projected event-free survival (EFS) for patients autografted in first CR is 41.4% (S.E. 5.5%) at 7 years, with a total of 53 patients in continuous CR. EFS is better in patients receiving a TBI-including regimen: 78.8% versus 27.2% (p = 0.0001). In particular, results obtained in a subgroup of 21 cases receiving TBI + melphalan and purged marrow are particularly encouraging, with a EFS > 85% projected a 7 years. The overall EFS in second CR is 41.5% at 7 years, and no difference have been observed after a TBI-including regimen or after a chemotherapy regimen, being EFS 43.1% and 39.3% for these 2 groups respectively. A total of 11 transplant-related deaths occurred, with 5 patients (4.5%) dead in first CR and 6 (12%) dead in second CR within 100 days from transplant. From these data, ABMT is confirmed to represent an effective treatment for AML after first relapse, while the encouraging results obtained in first CR with TBI-including regimens should be confirmed with a longer follow up and a larger number of patients.

Since 1984 we have autografted a total of 60 patients with AML in second complete remission (CR) utilizing the BAVC (BCNU, amsacrine, vepesid, cytosine-arabinoside) conditioning regimen and unpurged marrow. Projected disease-free survival (DFS) probability in 42% at 10 years. Autografting was performed at a median interval of 2 months (range 1-13) from second CR. The median duration of first CR was 14 months (range 1-43) and lasted < or = 12 months in 27/60 patients. Three early deaths (5%) occurred, 30 patients relapsed after a median of 6 months from transplant (range 2-28) and, of the remaining 27 patients, 26 are in continuous CR (CCR) after a median follow up of 60 months (range 6-122), while the last patient committed suicide 7 years after ABMT when she was still in CCR. A first CR duration > 12 months is correlated with a significantly better overall survival probability (61 vs 25%, P = 0.02), while no factors influence DFS. Outcome of patients who relapsed after autografting has been analyzed separately; a longer overall survival after relapse is correlated with a longer duration of the second CR (62% at 34 months for patients who relapsed after > 12 months from the autograft vs 5% for the others, P = 0.001). These results confirm that AML patients autografted in second CR with BAVC regimen and unpurged marrow have the possibility of becoming long-term DFS and can therefore be cured.

High dose therapy followed by infusion of autologous bone marrow has become a major treatment option for an increasing number of poor prognosis non-Hodgkin's lymphoma (NHL) patients. In our study we analyzed the outcome of autologous bone marrow transplantation (ABMT) in 44 high grade NHL patients transplanted at our institution between 1985 and 1992. Median age was 31 years (range 12-61); nineteen were in partial remission (PR) after first line chemotherapy and 25 in sensitive relapse (SR). Of the 25 patients transplanted in SR, 14 relapsed after a median time of 5.5 months (range 1-26), 8 are in complete remission after a median follow up of 41.5 months and three died from toxicity. Of the 19 patients grafted in PR, 11 are alive and progression free after a median follow up of 52 months, while 8 relapsed at a median time of 5 months. The overall progression free survival (PFS) projected at 6 years is 35% with a 47% PFS for patients transplanted in PR and 28% for patients in SR. In conclusion, high dose therapy and ABMT has achieved widespread use as salvage therapy for patients with relapsed/refractory high grade NHL. In particular, our experience confirms that myeloablative treatment is a safe and well tolerated procedure for patients in PR, that may be easily applied as early salvage therapy without major toxicities.

The prognosis of patients in blast crisis of chronic myelogenous leukemia treated with conventional polychemotherapy is extremely poor. Autologous blood stem cell transplantation has been proposed by several authors, and the possibility of achieving a second chronic phase (CP), albeit very short lived, has been reported. In our study, we evaluated the feasibility and efficacy of a double sequential autograft program utilizing two different conditioning regimens. Nine patients underwent the first autograft, but only three were eligible for the second because of one early death, four relapses and one patient who underwent mismatched alloBMT. Of the three patients receiving the second graft, we observed 2 toxic deaths and one relapse six months after transplantation. We conclude that our experience with double autograft in this phase of the disease is very disappointing. since it was associated with prohibitive toxicity in the absence of any advantages in terms of survival for these patients.

Since 1988 we have treated a first group of 14 patients with recombinant interleukin-2 (rIL-2), which was previously published, and 6 other consecutive patients affected by refractory or relapsed acute myelogenous leukemia (AML) with >5% and < or = 30% bone marrow blasts, but not suitable for further chemotherapy. The rIL-2 schedule consisted of four 5-day high-dose cycles administered by continuous infusion with a 72-hour rest period between each cycle. Patients who achieved a response received a lower dose of subcutaneous rIL-2 maintenance treatment administered for 5 days every month. Following high-dose rIL-2, 11/20 patients (55%) obtained a complete remission (CR). Six remain in persistent CR after a median follow-up time of 50 months (9, 33, 49, 51, 52, 87 months, respectively); the length of remission is the longest in the natural history of the disease for each individual patient. One patient with stable disease at the end of rIL-2 induction is alive and well, with a stable number of blasts in the bone marrow, 18 months later. These 7 patients continue maintenance treatment with subcutaneous rIL-2. Close clinical and laboratory monitoring reveal that side effects are acceptable and no toxic deaths have been recorded. This update confirms the feasibility and antileukemic activity of high dose rIL-2 in advanced AML patients with limited disease, and suggests a potential clinical role of prolonged rIL-2 maintenance treatment.

Seven children with a primary myelodysplastic syndrome were seen at our center over a 9-year period. Two presented with refractory anemia, three with refractory anemia with excess of blasts, and two with refractory anemia with excess of blasts in transformation. All children received supportive therapy, including blood transfusions in five of them. Three patients developed acute myeloid leukemia and were treated with intensive chemotherapy, followed by allogeneic or autologous marrow transplantation in the two responders. All three died of either infection or progressive disease. The other four patients are still alive a median of 71 months (range 38-130) after diagnosis. These results confirm the difficulties in managing patients with myelodysplastic syndromes.

Significant clinical responses obtained with interleukin 2 (IL-2) in solid tumors such as renal cell cancer and malignant melanoma prompted the use of this immunomodulatory drug to verify its activity in hematological malignancies. Several preclinical experiments showed an activity of IL-2 against leukemic cell lines in cultures, particularly in acute myeloid leukemia (AML), while only episodically a proliferative stimulus of IL-2 on the growth of leukemic blasts has been observed. Based on these preclinical studies, in the past five years several phase I-II clinical trials have verified IL-2 activity in AML in advanced phase, both in patients with active disease and in patients in further complete remission (CR). Data obtained are difficult to evaluate due to the low number and the heterogeneity of patients treated, but encouraging results have been reported in patients with "limited" disease (bone marrow blastosis < 30%), showing an antileukemic activity of IL-2 alone. Different international phase III trials are ongoing in AML patients in I CR after autologous bone marrow transplantation (Roussel-Uclaf, Romainville, France) and in II CR after conventional chemotherapy (Roche SpA, Milan, Italy) to verify the efficacy of IL-2 in reducing the risk of relapse and prolonging disease-free survival.

Unlabelled: BACKGROUND AND METHODS. The usefulness of hematological parameters provided by the Technicon H*1 was investigated for the diagnosis of acute lymphoblastic leukemias (ALL) and for the identification of blast cells in peripheral blood samples., Results and Conclusions: When automated blast detection was compared with microscopic examination in 62 samples with 4-98% morphologically recognizable lymphoblasts on peripheral blood smears, a false-negative result occurred in 28% (17/62) of the ALL cases. However, in 14 of these 17 false-negative cases the H*1 generated an output listing that would require microscopic evaluation in any event. The H*1 output listing interpretation (based on abnormal leukograms, blast flags and bicytopenia) led us to suspect the presence of ALL in 76% (47/62) of the cases. Three ANLL were recognized as ALL. In three out the 62 ALL, the H*1 output listing interpretation missed identify a leukemic process. In most cases (77%) we noted a characteristic deformation of the mononuclear population profile in the baso/lobularity display, and the cloud of analytical points was shifted toward to the left, in keeping with the presence of a large number of hypodense nuclei.

In an attempt to prolong disease-free survival in children with acute leukemia, we tested the feasibility of interleukin-2 (IL-2) administration after an autologous bone marrow transplantation (ABMT). We report the clinical and biological data obtained in three children with acute myelocytic leukemia (AML) in second complete remission (CR) and in seven children with acute lymphocytic leukemia (ALL) in second or subsequent CR, who received IL-2 at a median interval of 78 days (range 38-125) from ABMT. Patients were treated with 1-2 cycles of IL-2 given by continuous infusion over a 5-day period using a daily escalating protocol, from 100 micrograms/m2 per day to the maximum tolerated dose, followed after 3 weeks by low-dose IL-2 for 5 days monthly over a 6-h infusion on an out-patient basis. Side effects greater than grade 2 (WHO system), consisting of thrombocytopenia, fever, cutaneous rash, nausea and vomiting, diarrhoea were common during the high-dose IL-2 cycles, but resolved 24-48 h after stopping IL-2. Only one patient developed liver toxicity (grade 3, WHO) on day +3 of the first cycle which prompted us to stop the administration of IL-2. An increase in lymphocytes and eosinophils was also observed. IL-2 treatment was followed by a normalization of NK function and by the generation of a high proportion of endogenous LAK cells. All seven ALL patients relapsed at a median of 5 months (range 1-23). Two AML patients relapsed at 1 and 11 months, while the other is still in continuous CR at 23 months after IL-2 treatment. Our IL-2 schedule for treatment of leukemia in children after ABMT is thus feasible but its efficacy requires further investigation.

In this paper we review some of the preclinical findings which have led us to believe that immunotherapy with interleukin 2 (IL2)/lymphokine activated killer (LAK) cells may be a feasible approach in the management of acute myeloid leukemia. The main clinical and biological results so far obtained with IL2 treatment, and the currently ongoing protocols and strategies are discussed.

We report data from an Italian survey on ABMT in 93 AML children less than 14 years in 1st or 2nd remission performed in 15 Centers. Different conditioning regimens have been employed: BAVC, an original schedule of chemotherapy; TBI plus Cy and/or other drugs (TBI + CHT); other high dose chemotherapy schedules (HD CHT). 62 patients have been transplanted in 1st CR; 38 have been conditioned with BAVC, 16 with TBI + CHT and 8 with HD CHT. Relapses were 21 in the BAVC group (DFS = 35% at 66 months), 5 in the TBI group (DFS = 61% at 48 months) and 5 in the HD CHT group; overall DFS is 39% at 66 months. 31 patients have been transplanted in 2nd CR; 14 were conditioned with BAVC and 16 with TBI + CHT; 6 patients relapsed in the first group, DFS is 56% at 50 months; in the second group 2 early deaths and 3 relapses occurred, DFS is 65% at 65 months. 1 patient in 2nd CR, conditioned with HD CHT, died during aplasia. Overall DFS is 59% at 65 months. Although no final conclusions concerning ABMT in AML children may be drawn from this retrospective study because of heterogeneity of population and methods, results obtained in 2nd CR are clearly better to those obtained with standard chemotherapy alone, confirming the role of ABMT in this high risk category of patients.

Five patients with lymphoid blastic transformation of chronic myeloid leukemia have been treated with IL2 associated with Vincristine (VCR) plus Prednisone (PDN). Our study indicates that IL2 may be employed in the management of this disease without excessive toxicity at the higher doses in hospitalized patients and at the lower doses as outpatients. Concerning the therapeutic efficacy, our preliminary results indicate that IL2 might be useful in enhancing the chemosensitivity of the leukemic blasts. It remains to be seen if this will result in a rapid return to the CP and in a prolongation of survival.

The authors have evaluated the influence of some obstetric events (type and duration of labour and method of delivery) and some pharmacological factors (oxytocic drugs during labour, local infiltration, duration of general anaesthesia, oxytocic drugs and/or ergot derivatives during puerperium) on frequency of breast-feeding at the time of discharge from hospital. About 57% of 356 newborns were breast-fed (wholly or prevalently) at discharge from the "A. Gemelli" University Hospital in Rome, during two months period (march-april 1981). The results showed that all those conditions requiring medical and paramedical action, either instrumental or pharmacological (such as: induced labour, prolonged labour, operative delivery either vaginal or abdominal, particularly in emergency; use of local infiltration; use of oxytocic drugs during labour, particularly for induction; prolonged general anaesthesia in caesarean section) may have an unfavorable effect, nearly always significant, on breast-feeding. According with these results, the Authors suggest the following measures for breast-feeding promotional programme: modification of neonatal routine care to promote an earlier mother-infant interaction during lying-in; limitation of avoidable obstetric procedures and of drugs giving to mothers; a better understanding of pharmacokinetics, both in mothers (placentar passage of drugs and through milk) and in newborns during labour, delivery and puerperium.

We performed 56 HDIVG administrations in adults (26) and children (30) affected by idiopathic thrombocytopenic purpura with two different schedules: a five-day course at 400 mg/kg/d and a "bolus" 1 gr/kg. Forty-five cases were treated in preparation for surgical operations and eleven for bleeding episodes. Response to the five-day course in adults was good in 3/24, fair in 13/24, poor in 8/24, while in children it was good in 14/26, fair in 9/26, poor in 3/26. The difference between adults and children is statistically significant. None of the responder patients submitted to surgical operation needed platelet infusions during surgery. Response to the "bolus" schedule (6 cases) in adults was poor in 1 case and good in the other one, and in children, fair in 3 cases and good in the other one. In responder patients treated for bleeding episodes we obtained clinical improvement with hemorrhage arrest. In adults the treatment was well-tolerated, while in children we observed 3/30 mild side effects and 1/30 important side effect.

In 7 splenectomized and 21 non splenectomized pediatric patients with hereditary spherocytosis (HS), red cell size and hemoglobin concentration distribution (erythrograms) demonstrated the size and chromia degree of red cell populations. The H-1 Technicon graphic reports obtained in the analysis of HS blood showed a remarkable shift of the Hb concentration histograms to the right end of the x-axis, revealing the presence of a high percentage of hyperchromic red cells. The opposite shift was noted for volume histograms. Graphic findings were quantitated by a computerized program of the H-1 Technicon system. These data have enabled us to determine the percentage of microcytic and normocytic hyperchromic RBC. In particular, non splenectomized HS patients showed an increase in microcytic and hyperchromic RBC twice as high as that of splenectomized patients (data computed by erythrograms). Moreover, there is a significant difference (5.6%, p less than 0.01) between splenectomized and non splenectomized patients in the microcytic hyperchromic RBC percentage (data computed by special volume/hemoglobin concentration mapping).